Acute Myeloid Leukemia (AML)Phase 1/2NCT04029688
A Study Evaluating the Safety, Tolerability, Pharmacokinetics and Preliminary Activity of Idasanutlin in Combination With Either Chemotherapy or Venetoclax in Treatment of Pediatric and Young Adult Participants With Relapsed/Refractory Acute Leukemias or Solid Tumors
A Phase 1/2 study testing Idasanutlin, Venetoclax and Cyclophosphamide in people with Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL), run by Hoffmann-La Roche at 14 sites in 6 countries.
Trial summary
This is a Phase I/II, multicenter, open-label, multi-arm study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of idasanutlin, administered as a single agent or in combination with chemotherapy or venetoclax, in pediatric and young adult participants with acute leukemias or… Read more about this study
- Who is it for?
- Ages 0 to 30 years
- Conditions the study is for
- Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), Neuroblastoma
- What is being tested?
- Idasanutlin, Venetoclax and Cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 14 sitesin 6 countries
- Study dates
- 27 Jan 2020to 6 May 2024
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- The participants ages are < 18 for part 1a, < 30 for Parts 1b. 2 and 3
- Study Part 1 (single-agent therapy dose escalation): histologically confirmed diagnosis of neuroblastoma or other solid tumor that has progressed or recurred despite standard therapy, and for which there is no therapy proven to prolong survival with an acceptable quality of life
- Study Part 1 (combination safety run-in), Study Part 2 (initial expansion), and Study Part 3 (additional expansion): histologically confirmed diagnosis of neuroblastoma, AML, or precursor-B ALL that has progressed or recurred despite, or is refractory to, standard therapy
- Adequate performance status: Participants <16 years of age: Lansky greater than or equal to (≥)50%; Patients ≥16 years of age: Karnofsky ≥50%
- Adequate end-organ function, as defined in the protocol
- For females of childbearing potential: agreement to remain abstinent, use contraception, agreement to refrain from donating eggs. Females must remain abstinent or use two methods of contraception with a failure rate of <1% per year during the treatment and follow-up period (variable depending on the combination agent) or in accordance with national prescribing information guidance regarding abstinence, contraception
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- For males: agreement to remain abstinent or use a condom, and agreement to refrain from donating sperm, with a female partner of childbearing potential or pregnant female partner, males must remain abstinent or use a condom during the treatment period and for follow-up period (variable, depending on the combination agent) or in accordance with national prescribing information guidance regarding abstinence, contraception
- Additional Inclusion Criteria for Participants with Solid Tumors (including Neuroblastoma)
- At least one evaluable or measurable radiological site of disease as defined by standard criteria for the participant's tumor type, or measurable bone marrow disease by morphology
- Adequate hematologic end-organ function, as defined in the protocol
- Tumor tissue from relapsed disease
- Additional Inclusion Criteria for Patients with Leukemia
- Bone marrow with ≥5% lymphoblasts by morphologic assessment at screening
- Available bone marrow aspirate or biopsy from screening
Who cannot join
- Primary Central Nervous System (CNS) tumors
- Symptomatic CNS metastases that result in a neurologically unstable clinical state or require increasing doses of corticosteroids or local CNS-directed therapy to control the CNS disease
- CNS3 leukemia
- Acute promyelocytic leukemia
- White blood cell count >50 × 10^9 cells/Liter (L)
- Down syndrome, Li-Fraumeni syndrome, history of severe aplastic anemia, or any known bone marrow failure predisposition syndrome
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- Burkitt-type acute lymphoblastic leukemia
- T-cell lymphoblastic leukemia
- Prior treatment with a MDM2 antagonist
- Prior treatment with venetoclax (if potential for enrollment in a venetoclax arm)
- Infection considered by the investigator to be clinically uncontrolled or of unacceptable risk to the participant
- Any uncontrolled medical condition or other identified abnormality that precludes the patient's safe participation in and completion of the study
- Systemic anticancer therapy within 28 days or 5 half-lives, whichever is shorter, prior to initiation of study treatment
- Treatment with monoclonal antibodies, antibody drug conjugates, or cellular therapy for anti-neoplastic intent within 30 days prior to initiation of study treatment
- I-131 meta-iodobenzylguanidine (MIBG) therapy within 6 weeks prior to initiation of study treatment
- Myeloablative therapy with autologous or allogeneic hematopoietic stem cell rescue within 100 days of study treatment initiation
- Immunosuppressive therapy for treatment of graft-versus-host disease within 2 weeks of study treatment initiation
- Radiotherapy within 3 weeks prior to study treatment initiation
- Specific restrictions are applicable for patients treated with drugs interacting with CYP2C8, CYP3A4, OATP1B1/B3, and P-gp
- Received anti-coagulant or anti-platelet agent within 7 days or 5 half-lives prior to study treatment initiation
- Underwent major surgical procedure within 21 days of study treatment initiation, or anticipate need for major surgical procedure during the course of the study
Trial locations and contacts
14 sites in 6 countries.
14 sites in 6 countries
United States5 sites
Arkansas Children's Hospital Research Institute
Little Rock, Arkansas, 72202
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Arnold Palmer Hosp-Children
Orlando, Florida, 32806
Lucile Packard Children's Hospital at Stanford University; Thoracic Oncology
Palo Alto, California, 94304
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
United Kingdom3 sites
Birmingham Children's Hospital
Birmingham, B4 6NH
The Royal Victoria Infirmary; Paediatric and Adolescent Oncology Unit
Newcastle upon Tyne, NE1 4LP
Royal Marsden Hospital; Pediatric Unit
Surrey, SM2 5PT
Spain2 sites
Hospital Sant Joan De Deu
Esplugues de Llobregas, Barcelona, 08950
Hospital Infantil Universitario Nino Jesus
Madrid, 28009
About this study
Official title: A Phase I/II, Multicenter, Open-Label, Multi-Arm Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Preliminary Activity of Idasanutlin in Combination With Either Chemotherapy or Venetoclax in the Treatment of Pediatric and Young Adult Patients With Relapsed/Refractory Acute Leukemias or Solid Tumors
This is a Phase I/II, multicenter, open-label, multi-arm study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of idasanutlin, administered as a single agent or in combination with chemotherapy or venetoclax, in pediatric and young adult participants with acute leukemias or solid tumors.
