Acute Myeloid LeukemiaPhase 1NCT05330377
GM-CLAG in Relapsed/Refractory FLT3-mutated AML
A Phase 1 study testing Gilteritinib 40 MG Oral Tablet, Cladribine and Cytarabine in people with Acute Myeloid Leukemia, run by Ayman H Qasrawi at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the dose-limiting toxicities (DLT) and define the maximum tolerated dose (MTD) and the recommended phase II study dose of gilteritinib when combined with mitoxantrone, cladribine, cytarabine and filgrastim (GM-CLAG) in participants with FLT3- mutated relapsed or refractory… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Gilteritinib 40 MG Oral Tablet, Cladribine and Cytarabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2023to 30 May 2032
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed, morphologically documented AML in first or subsequent relapse or primary induction failure. The diagnosis should be documented within 28 days prior to enrollment.
- Relapsed AML is defined as the reappearance of leukemic blasts in the bone marrow, peripheral blood, or any extramedullary site after the attainment of a CR/CRi, detected by morphology, flow cytometry, or immunohistochemistry.
- Primary induction failure is defined as failure to achieve a CR or CRi after two courses of induction chemotherapy given per physician's choice or institution's guidelines.
- Patients with previous allogeneic hematopoietic stem cell transplantation are allowed to participate, as are prior autologous HCT.
- Evidence of FLT3-ITD or FLT3-TKD mutations as detected by polymerase chain reaction and/or next-generation sequencing by peripheral blood and/or bone marrow samples obtained at the time of relapse. FLT3 positivity should be documented before enrollment.
- Allowable prior therapies include: First-line AML therapy including cytarabine, anthracyclines, gemtuzumab ozogamicin, prior hypoemethylating agents with or without venetoclax and/or FLT3 inhibitors.
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- Prior clinical trial participation is allowed with a washout period of experimental drug of at least 4 weeks.
- Prior treatment with the FLT3 inhibitor gilteritinib is allowed (must be 12 months or greater from time of eligibility screening).
- Age ≥18 years.
- ECOG performance status of 0 or 1; Karnofsky 70% or higher (APPENDIX A).
- Probability of treatment-related mortality (TRM) <13.1% as calculated by performance status, age, platelet count, albumin, secondary vs primary AML, WBC count, creatinine, and percentage of peripheral blood blasts.50
- This score corresponds to corresponding to a ≤13.1% probability of 4-week mortality. Although this score was validated for newly diagnosed AML, it was previously used in the relapsed/refractory setting.30,51,52 (see APPENDIX B). An online calculator is available at: https://cstaging.fhcrc-research.org/TRM/).
- Adequate organ function as defined below:
- Creatinine clearance (CrCl) >60 mL/min as measured by Cockcroft-Gault formula (APPENDIX C).
- Ejection fraction (EF) ≥ 50% as documented by an echocardiogram or multiple gated cardiac blood pool imaging (MUGA) if the echocardiogram's result is judged to be unreliable by the performing cardiologist.
- Total bilirubin ≤ 1.5 × the ULN, unless due to Gilbert's, hemolysis or leukemic infiltration, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN, unless caused by leukemic infiltration.
- Female participants must be either:
- Of non-child bearing potential i. postmenopausal status prior to eligibility screening (defined as at least 12 consecutive months of amenorrhea), or ii. undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy).
- Of childbearing potential. These women must agree to all of the following: i. Negative serum/urine pregnancy test at eligibility screening. ii. Abstain from pregnancy during the study and for 6 months after the final study drug administration.
- If heterosexually active, agree to consistently use highly effective contraception per locally accepted standards in addition to a barrier method starting at eligibility screening and throughout the study period and for 6 months after the final study drug administration.
- Female participants must agree not to breastfeed or donate ova throughout the study drug treatment period and for 6 months after the final study drug administration.
- Male patients should agree to:
- Avoid impregnating a female partner, during the study and for 180 days after the final study drug administration.
- Avoid donating sperm during the study and for 180 days after the final study drug administration.
