Neoplasms, Myelogenous Leukemia, AcutePhase 1NCT02098967
A Study of the Safety and Pharmacokinetics of RO6839921, An MDM2 Antagonist, in Patients With Advanced Cancers, Including Acute Myeloid Leukemia.
A Phase 1 study testing RO6839921 in people with Neoplasms, Myelogenous Leukemia, Acute, run by Hoffmann-La Roche at 5 sites in 2 countries.
Trial summary
This open label, Phase I study of RO6839921 is a dose-escalation study with two arms. Prior to investigations in either arm, patients in a single cohort, Cohort 0, will receive non-escalating, intravenous (IV) doses of RO6839921 daily on Days 1-5 of a 28-day cycle. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms, Myelogenous Leukemia, Acute
- What is being tested?
- RO6839921
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 21 Apr 2014to 7 May 2018
- 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
- Cohort 0 and Arm A
- Patient must have histologically or cytologically confirmed advanced cancer for which standard cures or relieving measures either do not exist, are ineffective or are not acceptable to the patient.
- Measureable disease according to RECIST criteria version 1.1.
- ECOG performance status of 0 to 1.
- Adequate bone marrow function.
- Arm B
Show all 16Show fewer
- Patients with documented acute myeloid leukemia (AML), except for acute promyelocytic leukemia.
- Patients with relapsed/refractory AML or patients who have not received prior therapy who are high risk according to European LeukemiaNet (ELN) criteria.
- ECOG performance status of 0 to 2.
- For Cohort 0, Arms A and B
- Life expectancy of >/= 12 weeks.
- Age >/= 18 years or older.
- All patients must be willing to use effective methods of contraception until 10 days after the last dose; women must not be pregnant or breast-feeding.
- Adequate renal and hepatic function.
- Patients with stable central nervous system (CNS) tumors are eligible.
- There are no requirements or limitations on the amount or type of prior anti-tumor/anti-leukemia therapy.
Who cannot join
- Cohort 0 and Arm A
- Patients with a history of any form of leukemia except for Stage 0 and 1 chronic lymphocytic leukemia (CLL) not requiring treatment.
- Patients receiving any cancer treatment within 21 days of start of study medication. Patients must also have recovered from severe side effects due to prior treatment before study start.
- Patients with known bone marrow disorders that may interfere with bone marrow recovery, or patients with delayed recovery from prior chemoradiotherapy.
- Patients with known bleeding or clotting disorders or non-drug-induced low platelet count.
- Arm B
Show all 16Show fewer
- Patients receiving any cancer treatment within 14 days of start of study medication. Hydroxyurea may be taken until first administration of the study drug. Patients must also have recovered from severe side effects due to prior treatment before study start.
- For Cohort 0, Arms A and B
- Patients receiving any other test drugs within 30 days of start of study medication
- Patients receiving the cytochrome P450 inhibitors, substrates or inducers specified in the protocol.
- Anticoagulation or antiplatelet treatment must be discontinued 7 days prior to start of study medication.
- Patients who have received hormonal therapy (except for prostate cancer treatment and hormone replacement therapy) within the 2 weeks prior to start of study medication.
- Patients with evidence of electrolyte imbalance, which may be treated to meet eligibility.
- Serum albumin < 2.8 g/dL.
- HIV-positive patients who are currently receiving combination antiretroviral therapy.
- Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study.
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
United States3 sites
University of Colorado
Aurora, Colorado, 80045
Medical University of South Carolina; Hollings Cancer Center
Charleston, South Carolina, 29425
Washington University
St Louis, Missouri, 63110
Canada2 sites
Jewish General Hospital / McGill University
Montreal, Quebec, H3T 1E2
University Health Network; Princess Margaret Hospital; Medical Oncology Dept
Toronto, Ontario, M5G 2M9
About this study
Official title: A Multi-Center, Open-Label, First-in-Human, Phase I Dose-Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO6839921, An MDM2 Antagonist, Following Intravenous Administration in Patients With Advanced Malignancies, Including Acute Myeloid Leukemia (AML)
This open label, Phase I study of RO6839921 is a dose-escalation study with two arms. Prior to investigations in either arm, patients in a single cohort, Cohort 0, will receive non-escalating, intravenous (IV) doses of RO6839921 daily on Days 1-5 of a 28-day cycle. Interim PK and safety data from this cohort will be evaluated before initiating dose-escalation.