This study is divided into three parts: Part 1 will begin with dose escalation of idasanutlin as a single agent in pediatric participants with relapsed or refractory solid tumors to identify the maximum tolerated dose (MTD)/maximum administered dose (MAD) and to characterize dose-limiting toxicities (DLTs). Following MTD/MAD identification, three separate safety run-in cohorts in neuroblastoma, acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL) will be conducted to identify the recommended Phase 2 dose (RP2D) of idasanutlin in each combination, with chemotherapy or venetoclax. Part 2 will evaluate the safety and early efficacy of idasanutlin in combination with chemotherapy or venetoclax in newly enrolled pediatric and young adult participants in neuroblastoma, AML,and ALL cohorts at idasanutlin RP2D. Part 3 will potentially be conducted as an additional expansion phase of the idasanutlin combination cohorts in neuroblastoma, AML, or ALL for further response and safety assessment.
- Conditions
- Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), Neuroblastoma, Solid Tumors
- Being tested
- Idasanutlin, Venetoclax, Cyclophosphamide, Topotecan, Fludarabine
- Medical subject headings
- Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IdasanutlinDrug
Also called RG7388
Idasanutlin will be administered as an oral medication once daily on Days 1-5 of a 28-day cycle.
VenetoclaxDrug
Also called RG7601, GDC-0199, ABT-199
Venetoclax will be administered orally at the adult dose equivalent (adjusted by body weight) of 400 milligrams (mg) in participants with neuroblastoma and the adult dose equivalent of 600 mg in participants with leukemia.
CyclophosphamideDrug
Cyclophosphamide will be administered once daily on Days 1-5 of each 28-day cycle at 250 milligrams per meter squared of body surface area (mg/m^2) as an intravenous (IV) infusion.
TopotecanDrug
Topotecan will be administered once daily on Days 1-5 of each 28-day cycle at 0.75 mg/m^2 as an IV infusion.
FludarabineDrug
Fludarabine will be administered once daily on Days 1-5 of each 28-day treatment cycle at 30 mg/m^2 as an IV infusion.
CytarabineDrug
Cytarabine will be administered once daily on Days 1-5 of each 28-day treatment cycle at 2000 mg/m^2 as an IV infusion.
Intrathecal ChemotherapyDrug
All participants with leukemia, irrespective of arm, will receive intrathecal chemotherapy on Day 1 of each 28-day treatment cycle. Intrathecal chemotherapy will consist of either single-agent cytarabine or methotrexate, or a combination of methotrexate, cytarabine, and hydrocortisone, at appropriate age-based dosing as specified in the protocol.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation: Solid Tumors: Idasanutlin Single Agent | Experimental | Not described Receives: Drug: Idasanutlin |
| Neuroblastoma: Idasanutlin + Venetoclax | Experimental | Not described Receives: Drug: Idasanutlin; Drug: Venetoclax |
| Neuroblastoma: Idasanutlin + Cyclophosphamide + Topotecan | Experimental | Not described Receives: Drug: Idasanutlin; Drug: Cyclophosphamide; Drug: Topotecan |
| AML: Idasanutlin + Venetoclax | Experimental | Not described Receives: Drug: Idasanutlin; Drug: Venetoclax; Drug: Intrathecal Chemotherapy |
| AML: Idasanutlin + Fludarabine + Cytarabine | Experimental | Not described Receives: Drug: Idasanutlin; Drug: Fludarabine; Drug: Cytarabine; Drug: Intrathecal Chemotherapy |
| ALL: Idasanutlin + Venetoclax | Experimental | Not described Receives: Drug: Idasanutlin; Drug: Venetoclax; Drug: Intrathecal Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1a and 1b: Number of Participants With Adverse Events (AEs) and Severity of AEs Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5 (NCI CTCAE v5.0)
An AE is any untoward medical occurrence in participant administered a pharmaceutical product \& regardless of causal relationship with this treatment. An AE can therefore be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product. AEs were graded as per NCI CTCAE v5.0. Grade 1=Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated; Grade 2=Moderate; minimal, local or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living; Grade 3=Severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living; Grade 4=Life-threatening consequences/urgent intervention indicated; Grade 5=Death related to adverse event.
Measured: From screening up to 30 days after study treatment discontinuation (approximately 7 months)
Parts 1a and 1b: Number of Participants With Dose-Limiting Toxicities (DLTs)
DLTs were assessed for single-agent idasanutlin and idasanutlin in combination with chemotherapy or venetoclax. A DLT was defined as any AE that occurred during the DLT assessment window and was assessed by the investigator as related or possibly related to idasanutlin. An AE is an untoward medical occurrence in participant administered a pharmaceutical product \& regardless of causal relationship with this treatment. Following events were considered to be DLTs: any treatment-related death; elevation of serum hepatic transaminase; severe liver injury, in the absence of cholestasis or other causes of hyperbilirubinemia; any non-hematologic toxicity Grade ≥3; nausea, vomiting, and/or diarrhea if Grade 3 severity lasts > than 24 hours after initiation of supportive care measures or if Grade 4 or higher; hematologic toxicity; any related event that results in a dose delay beyond Day 42.
Measured: Cycle 1 (one cycle is 28 days)
Part 1b: Objective Response Rate (ORR) in Participants With TP53 Wild-Type (WT) Neuroblastoma Assessed According to International Neuroblastoma Response Criteria (INRC)
ORR was defined as the percentage of participants with complete response (CR) or partial response (PR) at any time during study treatment, on 2 consecutive occasions ≥ 4 weeks apart, as determined by the investigator per INRC. Primary tumor: CR = <10 millimeters (mm) residual soft tissue at primary site and complete resolution of meta-iodobenzylguanidine (MIBG) or fluorodeoxyglucose-positron emission tomography (FDG-PET) uptake at primary site. PR = ≥ 30% decrease in longest diameter of primary site and MIBG or FDG-PET uptake at primary site stable, improved, or resolved. Soft tissue \& bone metastases: CR = resolution of all disease sites; PR = ≥30% decrease in sum of non-primary target lesions, with no new lesions or ≥50% reduction in MIBG score or in number of FDG-PET-avid bone lesions; Bone marrow: CR = no tumor infiltration on reassessment.