- Consistently use highly effective contraception in addition to a barrier method (even if surgically sterilized) along with their partners who are women of childbearing potential, throughout the study drug treatment period and for 6 months after the final study drug administration.
- Ability to understand and willingness to sign a written informed consent document.
Who cannot join
- History of prior treatment with gilteritinib within the last 12 months.
- Purine analogue (cladribine and fludarabine) treatment as part of their last line of therapy.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to gilteritinib or other agents used in this study (CLAG-M).
- Diagnosis of acute promyelocytic leukemia, BCR/ABL1-positive AML or chronic myelogenous leukemia in blast crisis.
- Inability to swallow oral medications or gastrointestinal disease limiting absorption of oral agents.
- Patients with a history of allo-SCT should not have active or acute chronic GVHD requiring systemic immunosuppression; topical GVHD treatment is allowed.
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- Participant has an uncontrolled infection. If a bacterial or viral infection is present, the participant must be receiving definitive therapy and has no signs of progressing infection for 72 hours prior to registration. If a fungal infection is present, the participant must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection for 1 week prior to registration.
- Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection.
- Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
- Active hepatitis B virus (HBV) infection as evidenced by positive hepatitis B surface antigen and/or Nucleic Acid Amplification Testing (NAAT). Patients with prior history of cleared HBV infection (negative hepatitis B surface antigen, positive hepatitis B surface antibody, and positive hepatitis B core IgG antibody) could be allowed to participate after consultation with a hepatologist, in which case Hep B viral load will be monitored by qPCR per institutional guidelines. In this case, concomitant suppressive antiviral therapy against HBV might be warranted.
- Uncontrolled HIV infection. Patients who have controlled infection on antiretroviral therapy are allowed, defined as HIV RNA below level of detection for the institution's standard assay.
- History of heart failure, myocarditis, or cardiomyopathy which requires heart failure directed therapy.
- Participant has long QT Syndrome at screening.
- Participant has a Fridericia-corrected QT interval (QTcF) > 450 msec (average of triplicate determinations). Prolonged QTc interval associated with bundle branch block or pacemaking is permitted with written approval of the Principal Investigator (PI).
- Untreated CNS leukemia. Evaluation of cerebrospinal fluid (CSF) or brain MRI during screening is only required if there is a clinical suspicion of CNS involvement by leukemia during screening. Patients who previously had CNS leukemia that resolved with therapy should undergo CSF sampling +/- brain MRI within 2 weeks prior to enrollment to exclude CNS relapse.
- History of auto-immune conditions requiring active immunosuppressive therapy.
- Patients with uncontrolled intercurrent illness including, but not limited to, symptomatic decompensated congestive heart failure; unstable angina pectoris; cardiac arrhythmia or any acute pulmonary condition requiring need for supplemental oxygen.
- Participant is receiving concomitant drugs that are strong inducers of CYP3A except for drugs considered essential for the care of the patient.
- Any medical condition which, in the investigator's opinion, could compromise the patient's safety.
- Patients with psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant or lactating women.
- Participants who are receiving any other investigational treatment agents.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase Ib Trial of Gilteritinib in Combination With Mitoxantrone, Cladribine, Cytarabine and Filgrastim (GM-CLAG) for Relapsed/Refractory FLT3-mutated Acute Myeloid Leukemia
The purpose of this study is to evaluate the dose-limiting toxicities (DLT) and define the maximum tolerated dose (MTD) and the recommended phase II study dose of gilteritinib when combined with mitoxantrone, cladribine, cytarabine and filgrastim (GM-CLAG) in participants with FLT3- mutated relapsed or refractory (R/R) acute myeloid leukemia (AML).
