Milademetan Tosylate and Low-Dose Cytarabine in Treating Participants With Recurrent or Refractory Acute Myeloid Leukemia
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|ClinicalTrials.gov Identifier: NCT03634228|
Recruitment Status : Recruiting
First Posted : August 16, 2018
Last Update Posted : July 15, 2019
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia TP53 wt Allele||Drug: Cytarabine Drug: Milademetan Tosylate||Phase 1 Phase 2|
I. To evaluate the safety and tolerability. (Phase 1) II. To determine the recommended phase II dose. (Phase I) III. To evaluate the efficacy (by International Working Group [IWG] criteria - Phase 2) of the MDM2 inhibitor, milademetan tosylate (DS-3032b), in combination with low dose cytarabine (LDAC) in relapsed/refractory (non-TP53 mutant) patient population.
I. Evaluation of time to response variables including overall survival (OS), event-free survival (EFS) and duration of response (DOR).
II. Determine biomarkers that may be predictive of DS-3032b (milademetan tosylate) activity.
III. Molecular profiling at screening, on study, and at relapse to determine genomic predictors of response and resistance.
OUTLINE: This is a dose escalation study of milademetan tosylate, followed by a phase II study.
Participants receive low dose cytarabine subcutaneously (SC) twice daily (BID) on days 1-7 and receive milademetan tosylate orally (PO) once daily (QD) on days 8-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment participants are followed up at 30 days.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||32 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Study of the Oral MDM2 Inhibitor DS-3032b in Combination With Low Dose Cytarabine (LDAC) in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML)|
|Actual Study Start Date :||December 17, 2018|
|Estimated Primary Completion Date :||May 1, 2020|
|Estimated Study Completion Date :||May 1, 2021|
Experimental: Treatment (low dose cytarabine, MDM2 inhibitor DS-3032b)
Participants receive low dose cytarabine SC BID on days 1-7 and receive milademetan tosylate PO QD on days 8-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Milademetan Tosylate
- Incidence of adverse events (Phase I) [ Time Frame: Up to 1 year ]Graded according to Common Terminology Criteria for Adverse Events version 5.0.
- Maximum tolerated dose (MTD) (Phase I) [ Time Frame: Up to 28 days ]As determined by dose limiting toxicity (DLT). MTD is defined the highest dose at which no more than one patient out of 6 patients experience DLTs in the first cycle. A 3+3 algorithm will be applied for dose escalation or dose de-escalation.
- Overall response rate (Phase II) [ Time Frame: Up to 28 days ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03634228
|Contact: Kiran Naqvifirstname.lastname@example.org|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Kiran Naqvi 713-745-6877|
|Principal Investigator: Kiran Naqvi|
|Principal Investigator:||Kiran Naqvi||M.D. Anderson Cancer Center|