Measured: From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)
Parts 2 and 3: ORR in Participants With TP53 WT Neuroblastoma Assessed According to INRC
ORR was defined as the percentage of participants with CR or PR at any time during study treatment, on 2 consecutive occasions ≥ 4 weeks apart, as determined by the investigator per INRC. Primary tumor: CR = <10 mm residual soft tissue at primary site and complete resolution of MIBG or FDG-PET uptake at primary site. PR = ≥ 30% decrease in longest diameter of primary site and MIBG or FDG-PET uptake at primary site stable, improved, or resolved. Soft tissue \& bone metastases: CR = resolution of all disease sites; PR = ≥30% decrease in sum of non-primary target lesions, with no new lesions or ≥50% reduction in MIBG score or in number of FDG-PET-avid bone lesions; Bone marrow: CR = no tumor infiltration on reassessment.
Measured: Up to approximately 29 months
Parts 2 and 3: Complete Remission Rate (CRR) in Participants With TP53 WT Leukemia
CRR was defined as the percentage of participants with morphologic complete remission (CR), complete remission with incomplete blood count recovery (CRi), or complete remission with incomplete platelet count recovery (CRp) within 2 cycles of study treatment. CR=Bone marrow blasts <5% (AML) and no evidence of circulating blasts, must be <1% (ALL); absence of blasts with Auer rods (AML); absence of extramedullary disease; absolute neutrophil count (ANC) >1.0*10^9/liter (L) [1000/microliter (µL)]; platelet count > 100*10^9/L (100,000/µL); independence of transfusions for a minimum of 1 week (AML and ALL). CRi= All CR criteria except for ANC <1.0*10^9/L[1000/µL] or insufficient recovery of platelet count <100* 10^9/L [100,000/µL] (AML and ALL). CRp=All CR criteria except for ANC >1.0*10^9/L[1000/µL]) or but with insufficient recovery of platelet (<100* 10^9/L [100,000/µL]) (ALL).
Measured: Up to Cycle 2 (cycle length=28 days) (approximately 8 weeks)
Parts 2 and 3: Minimal Residual Disease (MRD) - Negative Rate in Participants With ALL
MRD - negative rate was defined as percentage of participants with ALL who have an MRD value < 0.01%, as measured by next-generation sequencing (NGS), within 2 cycles of study treatment.
Measured: Up to Cycle 2 (cycle length=28 days) (approximately 8 weeks)
Secondary outcomes (24)
Part 1a: Clinical Benefit Rate (CBR) in Participants With Solid Tumors From SE Population Assessed According to Response Evaluation Criteria Version 1.1 (RECIST v1.1) or INRC
CBR was defined as the percentage of participants achieving confirmed CR, PR, or stable disease (SD) on 2 consecutive occasions ≥4 weeks apart during the total study period. Per RECIST, CR was defined as disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the baseline SOD. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference smallest sum on study. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference smallest sum on study (nadir), including baseline. Participants who had neuroblastoma were assessed by INRC. CR and PR per INRC were defined as outlined in the description for Part 1b: ORR outcome measure (OM).
Measured: From screening (maximum 28 days) up to Cycle 5 (cycle length=28 days)
Part 1b: CBR in Participants With Neuroblastoma From SE Population Assessed According to INRC
CBR=percentage of participants with CR, PR, or SD on 2 consecutive occasions ≥ 4 weeks apart per INRC. Primary tumor: CR=residual soft tissue at primary site is <10 mm, with complete resolution of MIBG/FDG-PET uptake; PR= ≥30% decrease in longest diameter (LD) of primary site, with stable/improved MIBG/FDG-PET uptake; SD=Insufficient shrinkage for PR/increase for PD. PD= >20% increase in LD from smallest sum \& minimum 5 mm increase in LD. Soft tissue \& bone metastases: CR=resolution of all disease sites; PR= ≥30% decrease in sum of non-primary target lesions, with no new lesions or ≥50% reduction in MIBG score or in number of FDG-PET-avid bone lesions; PD=new soft tissue lesions per CT/MRI or MIBG/FDG-PET avid bone site; SD=no sufficient change in non-primary lesions. Bone marrow: CR=no tumor infiltration on reassessment; PD=new tumor infiltration >5% or infiltration increased >2-fold with >20% tumor infiltration; SD=persistent infiltration at >5% without meeting other criteria.
Measured: From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)
Part 1b: CBR in Participants With TP53 WT Neuroblastoma Assessed According to INRC
CBR=percentage of participants with CR, PR, or SD on 2 consecutive occasions ≥ 4 weeks apart per INRC. Primary tumor: CR=residual soft tissue at primary site is <10 mm, with complete resolution of MIBG/FDG-PET uptake; PR= ≥30% decrease in longest diameter (LD) of primary site, with stable/improved MIBG/FDG-PET uptake; SD=Insufficient shrinkage for PR or increase for PD. PD= >20% increase in LD from smallest sum \& minimum 5 mm increase in LD. Soft tissue \& bone metastases: CR=resolution of all disease sites; PR= ≥30% decrease in sum of non-primary target lesions, with no new lesions or ≥50% reduction in MIBG score or in number of FDG-PET-avid bone lesions; PD=new soft tissue lesions per CT/MRI or MIBG/FDG-PET avid bone site; SD=no sufficient change in non-primary lesions. Bone marrow: CR=no tumor infiltration on reassessment; PD=new tumor infiltration >5% or infiltration increased >2-fold with >20% tumor infiltration; SD=persistent infiltration at >5% without meeting other criteria.
