Milademetan Plus Quizartinib Combination Study in FLT3-ITD Mutant Acute Myeloid Leukemia (AML)
| Status: | Recruiting |
|---|---|
| Conditions: | Blood Cancer, Blood Cancer, Hematology |
| Therapuetic Areas: | Hematology, Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 2/14/2019 |
| Start Date: | August 27, 2018 |
| End Date: | October 15, 2021 |
A Phase 1 Study of Milademetan in Combination With Quizartinib in Subjects With FLT3-ITD Mutant Acute Myeloid Leukemia That Are Relapsed/Refractory, or Newly Diagnosed and Unfit for Intensive Chemotherapy
Participants with AML that has gone into remission and come back (relapsed) or gone into
remission with a number of leukemia cells still in their system (refractory) will be
recruited for this study. They will also have a biomarker called FLT3 in their blood.
Participants will receive a combined dose of quizartinib and another experimental drug that
has not been approved by the US Food and Drug Administration yet (m).
The combination of these drugs will be provided in different amounts on defined days (dosing
schedules).
It is expected that the combination of milademetan and quizartinib will be safe and well
tolerated. It is expected that the combination may fight the leukemia better than a single
drug.
The study will run for approximately 3 years. There may be up to 156 participants.
The study has 2 parts:
- Part 1 will test approximately 24-36 participants in 10 study centers in the United
States. Participants will receive two study drugs (milademetan and quizartinib) in
different amounts on specific days. Information will be gathered to see what dosing
schedule of the drug combination is best (maximum tolerated/recommended dose).
- Part 2 of the study will confirm the recommended dosing schedule identified in Part 1 is
effective. A larger number of participants will receive the recommended dose in up to an
additional 15 sites worldwide as necessary, based on the enrollment rate, the
population, and the standard of care available to them at the time.
remission with a number of leukemia cells still in their system (refractory) will be
recruited for this study. They will also have a biomarker called FLT3 in their blood.
Participants will receive a combined dose of quizartinib and another experimental drug that
has not been approved by the US Food and Drug Administration yet (m).
The combination of these drugs will be provided in different amounts on defined days (dosing
schedules).
It is expected that the combination of milademetan and quizartinib will be safe and well
tolerated. It is expected that the combination may fight the leukemia better than a single
drug.
The study will run for approximately 3 years. There may be up to 156 participants.
The study has 2 parts:
- Part 1 will test approximately 24-36 participants in 10 study centers in the United
States. Participants will receive two study drugs (milademetan and quizartinib) in
different amounts on specific days. Information will be gathered to see what dosing
schedule of the drug combination is best (maximum tolerated/recommended dose).
- Part 2 of the study will confirm the recommended dosing schedule identified in Part 1 is
effective. A larger number of participants will receive the recommended dose in up to an
additional 15 sites worldwide as necessary, based on the enrollment rate, the
population, and the standard of care available to them at the time.
Inclusion Criteria:
- Has reached the age of majority in their country
- Part 1 (dose escalation): Has FLT3-ITD mutant (≥ 3% FLT3-ITD/total FLT3) AML (primary
AML or secondary to myelodysplastic syndrome [MDS]) that have failed any prior
induction therapy regimen or have relapsed after prior induction/consolidation
therapy, and have not received more than three salvage therapies
- Part 2 (dose expansion): Has FLT3-ITD mutant (≥3% FLT3-ITD/total FLT3) AML (primary
AML or secondary to myelodysplastic syndrome [MDS]) that have failed any prior
induction therapy regimen or have relapsed after prior induction/consolidation
therapy, have not received more than one prior salvage therapy, and have not received
more than one FLT3 inhibitor during prior AML treatment(s)
- Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- Has protocol-defined adequate renal, hepatic and cardiac status
- Is not pregnant, and if not postmenopausal or a surgically sterile male or female, is
willing to use a highly effective contraceptive method upon enrollment, during the
course of the study, and for 3 months following the last dose of investigational drug
- Is willing to abstain from grapefruit and Seville oranges (or juice) from 7 days
before the first dose until study completion
- Is able and willing to provide protocol-defined bone marrow biopsies/aspirates
Inclusion Criteria for Cohort 2 in Part 2 only:
- FLT3-ITD mutant (≥ 3% FLT3-ITD/total FLT3) AML (primary AML or secondary to MDS) is
ineligible for intensive induction chemotherapy by meeting at least 1 of the
protocol-defined criteria
Exclusion Criteria:
- Has central nervous system (CNS) involvement of leukemia - patients with a history of
CNS leukemia may be eligible if the CNS leukemia is adequately controlled (defined as
no clinical symptoms of CNS disease and at least 2 consecutive lumbar punctures with
no evidence of disease prior to study enrollment) after discussion and approval from
the Sponsor
- Has acute promyelocytic leukemia (AML subtype M3)
- Has uncontrolled or significant cardiovascular disease
- Has an uncontrolled infection requiring intravenous antibiotics, antivirals, or
antifungals.
- Has known human immunodeficiency virus (HIV) infection, or active hepatitis B or C
infection based on positive tests during Screening
- Has persistent, clinically significant > Grade 1 non-hematologic toxicity from prior
AML therapies
- Has any history or medical condition, metastatic condition, drug/medication use or
other condition that might, per protocol or in the opinion of the investigator,
compromise:
1. safety or well-being of the participant or offspring
2. safety of study staff
3. analysis of results
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