Read the detailed description
The treatment of FLT3- mutated relapsed or refractory (R/R) is challenging. Gilteritinib, as a single agent, is the first FLT3 inhibitor to be FDA approved in the R/R setting. This phase I clinical trial will evaluate DLT/MTD and the recommended phase II study dose of gilteritinib when combined with mitoxantrone, cladribine, cytarabine and filgrastim (CLAG-M) in patients with FLT3- mutated R/R AML. This study will also evaluate the pharmacodynamics and pharmacokinetics of gilteritinib when combined with CLAG-M at specific time points. Although this combination has not been established to have superior clinical benefit in comparison to single-agent gilteritinib, the objective of this trial is to provide a possible therapeutic benefit in addition to safety and tolerability.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Gilteritinib 40 MG Oral Tablet, Cladribine, Cytarabine, Filgrastim, Mitoxantrone
- Keywords
- FLT3, CLAG-M, AML, Relapsed, Refractory, Gilteritinib
- Medical subject headings
- Leukemia, Myeloid, Acute, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gilteritinib 40 MG Oral TabletDrug
Also called Xospata
Gilteritinib is an oral FLT3 inhibitor, and is active against both FLT3-ITD and FLT3-TKD mutations. Gilteritinib will be given orally according to the assigned phase I dose cohort starting day 6 until day 19. Participants will be given the daily dose with water as at the same time each morning. Gilteritinib should be taken at least 2 hours after or 1 hour before consuming food.
CladribineDrug
Also called Leustatin
Cladribine is given intravenously at a dose of 5 mg/m2 I.V. over 2 hours once per day on days 1 to 5.
CytarabineDrug
Also called cytosine arabinoside (Ara-C)
Cytarabine is given intravenously at a dose of 2,000 mg/m2 I.V. over 4 hours once per day on days 1 to 5, given second, 2 hours after cladribine.
FilgrastimDrug
Also called GCSF, Filgrastim sndz
Filgrastim (GCSF) or biosimilar, will be given at a dose of 300 mcg S.C. once per day on days 0 to 5, started 24 hours prior to chemotherapy. If WBC is > 20 × 109/L on day 0, the filgrastim dose on day 0 will be omitted.
MitoxantroneDrug
Also called Novantrone
Mitoxantrone is given intravenously at a dose of 10 mg/m2 I.V. over 2 hours once per day on days 1 to 3.
| Study group | Role | What they receive |
|---|---|---|
| Gilteritinib (Dose Level -1: 40 mg/day) | Experimental | Dose escalation for gilteritinib will be conducted according to a BOIN design. Gilteritinib 40 mg/day will be given orally starting day 6 until day 19. CLAG-M chemotherapy will be administered at a fixed dose and schedule as following:
* Cladribine (CL) 5 mg/m2 I.V. over 2 hours once per day on days 1 to 5, given first.
* Cytarabine (A) 2,000 mg/m2 I.V. over 4 hours once per day on days 1 to 5, given second, 2 hours after cladribine.
* Filgrastim (GCSF) 300 mcg S.C. once per day on days 0 to 5, started 24 hours prior to chemotherapy. If WBC is > 20 × 109/L on day 0, the filgrastim dose on day 0 will be omitted.
* Mitoxantrone (M) 10 mg/m2 I.V. once per day on days 1 to 3 Receives: Drug: Gilteritinib 40 MG Oral Tablet; Drug: Cladribine; Drug: Cytarabine; Drug: Filgrastim; Drug: Mitoxantrone |
| Gilteritinib (Dose Level 1: 80 mg/day) | Experimental | Dose escalation for gilteritinib will be conducted according to a BOIN design. Gilteritinib 80 mg/day will be given orally starting day 6 until day 19. CLAG-M chemotherapy will be administered at a fixed dose and schedule as following:
* Cladribine (CL) 5 mg/m2 I.V. over 2 hours once per day on days 1 to 5, given first.
* Cytarabine (A) 2,000 mg/m2 I.V. over 4 hours once per day on days 1 to 5, given second, 2 hours after cladribine.
* Filgrastim (GCSF) 300 mcg S.C. once per day on days 0 to 5, started 24 hours prior to chemotherapy. If WBC is > 20 × 109/L on day 0, the filgrastim dose on day 0 will be omitted.