Measured: From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)
Part 1a: Duration of Response (DOR) in Participants With Solid Tumors From SE Population Assessed According to RECIST v1.1 or INRC
DOR was defined as the time from the first tumor assessment that supports a participant's objective response (CR or PR) to the time of PD or death from any cause (whichever occurs first), as determined by the investigator using RECIST v1.1 or INRC. Per PRECIST, CR was defined as disappearance of all target lesions. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference smallest sum on study (nadir), including baseline. Participants who had neuroblastoma were assessed by INRC. CR/PR/PD were defined per INRC as outlined in the description for the Part 1b: CBR OM.
Measured: From screening (maximum 28 days) up to Cycle 5 (cycle length=28 days)
Part 1b: DOR in Participants With Neuroblastoma From SE Population Assessed According to INRC
DOR=time from the first tumor assessment that supports a participant's objective response (CR or PR) to the time of PD or death from any cause (whichever occurs first), as determined by the investigator using INRC for participants with neuroblastoma. Primary tumor: CR=residual soft tissue at primary site is <10 mm, with complete resolution of MIBG/FDG-PET uptake; PR= ≥30% decrease in LD of primary site and MIBG or FDG-PET uptake at primary site stable, improved, or resolved; PD= >20% increase in LD from smallest sum \& minimum 5 mm increase in LD. Soft tissue \& bone metastases: CR = resolution of all disease sites; PR = ≥30% decrease in sum of non-primary target lesions, with no new lesions or ≥50% reduction in MIBG score or in number of FDG-PET-avid bone lesions; PD=new soft tissue lesions per CT/MRI or MIBG/FDG-PET avid bone site. Bone marrow: CR=no tumor infiltration on reassessment; PD=new tumor infiltration >5% or infiltration increased >2-fold with >20% tumor infiltration.
Measured: From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)
Part 1b: DOR in in Participants With TP53 WT Neuroblastoma Assessed According to INRC
DOR=time from the first tumor assessment that supports a participant's objective response (CR or PR) to the time of PD or death from any cause (whichever occurs first), as determined by the investigator using INRC for participants with neuroblastoma. Primary tumor: CR=residual soft tissue at primary site is <10 mm, with complete resolution of MIBG/FDG-PET uptake; PR= ≥30% decrease in LD of primary site and MIBG or FDG-PET uptake at primary site stable, improved, or resolved; PD= >20% increase in LD from smallest sum \& minimum 5 mm increase in LD. Soft tissue \& bone metastases: CR = resolution of all disease sites; PR = ≥30% decrease in sum of non-primary target lesions, with no new lesions or ≥50% reduction in MIBG score or in number of FDG-PET-avid bone lesions; PD=new soft tissue lesions per CT/MRI or MIBG/FDG-PET avid bone site. Bone marrow: CR=no tumor infiltration on reassessment; PD=new tumor infiltration >5% or infiltration increased >2-fold with >20% tumor infiltration.
Measured: From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)
Part 1a: Progression Free Survival (PFS) in Participants With Solid Tumors From SE Population Assessed According to RECIST v1.1 or INRC
PFS was defined as the time from initiation of study drug to the first documented occurrence of PD or death from any cause (whichever occurs first), as determined by the investigator using RECIST or INRC. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference smallest sum on study (nadir), including baseline. Participants who had neuroblastoma were assessed by INRC. PD per INRC: Primary tumor = >20% increase in LD from smallest sum \& minimum 5 mm increase in LD; Soft tissue \& bone metastases = new soft tissue lesions per CT/MRI or MIBG/FDG-PET avid bone site; Bone marrow = new tumor infiltration >5% or infiltration increased >2-fold with >20% tumor infiltration.
Measured: From screening (maximum 28 days) up to Cycle 5 (cycle length=28 days)
Part 1b: PFS in Participants With Neuroblastoma From SE Population Assessed According to INRC
PFS was defined as the time from initiation of study drug to the first documented occurrence of PD or death from any cause (whichever occurs first), as determined by the investigator using INRC for participants with neuroblastoma. Primary tumor: PD= >20% increase in LD from smallest sum \& minimum 5 mm increase in LD. Soft tissue \& bone metastases: PD=new soft tissue lesions per CT/MRI or MIBG/FDG-PET avid bone site. Bone marrow: PD=new tumor infiltration >5% or infiltration increased >2-fold with >20% tumor infiltration.
Measured: From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)
Part 1b: PFS in Participants With TP53 WT Neuroblastoma Assessed According to INRC
PFS was defined as the time from initiation of study drug to the first documented occurrence of PD or death from any cause (whichever occurs first), as determined by the investigator using INRC for participants with neuroblastoma. Primary tumor: PD= >20% increase in LD from smallest sum \& minimum 5 mm increase in LD. Soft tissue \& bone metastases: PD=new soft tissue lesions per CT/MRI or MIBG/FDG-PET avid bone site. Bone marrow: PD=new tumor infiltration >5% or infiltration increased >2-fold with >20% tumor infiltration.
Measured: From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)
Parts 1a and 1b: Overall Survival (OS) in SE Population
OS was defined as the time from initiation of the study drug to death from any cause. Estimates for median OS were computed using Kaplan-Meier methodology
Measured: Up to approximately 29 months
Part 1b: OS in Participants With TP53 WT Neuroblastoma
OS was defined as the time from initiation of the study drug to death from any cause. Estimates for median OS were computed using Kaplan-Meier methodology
Measured: Up to approximately 29 months
Part 1a: ORR Irrespective of TP53 Status in Participants With Solid Tumor From SE Population According to RECIST v1.1 or INRC
ORR was defined as the percentage of participants with CR or PR at any time during study treatment, on two consecutive occasions >= 4 weeks apart, as determined by the investigator according to RECIST v1.1 or INRC. Per RECIST, CR was defined as disappearance of all target lesions. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. Participants who had neuroblastoma were assessed by INRC. Per INRC, CR= <10 mm residual soft tissue at primary site and complete resolution of MIBG or FDG-PET uptake at primary site. PR= ≥ 30% decrease in longest diameter of primary site and MIBG or FDG-PET uptake at primary site stable, improved, or resolved. Soft tissue \& bone metastases: CR= resolution of all disease sites; PR= ≥30% decrease in sum of non-primary target lesions, with no new lesions or ≥50% reduction in MIBG score or in number of FDG-PET-avid bone lesions; Bone marrow: CR= no tumor infiltration on reassessment.
