Acute Myeloid Leukemia MedDRA version: 20.0 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: CPI-613
Product Code: CPI-613
Pharmaceutical Form: Solution for injection
INN or Proposed INN: devimistat (Rafael Pharmaceuticals)
CAS Number: 95809-78-2
Current Sponsor code: CPI-613
Ot
Sponsors
Rafael Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males and females age = 60 years must have histologically documented AML that is relapsed from, or refractory to, prior standard therapies. 2. Refractory is defined as failure to achieve CR or complete remission with incomplete recovery (CRi) following: -Two standard dose Cytarabine based induction cycles or one High Dose Cytarabine (HiDAC) based cycle, or -Failure to respond to one cycle of either standard dose or HiDAC; defined as no decrease in marrow blast percentage from diagnosis on Day 14 marrow), or -No response after at least 3 cycles of a hypomethylating agent (azacytidine or decitabine). 3. Relapse is defined as development of recurrent AML (Döhner et al. 2010; 115[3]:453-474) after CR or CRi has been achieved with a prior chemotherapy or after disease progression on a hypomethylating agent. 4. ECOG PS (performance score) 0-2. 5. Expected survival >3 months. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 400
Exclusion criteria
Exclusion criteria: 1. Patients who have received previous cytotoxic chemotherapy treatment for their relapsed or refractory AML. Previous treatment with hypomethylating agents (decitabine or azacytidine) either alone or in combination with Venetoclax is allowed. Targeted therapies including FLT3 or IDH1/2 inhibitors or Hydrea are allowed. Targeted therapies and Hydrea may be taken until the day prior to starting CHAM or HAM therapy. 2. Female patients who are pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 6 months after the last dose of CHAM or HAM therapy (the teratogenic potential of CPI-613 is unknown). Female patients of childbearing potential with a positive pregnancy test assessed by a serum pregnancy test at Screening. 3. Patients receiving any other standard or investigational treatment for AML, or any other investigational agent for any indication within the past 2 weeks prior to initiation of CPI-613 treatment (the use of Hydrea and/or oral tyrosine kinase inhibitors FLT3 or IDH 1/2 inhibitors is allowed until the day prior to starting CHAM or HAM therapy). Previous exposure to a hypomethylating agent either alone or in combination with Venetoclax is allowed. 4. Patients who have received immunotherapy of any type within the past 2 weeks prior to initiation of CPI-613 treatment. 5. Requirement for immediate palliative treatment of any kind including minor surgery. 6. Patients who have received a chemotherapy regimen with autologous stem cell support (bone marrow transplantation) within 6 months of starting CHAM or HAM therapy. 7. Patients who have had allogenic bone marrow transplantation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine efficacy of CHAM in terms of complete remission (CR) and compare with HAM (control). CR will be determined as per standard response criteria for AML (Döhner et al. 2010; 115[3]:453-474).;Secondary Objective: 1. To determine efficacy of CHAM in terms of overall survival (OS) and complete remission with partial hematologic recovery (CRh) as the two key secondary objectives to compare with HAM (control). The OS and CRh will be determined as per standard response criteria for AML (Döhner et al. 2010; 115[3]:453-474). 2. Safety: The assessment of safety will be based mainly on the frequency of adverse events (AEs) based on the Common Terminology Criteria for AEs (version 5.0 or later) grade. Adverse events will be coded according to the Medical Dictionary for Regulatory Activities. The safety outcomes will include the occurrence of at least one serious AE, of at least one Grade 3/4 AE, and of at least one AE requiring the discontinuation of study treatment. Electrocardiogram QTc intervals will also be evaluated. ;Primary end point(s): CR (Complete Remission).;Timepoint(s) of evaluation of this end point: 1st Interim Analysis, 2nd Interim Analysis and Final Analysis | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. OS (key secondary) 2. CRh (key secondary) 3. Safety 4. PK 5. PRO by EORTC QLQ C30 6. Cancer-associated mutations and/or genetic alterations in bone marrow aspirate/biopsy and/or peripheral blood. ;Timepoint(s) of evaluation of this end point: End of study | — |
Countries
Australia, Austria, Belgium, Canada, France, Germany, Italy, Korea, Republic of, Poland, Spain, United States
Contacts
Public ContactClinical Operations
Rafael Pharmaceuticals, Inc.
Outcome results
None listed