* Mitoxantrone (M) 10 mg/m2 I.V. once per day on days 1 to 3 Receives: Drug: Gilteritinib 40 MG Oral Tablet; Drug: Cladribine; Drug: Cytarabine; Drug: Filgrastim; Drug: Mitoxantrone |
| Gilteritinib (Dose Level 2: 120 mg/day) | Experimental | Dose escalation for gilteritinib will be conducted according to a BOIN design. Gilteritinib 120 mg/day will be given orally starting day 6 until day 19. CLAG-M chemotherapy will be administered at a fixed dose and schedule as following:
* Cladribine (CL) 5 mg/m2 I.V. over 2 hours once per day on days 1 to 5, given first.
* Cytarabine (A) 2,000 mg/m2 I.V. over 4 hours once per day on days 1 to 5, given second, 2 hours after cladribine.
* Filgrastim (GCSF) 300 mcg S.C. once per day on days 0 to 5, started 24 hours prior to chemotherapy. If WBC is > 20 × 109/L on day 0, the filgrastim dose on day 0 will be omitted.
* Mitoxantrone (M) 10 mg/m2 I.V. once per day on days 1 to 3 Receives: Drug: Gilteritinib 40 MG Oral Tablet; Drug: Cladribine; Drug: Cytarabine; Drug: Filgrastim; Drug: Mitoxantrone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicities (DLT) of gilteritinib when combined with mitoxantrone, cladribine, cytarabine and filgrastim (GM-CLAG)
DLT is defined as:
- Any treatment-related death
- Grade 4 neutropenia or thrombocytopenia lasting > 42 days from start of cycle in the absence of active AML
- Any Grade 4 or greater ANC lasting past cycle day 42
- Any Grade 4 or greater platelets lasting past cycle day 42
- Grade ≥ 4 organ toxicity (i.e., adverse reactions involving neurologic, pulmonary, cardiac, gastrointestinal, genitourinary, renal, hepatic, or cutaneous systems.)
- Confirmed Hy's law cases
Measured: 42 days
Maximally Tolerated Dose (MTD) of gilteritinib when combined with mitoxantrone, cladribine, cytarabine and filgrastim (GM-CLAG)
The MTD will be defined as the highest dose of Gilteritinib estimated to have less than 20% hematologic or non-hematologic DLT rates. Enrollment of next patient will be allowed only after prior cohort has completed Cycle 1 and recovered or failure of response has been documented by Day 42.
Measured: 42 days
Secondary outcomes (9)
Complete remission (CR) rate after completing induction chemotherapy with the GM-CLAG combination.
All the following criteria should be met:
- bone marrow blasts <5%
- absence of circulating blasts and blasts with Auer roda
- absence of extramedullary disease
- ANC ≥ 1.0 × 109 /L (1000/µL)
- platelet count ≥ 100 × 109 /L (100,000/µL).
Measured: 42 days
Complete remission with incomplete hematologic recovery (CRi) after completing induction chemotherapy with the GM-CLAG combination.
All CR criteria should be met except for residual neutropenia ANC ≤ 1.0 × 109 /L (1000/µL) or thrombocytopenia ≤ 100 × 109 /L (100,000 /µL).
Measured: 42 days
Complete remission with partial hematologic recovery (CRh) after completing induction chemotherapy with the GM-CLAG combination.
All CR criteria should be met except for residual neutropenia and thrombocytopenia with at least partial recovery as evidenced by: ANC ≥ 0.5 × 109 /L (500/µL) and platelet count ≥ 50 × 109 /L (100,000/µL).
Measured: 42 days
Composite complete remission (CRc) after completing induction chemotherapy with the GM-CLAG combination.
This is a composite rate of subjects who achieve a CR and those who achieve CRi.
Measured: 42 days
Minimal residual disease status (MRD) after completing induction chemotherapy with the GM-CLAG combination.
All hematologic criteria of CR; decrease of bone marrow blast percentage to 5% to 25%; MRD status will be determined by FLT3 polymerase chain reaction (PCR) testing of bone marrow aspirates obtained at the end of each cycle of induction.
Measured: Two Induction Cycles (each up to 42 days)
Best response to Induction Therapy
Best response is defined as the best measured response (CR, CRp, CRi, or PR) post-treatment.
Two best responses, up to the time of 2 cycles of treatment period will be defined.