Measured: From screening (maximum 28 days) up to Cycle 5 (cycle length=28 days)
Part 1b: ORR Irrespective of TP53 Status in Participants With Neuroblastoma From SE Population According to INRC
ORR was defined as the percentage of participants with CR or PR at any time during study treatment, on 2 consecutive occasions ≥ 4 weeks apart, as determined by the investigator per INRC. Primary tumor: CR= <10 mm residual soft tissue at primary site and complete resolution of MIBG or FDG-PET uptake at primary site. PR= ≥ 30% decrease in longest diameter of primary site and MIBG or FDG-PET uptake at primary site stable, improved, or resolved. Soft tissue \& bone metastases: CR= resolution of all disease sites; PR= ≥30% decrease in sum of non-primary target lesions, with no new lesions or ≥50% reduction in MIBG score or in number of FDG-PET-avid bone lesions; Bone marrow: CR= no tumor infiltration on reassessment. Percentages have been rounded off to nearest decimal point.
Measured: From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)
Part 1a: Maximum Plasma Concentration (Cmax) of Idasanutlin as a Monotherapy
Measured: Days 1 and 5 of Cycle 1 (cycle length = 28 days)
Part 1b: Cmax of Idasanutlin in Combination With Chemotherapy or Venetoclax
Measured: Days 1 and 5 of Cycle 1 (cycle length = 28 days)
Part 1a: Cmax of Idasanutilin Metabolite M4 Following Idasanutilin as a Monotherapy
Measured: Days 1 and 5 of Cycle 1 (cycle length = 28 days)
Part 1b: Cmax of Idasanutlin Metabolite M4 (Idasanutilin in Combination With Chemotherapy or Venetoclax)
Measured: Days 1 and 5 of Cycle 1 (cycle length = 28 days)
Part 1b: Plasma Concentration of Venetoclax in Combination With Idasanutlin
Measured: Cycle 1: Predose on Days 2 and 5, 4 and 6 hours post dose on Days 1 and 5 (1 cycle = 28 days)
Parts 1, 2 and 3: Number of Participants With Leukemia Receiving Transplant After Study Treatment
Measured: Up to approximately 29 months
Parts 1, 2 and 3: Duration of Objective Response in Participants With Leukemia
DOR, defined as the time from the first tumor assessment that supports the participant's objective response (CR, CRp, CRi) to the time of relapse, or death from any cause, whichever occurs first. CR=Bone marrow blasts <5% (AML) and no evidence of circulating blasts, must be <1% (ALL); absence of blasts with Auer rods (AML); absence of extramedullary disease; absolute neutrophil count (ANC) >1.0*10^9/L [1000µL]; platelet count > 100*10^9/L (100,000/µL); independence of transfusions for a minimum of 1 week (AML and ALL). CRi= All CR criteria except for ANC <1.0*10^9/L[1000/µL] or insufficient recovery of platelet count <100* 10^9/L [100,000/µL] (AML and ALL). CRp=All CR criteria except for ANC >1.0*10^9/L[1000/µL]) or but with insufficient recovery of platelet (<100* 10^9/L [100,000/µL]) (ALL). Relapse=participants who achieved a CR/CRp/CRi \& subsequently developed: Bone marrow blasts ≥5%; reappearance of blasts in the blood ≥1%; or development of extra-medullary disease.
Measured: Up to approximately 29 months
Parts 1, 2 and 3: Event-Free Survival (EFS) in Participants With Leukemia
EFS=time from initiation of study drug to first documented occurrence of M3 marrow after Cycle 1, failure to achieve CR/CRp/CRi after Cycle 2, disease progression, relapse after achieving CR/CRp/CRi, or death from any cause, whichever occurs first. CR=Bone marrow blasts <5% (AML) \& no evidence of circulating blasts, must be <1% (ALL); absence of blasts with Auer rods (AML); absence of extramedullary disease; ANC >1.0*10^9/L [1000µL]; platelet count > 100*10^9/L (100,000/µL); no transfusions for a minimum of 1 week (AML \& ALL). CRi= All CR criteria except for ANC <1.0*10^9/L[1000/µL] or insufficient recovery of platelet count <100* 10^9/L [100,000/µL] (AML \& ALL). CRp=All CR criteria except for ANC >1.0*10^9/L[1000/µL]) or but with insufficient recovery of platelet (<100* 10^9/L [100,000/µL]) (ALL). Relapse=participants who achieved a CR/CRp/CRi \& subsequently developed: Bone marrow blasts ≥5%; reappearance of blasts in blood ≥1%; or development of extra-medullary disease.
Measured: Up to approximately 29 months
Parts 1, 2 and 3: OS in Participants With Leukemia
OS was defined as the time from initiation of study drug to death from any cause.
Measured: Up to approximately 29 months
Parts 1, 2 and 3: CRR of Efficacy-evaluable Population Irrespective of TP53 Status in Participants With Leukemia
CRR was defined as the percentage of participants with CR, CRi, or CRp within 2 cycles of study treatment. CR=Bone marrow blasts <5% (AML) and no evidence of circulating blasts, must be <1% (ALL); absence of blasts with Auer rods (AML); absence of extramedullary disease; absolute neutrophil count (ANC) >1.0*10^9/L [1000/µL]; platelet count > 100*10^9/L (100,000/µL); independence of transfusions for a minimum of 1 week (AML and ALL). CRi= All CR criteria except for ANC <1.0*10^9/L[1000/µL] or insufficient recovery of platelet count <100* 10^9/L [100,000/µL] (AML and ALL). CRp=All CR criteria except for ANC >1.0*10^9/L[1000/µL]) or but with insufficient recovery of platelet (<100* 10^9/L [100,000/µL]) (ALL).