In arm A, RO6839921 will be given to patients with advanced solid tumor malignancies. In Arm B, RO6839921 will be given to patients with relapsed/refractory acute myeloid leukemia (AML). The arms will escalate independently. Escalation will begin in solid tumor patients (Arm A) in single patient cohorts, using a new Continual Reassessment Method (n-CRM). Escalation for AML patients will be initiated at or below the dose level that causes >/= Grade 2 hematologic side effects in Arm A. Escalation in AML patients will follow a rolling 6 design.
Read more
In both arms, RO6839921 will be administered by IV infusion on Days 1-5 of 28-day cycles.
There will be no intrapatient dose escalation. All patients may be treated until disease progression/relapse or unacceptable toxicity.
- Conditions
- Neoplasms, Myelogenous Leukemia, Acute
- Being tested
- RO6839921
- Medical subject headings
- Neoplasms, Leukemia, Myeloid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RO6839921Drug
Non-escalating IV doses given on Days 1-5 of Cycle 1.
RO6839921Drug
Escalating IV doses of RO6839921 in solid tumor patients. Dose escalation will be calculated using the new Continual Reassessment Method (nCRM). RO6839921 will be given on Days 1-5 of 28-day cycles. Treatment will continue until disease progression, unacceptable toxicity or study discontinuation.
RO6839921Drug
Escalating IV doses of RO6839921 in AML patients. Escalation will follow an adapted rolling 6 design. Starting dose </= dose inducing Grade 2 toxicity in patients with solid tumors. RO6839921 will be given on Days 1-5 of 28-day cycles. Treatment will continue until disease progression, unacceptable toxicity or study discontinuation.
| Study group | Role | What they receive |
|---|---|---|
| Acute myeloid leukemia patients | Experimental | Not described Receives: Drug: RO6839921 |
| Cohort 0 | Experimental | Not described Receives: Drug: RO6839921 |
| Solid tumor patients | Experimental | Not described Receives: Drug: RO6839921 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events
Measured: Approximately 1 year
Incidence of dose-limiting toxicities
Measured: Approximately 1 year
Secondary outcomes (2)
Plasma area under the concentration-time curve (AUC) of RO6839921.
Measured: Up to Day 22
Changes in serum macrophage inhibitory cytokine-1 (MIC-1) expression measured by enzyme-linked immunosorbent assay (ELISA)
Measured: Up to Day 22
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2014 (estimated)
- Study start21 Apr 2014
- Primary completion7 May 2018
- Study completion7 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Neoplasms, Myelogenous Leukemia, AcuteStudies 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 68 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
- NCT02098967
- Sponsor's protocol ID
- NP28903
- Other IDs
- RG7775
- Status last verified
- May 2018
- First submitted
- 25 Mar 2014
- Last updated
- 17 May 2018
- Results posted
- No
Publications
Uy GL, Assouline S, Young AM, Blotner S, Higgins B, Chen LC, Yee K. Phase 1 study of the MDM2 antagonist RO6839921 in patients with acute myeloid leukemia. Invest New Drugs. 2020 Oct;38(5):1430-1441. doi: 10.1007/s10637-020-00907-4. Epub 2020 Feb 4.
PubMed 32020437Abdul Razak AR, Miller WH Jr, Uy GL, Blotner S, Young AM, Higgins B, Chen LC, Gore L. A phase 1 study of the MDM2 antagonist RO6839921, a pegylated prodrug of idasanutlin, in patients with advanced solid tumors. Invest New Drugs. 2020 Aug;38(4):1156-1165. doi: 10.1007/s10637-019-00869-2. Epub 2019 Nov 16.
PubMed 31734832
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center, Open-Label, First-in-Human, Phase I Dose-Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO6839921, An MDM2 Antagonist, Following Intravenous Administration in Patients With Advanced Malignancies, Including Acute Myeloid Leukemia (AML)
- ClinicalTrials.gov ID
- NCT02098967
- Acronym / sponsor ID
- NP28903
- Conditions
- Neoplasms, Myelogenous Leukemia, Acute
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 21 Apr 2014 (actual)
- Primary completion
- 7 May 2018 (actual)
- Study completion
- 7 May 2018 (actual)
- First posted
- 28 Mar 2014 (estimated)
- 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.
This open label, Phase I study of RO6839921 is a dose-escalation study with two arms. Prior to investigations in either arm, patients in a single cohort, Cohort 0, will receive non-escalating, intravenous (IV) doses of RO6839921 daily on Days 1-5 of a 28-day cycle. Interim PK and safety data from this cohort will be evaluated before initiating dose-escalation.