Measured: Two Induction Cycles (each up to 42 days)
Percentage of patients proceeding to transplantation
To evaluate percentage of patients proceeding to transplantation at anytime during study period
Measured: Up to 2 years
Overall survival (OS)
Defined for all patients of the trial; measured from the date of registration to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive.
Measured: Up to 2 years
Leukemia-free survival (LFS)
Defined only for patients achieving CR, or CRi; measured from the date of achievement of a remission until the date of relapse or death from any cause.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2022
- Study startMar 2023 (estimated)
- Primary completion30 May 2027 (estimated)
- Study completion30 May 2032 (estimated)
Why it stopped: Sponsor withdrew funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ayman H Qasrawi
- Sponsor type
- University, hospital or other
- Collaborators
- Astellas Pharma Inc
- Responsible party
- Sponsor-investigator, Ayman H Qasrawi, University of Kentucky
- Investigators
- Ayman Qasrawi, MD, Principal investigator, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05330377
- Sponsor's protocol ID
- MCC-21-LEUK-18-PMC
- Status last verified
- Apr 2023
- First submitted
- 8 Apr 2022
- Last updated
- 25 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib Trial of Gilteritinib in Combination With Mitoxantrone, Cladribine, Cytarabine and Filgrastim (GM-CLAG) for Relapsed/Refractory FLT3-mutated Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT05330377
- Acronym / sponsor ID
- MCC-21-LEUK-18-PMC
- Conditions
- Acute Myeloid Leukemia
- Keywords
- FLT3, CLAG-M, AML, Relapsed, Refractory, Gilteritinib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Sponsor withdrew funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Ayman H QasrawiUniversity, hospital or other
- Collaborators
- Astellas Pharma Inc
- Study start
- Mar 2023 (estimated)
- Primary completion
- 30 May 2027 (estimated)
- Study completion
- 30 May 2032 (estimated)
- First posted
- 15 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the dose-limiting toxicities (DLT) and define the maximum tolerated dose (MTD) and the recommended phase II study dose of gilteritinib when combined with mitoxantrone, cladribine, cytarabine and filgrastim (GM-CLAG) in participants with FLT3- mutated relapsed or refractory (R/R) acute myeloid leukemia (AML).
Detailed description
The treatment of FLT3- mutated relapsed or refractory (R/R) is challenging. Gilteritinib, as a single agent, is the first FLT3 inhibitor to be FDA approved in the R/R setting. This phase I clinical trial will evaluate DLT/MTD and the recommended phase II study dose of gilteritinib when combined with mitoxantrone, cladribine, cytarabine and filgrastim (CLAG-M) in patients with FLT3- mutated R/R AML. This study will also evaluate the pharmacodynamics and pharmacokinetics of gilteritinib when combined with CLAG-M at specific time points. Although this combination has not been established to have superior clinical benefit in comparison to single-agent gilteritinib, the objective of this trial is to provide a possible therapeutic benefit in addition to safety and tolerability.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Gilteritinib (Dose Level -1: 40 mg/day) | Experimental | Drug: Gilteritinib 40 MG Oral Tablet, Drug: Cladribine, Drug: Cytarabine, Drug: Filgrastim, Drug: MitoxantroneDose escalation for gilteritinib will be conducted according to a BOIN design. Gilteritinib 40 mg/day will be given orally starting day 6 until day 19. CLAG-M chemotherapy will be administered at a fixed dose and schedule as following: * Cladribine (CL) 5 mg/m2 I.V. over 2 hours once per day on days 1 to 5, given first. * Cytarabine (A) 2,000 mg/m2 I.V. over 4 hours once per day on days 1 to 5, given second, 2 hours after cladribine. * Filgrastim (GCSF) 300 mcg S.C. once per day on days 0 to 5, started 24 hours prior to chemotherapy. If WBC is > 20 × 109/L on day 0, the filgrastim dose on day 0 will be omitted. * Mitoxantrone (M) 10 mg/m2 I.V. once per day on days 1 to 3 |