Measured: Up to approximately 29 months
Parts 1, 2 and 3: MRD - Negative Rate in Participants With ALL
MRD - negative rate was defined as defined as the percentage of participants with AML who are MRD negative within 2 cycles of study treatment.
Measured: Up to approximately 29 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2019
- Study start27 Jan 2020
- Primary completion6 May 2024
- Study completion6 May 2024
Why it stopped: Study was terminated by the sponsor based on insufficient tolerability and efficacy to proceed beyond Part 1b.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid Leukemia (AML)Studies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04029688
- Sponsor's protocol ID
- GO40871
- Other IDs
- 2018-004579-11, 2018
- Status last verified
- Dec 2024
- First submitted
- 19 Jul 2019
- Last updated
- 20 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).
Publications
Rubio-San-Simon A, Marshall LV, Doz F, Mora J, Bielamowicz K, Corradini N, Langevin AM, Narendran A, Smith AA, Zwaan CM, Gho D, Cardenas A, Fowler S, Guizani C, Breton V, Wulff B, Bernardi R, Trippett T, Campbell-Hewson Q. Idasanutlin in Combination with Chemotherapy or Venetoclax in Pediatric and Young Adult Patients with Relapsed/Refractory Solid Tumors (iMATRIX Idasa): Results of a Phase I/II, Multicenter, Multi-arm Study. Target Oncol. 2026 Jan;21(1):87-102. doi: 10.1007/s11523-025-01186-w. Epub 2025 Dec 11.
PubMed 41379293
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II, Multicenter, Open-Label, Multi-Arm Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Preliminary Activity of Idasanutlin in Combination With Either Chemotherapy or Venetoclax in the Treatment of Pediatric and Young Adult Patients With Relapsed/Refractory Acute Leukemias or Solid Tumors
- ClinicalTrials.gov ID
- NCT04029688
- Acronym / sponsor ID
- GO40871
- Conditions
- Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), Neuroblastoma, Solid Tumors
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated by the sponsor based on insufficient tolerability and efficacy to proceed beyond Part 1b.
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 27 Jan 2020 (actual)
- Primary completion
- 6 May 2024 (actual)
- Study completion
- 6 May 2024 (actual)
- First posted
- 23 Jul 2019 (actual)
- Results
- Posted 20 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase I/II, multicenter, open-label, multi-arm study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of idasanutlin, administered as a single agent or in combination with chemotherapy or venetoclax, in pediatric and young adult participants with acute leukemias or solid tumors.
This study is divided into three parts: Part 1 will begin with dose escalation of idasanutlin as a single agent in pediatric participants with relapsed or refractory solid tumors to identify the maximum tolerated dose (MTD)/maximum administered dose (MAD) and to characterize dose-limiting toxicities (DLTs). Following MTD/MAD identification, three separate safety run-in cohorts in neuroblastoma, acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL) will be conducted to identify the recommended Phase 2 dose (RP2D) of idasanutlin in each combination, with chemotherapy or venetoclax. Part 2 will evaluate the safety and early efficacy of idasanutlin in combination with chemotherapy or venetoclax in newly enrolled pediatric and young adult participants in neuroblastoma, AML,and ALL cohorts at idasanutlin RP2D. Part 3 will potentially be conducted as an additional expansion phase of the idasanutlin combination cohorts in neuroblastoma, AML, or ALL for further response and safety assessment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation: Solid Tumors: Idasanutlin Single Agent | Experimental | Drug: Idasanutlin |
| Neuroblastoma: Idasanutlin + Venetoclax | Experimental | Drug: Idasanutlin, Drug: Venetoclax |
| Neuroblastoma: Idasanutlin + Cyclophosphamide + Topotecan | Experimental | Drug: Idasanutlin, Drug: Cyclophosphamide, Drug: Topotecan |
| AML: Idasanutlin + Venetoclax | Experimental | Drug: Idasanutlin, Drug: Venetoclax, Drug: Intrathecal Chemotherapy |
| AML: Idasanutlin + Fludarabine + Cytarabine | Experimental | Drug: Idasanutlin, Drug: Fludarabine, Drug: Cytarabine, Drug: Intrathecal Chemotherapy |
| ALL: Idasanutlin + Venetoclax | Experimental | Drug: Idasanutlin, Drug: Venetoclax, Drug: Intrathecal Chemotherapy |
Who may qualify
- Ages
- 0 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (14 listed)
- The participants ages are < 18 for part 1a, < 30 for Parts 1b. 2 and 3
- Study Part 1 (single-agent therapy dose escalation): histologically confirmed diagnosis of neuroblastoma or other solid tumor that has progressed or recurred despite standard therapy, and for which there is no therapy proven to prolong survival with an acceptable quality of life
- Study Part 1 (combination safety run-in), Study Part 2 (initial expansion), and Study Part 3 (additional expansion): histologically confirmed diagnosis of neuroblastoma, AML, or precursor-B ALL that has progressed or recurred despite, or is refractory to, standard therapy
- Adequate performance status: Participants <16 years of age: Lansky greater than or equal to (≥)50%; Patients ≥16 years of age: Karnofsky ≥50%
- Adequate end-organ function, as defined in the protocol
Key exclusion criteria (21 listed)
- Primary Central Nervous System (CNS) tumors
- Symptomatic CNS metastases that result in a neurologically unstable clinical state or require increasing doses of corticosteroids or local CNS-directed therapy to control the CNS disease
- CNS3 leukemia
- Acute promyelocytic leukemia