In arm A, RO6839921 will be given to patients with advanced solid tumor malignancies. In Arm B, RO6839921 will be given to patients with relapsed/refractory acute myeloid leukemia (AML). The arms will escalate independently. Escalation will begin in solid tumor patients (Arm A) in single patient cohorts, using a new Continual Reassessment Method (n-CRM). Escalation for AML patients will be initiated at or below the dose level that causes >/= Grade 2 hematologic side effects in Arm A. Escalation in AML patients will follow a rolling 6 design.
In both arms, RO6839921 will be administered by IV infusion on Days 1-5 of 28-day cycles.
There will be no intrapatient dose escalation. All patients may be treated until disease progression/relapse or unacceptable toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Acute myeloid leukemia patients | Experimental | Drug: RO6839921 |
| Cohort 0 | Experimental | Drug: RO6839921 |
| Solid tumor patients | Experimental | Drug: RO6839921 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Cohort 0 and Arm A
- Patient must have histologically or cytologically confirmed advanced cancer for which standard cures or relieving measures either do not exist, are ineffective or are not acceptable to the patient.
- Measureable disease according to RECIST criteria version 1.1.
- ECOG performance status of 0 to 1.
- Adequate bone marrow function.
Key exclusion criteria (16 listed)
- Cohort 0 and Arm A
- Patients with a history of any form of leukemia except for Stage 0 and 1 chronic lymphocytic leukemia (CLL) not requiring treatment.
- Patients receiving any cancer treatment within 21 days of start of study medication. Patients must also have recovered from severe side effects due to prior treatment before study start.
- Patients with known bone marrow disorders that may interfere with bone marrow recovery, or patients with delayed recovery from prior chemoradiotherapy.
- Patients with known bleeding or clotting disorders or non-drug-induced low platelet count.
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 |
|---|---|---|
| RO6839921Non-escalating IV doses given on Days 1-5 of Cycle 1. | Drug | Cohort 0 |
| RO6839921Escalating IV doses of RO6839921 in solid tumor patients. Dose escalation will be calculated using the new Continual Reassessment Method (nCRM). RO6839921 will be given on Days 1-5 of 28-day cycles. Treatment will continue until disease progression, unacceptable toxicity or study discontinuation. | Drug | Solid tumor patients |
| RO6839921Escalating IV doses of RO6839921 in AML patients. Escalation will follow an adapted rolling 6 design. Starting dose </= dose inducing Grade 2 toxicity in patients with solid tumors. RO6839921 will be given on Days 1-5 of 28-day cycles. Treatment will continue until disease progression, unacceptable toxicity or study discontinuation. | Drug | Acute myeloid leukemia patients |
Primary outcome
Incidence of adverse events
Time frame: Approximately 1 year
Incidence of dose-limiting toxicities
Time frame: Approximately 1 year
2 secondary outcomes
Plasma area under the concentration-time curve (AUC) of RO6839921.
Time frame: Up to Day 22
Changes in serum macrophage inhibitory cytokine-1 (MIC-1) expression measured by enzyme-linked immunosorbent assay (ELISA)
Time frame: Up to Day 22
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2018.
- Derived from this study: PubMed 32020437Uy GL, Assouline S, Young AM, Blotner S, Higgins B, Chen LC, Yee K. Phase 1 study of the MDM2 antagonist RO6839921 in patients with acute myeloid leukemia. Invest New Drugs. 2020 Oct;38(5):1430-1441. doi: 10.1007/s10637-020-00907-4. Epub 2020 Feb 4.
- Derived from this study: PubMed 31734832Abdul Razak AR, Miller WH Jr, Uy GL, Blotner S, Young AM, Higgins B, Chen LC, Gore L. A phase 1 study of the MDM2 antagonist RO6839921, a pegylated prodrug of idasanutlin, in patients with advanced solid tumors. Invest New Drugs. 2020 Aug;38(4):1156-1165. doi: 10.1007/s10637-019-00869-2. Epub 2019 Nov 16.
Related trials for Neoplasms, Myelogenous Leukemia, Acute
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 1/2
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome
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
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RO6839921 in people with Neoplasms, Myelogenous Leukemia, Acute, run by Hoffmann-La Roche at 5 sites in 2 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 16 inclusion and 16 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: finished, as of the sponsor's last update on 17 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Canada. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Incidence of adverse events (time frame: Approximately 1 year). 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?
On the ClinicalTrials.gov record for NCT02098967, which also lists 2 linked publications.
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 17 May 2018.