| Gilteritinib (Dose Level 1: 80 mg/day) | Experimental | Drug: Gilteritinib 40 MG Oral Tablet, Drug: Cladribine, Drug: Cytarabine, Drug: Filgrastim, Drug: MitoxantroneDose escalation for gilteritinib will be conducted according to a BOIN design. Gilteritinib 80 mg/day will be given orally starting day 6 until day 19. CLAG-M chemotherapy will be administered at a fixed dose and schedule as following: * Cladribine (CL) 5 mg/m2 I.V. over 2 hours once per day on days 1 to 5, given first. * Cytarabine (A) 2,000 mg/m2 I.V. over 4 hours once per day on days 1 to 5, given second, 2 hours after cladribine. * Filgrastim (GCSF) 300 mcg S.C. once per day on days 0 to 5, started 24 hours prior to chemotherapy. If WBC is > 20 × 109/L on day 0, the filgrastim dose on day 0 will be omitted. * Mitoxantrone (M) 10 mg/m2 I.V. once per day on days 1 to 3 |
| Gilteritinib (Dose Level 2: 120 mg/day) | Experimental | Drug: Gilteritinib 40 MG Oral Tablet, Drug: Cladribine, Drug: Cytarabine, Drug: Filgrastim, Drug: MitoxantroneDose escalation for gilteritinib will be conducted according to a BOIN design. Gilteritinib 120 mg/day will be given orally starting day 6 until day 19. CLAG-M chemotherapy will be administered at a fixed dose and schedule as following: * Cladribine (CL) 5 mg/m2 I.V. over 2 hours once per day on days 1 to 5, given first. * Cytarabine (A) 2,000 mg/m2 I.V. over 4 hours once per day on days 1 to 5, given second, 2 hours after cladribine. * Filgrastim (GCSF) 300 mcg S.C. once per day on days 0 to 5, started 24 hours prior to chemotherapy. If WBC is > 20 × 109/L on day 0, the filgrastim dose on day 0 will be omitted. * Mitoxantrone (M) 10 mg/m2 I.V. once per day on days 1 to 3 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Confirmed, morphologically documented AML in first or subsequent relapse or primary induction failure. The diagnosis should be documented within 28 days prior to enrollment.
- Evidence of FLT3-ITD or FLT3-TKD mutations as detected by polymerase chain reaction and/or next-generation sequencing by peripheral blood and/or bone marrow samples obtained at the time of relapse. FLT3 positivity should be documented before enrollment.
- Allowable prior therapies include: First-line AML therapy including cytarabine, anthracyclines, gemtuzumab ozogamicin, prior hypoemethylating agents with or without venetoclax and/or FLT3 inhibitors.
- Prior clinical trial participation is allowed with a washout period of experimental drug of at least 4 weeks.
- Prior treatment with the FLT3 inhibitor gilteritinib is allowed (must be 12 months or greater from time of eligibility screening).
Key exclusion criteria (22 listed)
- History of prior treatment with gilteritinib within the last 12 months.
- Purine analogue (cladribine and fludarabine) treatment as part of their last line of therapy.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to gilteritinib or other agents used in this study (CLAG-M).
- Diagnosis of acute promyelocytic leukemia, BCR/ABL1-positive AML or chronic myelogenous leukemia in blast crisis.
- Inability to swallow oral medications or gastrointestinal disease limiting absorption of oral agents.