- White blood cell count >50 × 10^9 cells/Liter (L)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IdasanutlinAlso: RG7388Idasanutlin will be administered as an oral medication once daily on Days 1-5 of a 28-day cycle. | Drug | ALL: Idasanutlin + Venetoclax, AML: Idasanutlin + Fludarabine + Cytarabine, AML: Idasanutlin + Venetoclax, Dose Escalation: Solid Tumors: Idasanutlin Single Agent, Neuroblastoma: Idasanutlin + Cyclophosphamide + Topotecan, Neuroblastoma: Idasanutlin + Venetoclax |
| VenetoclaxAlso: RG7601, GDC-0199, ABT-199Venetoclax will be administered orally at the adult dose equivalent (adjusted by body weight) of 400 milligrams (mg) in participants with neuroblastoma and the adult dose equivalent of 600 mg in participants with leukemia. | Drug | ALL: Idasanutlin + Venetoclax, AML: Idasanutlin + Venetoclax, Neuroblastoma: Idasanutlin + Venetoclax |
| CyclophosphamideCyclophosphamide will be administered once daily on Days 1-5 of each 28-day cycle at 250 milligrams per meter squared of body surface area (mg/m^2) as an intravenous (IV) infusion. | Drug | Neuroblastoma: Idasanutlin + Cyclophosphamide + Topotecan |
| TopotecanTopotecan will be administered once daily on Days 1-5 of each 28-day cycle at 0.75 mg/m^2 as an IV infusion. | Drug | Neuroblastoma: Idasanutlin + Cyclophosphamide + Topotecan |
| FludarabineFludarabine will be administered once daily on Days 1-5 of each 28-day treatment cycle at 30 mg/m^2 as an IV infusion. | Drug | AML: Idasanutlin + Fludarabine + Cytarabine |
| CytarabineCytarabine will be administered once daily on Days 1-5 of each 28-day treatment cycle at 2000 mg/m^2 as an IV infusion. | Drug | AML: Idasanutlin + Fludarabine + Cytarabine |
| Intrathecal ChemotherapyAll participants with leukemia, irrespective of arm, will receive intrathecal chemotherapy on Day 1 of each 28-day treatment cycle. Intrathecal chemotherapy will consist of either single-agent cytarabine or methotrexate, or a combination of methotrexate, cytarabine, and hydrocortisone, at appropriate age-based dosing as specified in the protocol. | Drug | ALL: Idasanutlin + Venetoclax, AML: Idasanutlin + Fludarabine + Cytarabine, AML: Idasanutlin + Venetoclax |
Primary outcome
Part 1a and 1b: Number of Participants With Adverse Events (AEs) and Severity of AEs Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5 (NCI CTCAE v5.0)
Time frame: From screening up to 30 days after study treatment discontinuation (approximately 7 months)
An AE is any untoward medical occurrence in participant administered a pharmaceutical product \& regardless of causal relationship with this treatment. An AE can therefore be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product. AEs were graded as per NCI CTCAE v5.0. Grade 1=Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated; Grade 2=Moderate; minimal, local or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living; Grade 3=Severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living; Grade 4=Life-threatening consequences/urgent intervention indicated; Grade 5=Death related to adverse event.
Parts 1a and 1b: Number of Participants With Dose-Limiting Toxicities (DLTs)
Time frame: Cycle 1 (one cycle is 28 days)
DLTs were assessed for single-agent idasanutlin and idasanutlin in combination with chemotherapy or venetoclax. A DLT was defined as any AE that occurred during the DLT assessment window and was assessed by the investigator as related or possibly related to idasanutlin. An AE is an untoward medical occurrence in participant administered a pharmaceutical product \& regardless of causal relationship with this treatment. Following events were considered to be DLTs: any treatment-related death; elevation of serum hepatic transaminase; severe liver injury, in the absence of cholestasis or other causes of hyperbilirubinemia; any non-hematologic toxicity Grade ≥3; nausea, vomiting, and/or diarrhea if Grade 3 severity lasts > than 24 hours after initiation of supportive care measures or if Grade 4 or higher; hematologic toxicity; any related event that results in a dose delay beyond Day 42.
Part 1b: Objective Response Rate (ORR) in Participants With TP53 Wild-Type (WT) Neuroblastoma Assessed According to International Neuroblastoma Response Criteria (INRC)
Time frame: From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)
ORR was defined as the percentage of participants with complete response (CR) or partial response (PR) at any time during study treatment, on 2 consecutive occasions ≥ 4 weeks apart, as determined by the investigator per INRC. Primary tumor: CR = <10 millimeters (mm) residual soft tissue at primary site and complete resolution of meta-iodobenzylguanidine (MIBG) or fluorodeoxyglucose-positron emission tomography (FDG-PET) uptake at primary site. PR = ≥ 30% decrease in longest diameter of primary site and MIBG or FDG-PET uptake at primary site stable, improved, or resolved. Soft tissue \& bone metastases: CR = resolution of all disease sites; PR = ≥30% decrease in sum of non-primary target lesions, with no new lesions or ≥50% reduction in MIBG score or in number of FDG-PET-avid bone lesions; Bone marrow: CR = no tumor infiltration on reassessment.
Parts 2 and 3: ORR in Participants With TP53 WT Neuroblastoma Assessed According to INRC
Time frame: Up to approximately 29 months
ORR was defined as the percentage of participants with CR or PR at any time during study treatment, on 2 consecutive occasions ≥ 4 weeks apart, as determined by the investigator per INRC. Primary tumor: CR = <10 mm residual soft tissue at primary site and complete resolution of MIBG or FDG-PET uptake at primary site. PR = ≥ 30% decrease in longest diameter of primary site and MIBG or FDG-PET uptake at primary site stable, improved, or resolved. Soft tissue \& bone metastases: CR = resolution of all disease sites; PR = ≥30% decrease in sum of non-primary target lesions, with no new lesions or ≥50% reduction in MIBG score or in number of FDG-PET-avid bone lesions; Bone marrow: CR = no tumor infiltration on reassessment.
Parts 2 and 3: Complete Remission Rate (CRR) in Participants With TP53 WT Leukemia
Time frame: Up to Cycle 2 (cycle length=28 days) (approximately 8 weeks)
CRR was defined as the percentage of participants with morphologic complete remission (CR), complete remission with incomplete blood count recovery (CRi), or complete remission with incomplete platelet count recovery (CRp) within 2 cycles of study treatment. CR=Bone marrow blasts <5% (AML) and no evidence of circulating blasts, must be <1% (ALL); absence of blasts with Auer rods (AML); absence of extramedullary disease; absolute neutrophil count (ANC) >1.0*10^9/liter (L) [1000/microliter (µL)]; platelet count > 100*10^9/L (100,000/µL); independence of transfusions for a minimum of 1 week (AML and ALL). CRi= All CR criteria except for ANC <1.0*10^9/L[1000/µL] or insufficient recovery of platelet count <100* 10^9/L [100,000/µL] (AML and ALL). CRp=All CR criteria except for ANC >1.0*10^9/L[1000/µL]) or but with insufficient recovery of platelet (<100* 10^9/L [100,000/µL]) (ALL).
Parts 2 and 3: Minimal Residual Disease (MRD) - Negative Rate in Participants With ALL
Time frame: Up to Cycle 2 (cycle length=28 days) (approximately 8 weeks)
MRD - negative rate was defined as percentage of participants with ALL who have an MRD value < 0.01%, as measured by next-generation sequencing (NGS), within 2 cycles of study treatment.
24 secondary outcomes
Part 1a: Clinical Benefit Rate (CBR) in Participants With Solid Tumors From SE Population Assessed According to Response Evaluation Criteria Version 1.1 (RECIST v1.1) or INRC
Time frame: From screening (maximum 28 days) up to Cycle 5 (cycle length=28 days)
Part 1b: CBR in Participants With Neuroblastoma From SE Population Assessed According to INRC
Time frame: From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)
Part 1b: CBR in Participants With TP53 WT Neuroblastoma Assessed According to INRC
Time frame: From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)
Part 1a: Duration of Response (DOR) in Participants With Solid Tumors From SE Population Assessed According to RECIST v1.1 or INRC
Time frame: From screening (maximum 28 days) up to Cycle 5 (cycle length=28 days)
Part 1b: DOR in Participants With Neuroblastoma From SE Population Assessed According to INRC
Time frame: From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)
Part 1b: DOR in in Participants With TP53 WT Neuroblastoma Assessed According to INRC
Time frame: From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)
Part 1a: Progression Free Survival (PFS) in Participants With Solid Tumors From SE Population Assessed According to RECIST v1.1 or INRC
Time frame: From screening (maximum 28 days) up to Cycle 5 (cycle length=28 days)
Part 1b: PFS in Participants With Neuroblastoma From SE Population Assessed According to INRC
Time frame: From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)
Part 1b: PFS in Participants With TP53 WT Neuroblastoma Assessed According to INRC
Time frame: From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)
Parts 1a and 1b: Overall Survival (OS) in SE Population
Time frame: Up to approximately 29 months
Part 1b: OS in Participants With TP53 WT Neuroblastoma
Time frame: Up to approximately 29 months
Part 1a: ORR Irrespective of TP53 Status in Participants With Solid Tumor From SE Population According to RECIST v1.1 or INRC
Time frame: From screening (maximum 28 days) up to Cycle 5 (cycle length=28 days)
Part 1b: ORR Irrespective of TP53 Status in Participants With Neuroblastoma From SE Population According to INRC
Time frame: From screening (maximum 28 days) up to Cycle 6 (cycle length=28 days)
Part 1a: Maximum Plasma Concentration (Cmax) of Idasanutlin as a Monotherapy
Time frame: Days 1 and 5 of Cycle 1 (cycle length = 28 days)
Part 1b: Cmax of Idasanutlin in Combination With Chemotherapy or Venetoclax
Time frame: Days 1 and 5 of Cycle 1 (cycle length = 28 days)
Part 1a: Cmax of Idasanutilin Metabolite M4 Following Idasanutilin as a Monotherapy
Time frame: Days 1 and 5 of Cycle 1 (cycle length = 28 days)
Part 1b: Cmax of Idasanutlin Metabolite M4 (Idasanutilin in Combination With Chemotherapy or Venetoclax)
Time frame: Days 1 and 5 of Cycle 1 (cycle length = 28 days)
Part 1b: Plasma Concentration of Venetoclax in Combination With Idasanutlin
Time frame: Cycle 1: Predose on Days 2 and 5, 4 and 6 hours post dose on Days 1 and 5 (1 cycle = 28 days)
Parts 1, 2 and 3: Number of Participants With Leukemia Receiving Transplant After Study Treatment
Time frame: Up to approximately 29 months
Parts 1, 2 and 3: Duration of Objective Response in Participants With Leukemia
Time frame: Up to approximately 29 months
Parts 1, 2 and 3: Event-Free Survival (EFS) in Participants With Leukemia
Time frame: Up to approximately 29 months
Parts 1, 2 and 3: OS in Participants With Leukemia
Time frame: Up to approximately 29 months
Parts 1, 2 and 3: CRR of Efficacy-evaluable Population Irrespective of TP53 Status in Participants With Leukemia
Time frame: Up to approximately 29 months
Parts 1, 2 and 3: MRD - Negative Rate in Participants With ALL
Time frame: Up to approximately 29 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41379293Rubio-San-Simon A, Marshall LV, Doz F, Mora J, Bielamowicz K, Corradini N, Langevin AM, Narendran A, Smith AA, Zwaan CM, Gho D, Cardenas A, Fowler S, Guizani C, Breton V, Wulff B, Bernardi R, Trippett T, Campbell-Hewson Q. Idasanutlin in Combination with Chemotherapy or Venetoclax in Pediatric and Young Adult Patients with Relapsed/Refractory Solid Tumors (iMATRIX Idasa): Results of a Phase I/II, Multicenter, Multi-arm Study. Target Oncol. 2026 Jan;21(1):87-102. doi: 10.1007/s11523-025-01186-w. Epub 2025 Dec 11.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
14 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Idasanutlin, Venetoclax and Cyclophosphamide in people with Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL), run by Hoffmann-La Roche at 14 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States, United Kingdom, France, Spain, Canada and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1a and 1b: Number of Participants With Adverse Events (AEs) and Severity of AEs Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5 (NCI CTCAE v5.0) (time frame: From screening up to 30 days after study treatment discontinuation (approximately 7 months)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04029688, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2024.