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 |
|---|---|---|
| Gilteritinib 40 MG Oral TabletAlso: XospataGilteritinib is an oral FLT3 inhibitor, and is active against both FLT3-ITD and FLT3-TKD mutations. Gilteritinib will be given orally according to the assigned phase I dose cohort starting day 6 until day 19. Participants will be given the daily dose with water as at the same time each morning. Gilteritinib should be taken at least 2 hours after or 1 hour before consuming food. | Drug | Gilteritinib (Dose Level -1: 40 mg/day), Gilteritinib (Dose Level 1: 80 mg/day), Gilteritinib (Dose Level 2: 120 mg/day) |
| CladribineAlso: LeustatinCladribine is given intravenously at a dose of 5 mg/m2 I.V. over 2 hours once per day on days 1 to 5. | Drug | Gilteritinib (Dose Level -1: 40 mg/day), Gilteritinib (Dose Level 1: 80 mg/day), Gilteritinib (Dose Level 2: 120 mg/day) |
| CytarabineAlso: cytosine arabinoside (Ara-C)Cytarabine is given intravenously at a dose of 2,000 mg/m2 I.V. over 4 hours once per day on days 1 to 5, given second, 2 hours after cladribine. | Drug | Gilteritinib (Dose Level -1: 40 mg/day), Gilteritinib (Dose Level 1: 80 mg/day), Gilteritinib (Dose Level 2: 120 mg/day) |
| FilgrastimAlso: GCSF, Filgrastim sndzFilgrastim (GCSF) or biosimilar, will be given at a dose of 300 mcg S.C. once per day on days 0 to 5, started 24 hours prior to chemotherapy. If WBC is > 20 × 109/L on day 0, the filgrastim dose on day 0 will be omitted. | Drug | Gilteritinib (Dose Level -1: 40 mg/day), Gilteritinib (Dose Level 1: 80 mg/day), Gilteritinib (Dose Level 2: 120 mg/day) |
| MitoxantroneAlso: NovantroneMitoxantrone is given intravenously at a dose of 10 mg/m2 I.V. over 2 hours once per day on days 1 to 3. | Drug | Gilteritinib (Dose Level -1: 40 mg/day), Gilteritinib (Dose Level 1: 80 mg/day), Gilteritinib (Dose Level 2: 120 mg/day) |
Primary outcome
Dose-limiting toxicities (DLT) of gilteritinib when combined with mitoxantrone, cladribine, cytarabine and filgrastim (GM-CLAG)
Time frame: 42 days
DLT is defined as: * Any treatment-related death * Grade 4 neutropenia or thrombocytopenia lasting > 42 days from start of cycle in the absence of active AML * Any Grade 4 or greater ANC lasting past cycle day 42 * Any Grade 4 or greater platelets lasting past cycle day 42 * Grade ≥ 4 organ toxicity (i.e., adverse reactions involving neurologic, pulmonary, cardiac, gastrointestinal, genitourinary, renal, hepatic, or cutaneous systems.) * Confirmed Hy's law cases
Maximally Tolerated Dose (MTD) of gilteritinib when combined with mitoxantrone, cladribine, cytarabine and filgrastim (GM-CLAG)
Time frame: 42 days
The MTD will be defined as the highest dose of Gilteritinib estimated to have less than 20% hematologic or non-hematologic DLT rates. Enrollment of next patient will be allowed only after prior cohort has completed Cycle 1 and recovered or failure of response has been documented by Day 42.
9 secondary outcomes
Complete remission (CR) rate after completing induction chemotherapy with the GM-CLAG combination.
Time frame: 42 days
Complete remission with incomplete hematologic recovery (CRi) after completing induction chemotherapy with the GM-CLAG combination.
Time frame: 42 days
Complete remission with partial hematologic recovery (CRh) after completing induction chemotherapy with the GM-CLAG combination.
Time frame: 42 days
Composite complete remission (CRc) after completing induction chemotherapy with the GM-CLAG combination.
Time frame: 42 days
Minimal residual disease status (MRD) after completing induction chemotherapy with the GM-CLAG combination.
Time frame: Two Induction Cycles (each up to 42 days)
Best response to Induction Therapy
Time frame: Two Induction Cycles (each up to 42 days)
Percentage of patients proceeding to transplantation
Time frame: Up to 2 years
Overall survival (OS)
Time frame: Up to 2 years
Leukemia-free survival (LFS)
Time frame: Up to 2 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2023.
- Individual participant dataSharing planned: No
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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.
Ayman Qasrawi, MD principal investigator
University of Kentucky
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Gilteritinib 40 MG Oral Tablet, Cladribine and Cytarabine in people with Acute Myeloid Leukemia, run by Ayman H Qasrawi at 1 site in United States.
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 26 inclusion and 22 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: withdrawn, as of the sponsor's last update on 25 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Dose-limiting toxicities (DLT) of gilteritinib when combined with mitoxantrone, cladribine, cytarabine and filgrastim (GM-CLAG) (time frame: 42 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Apr 2023.