Status:
RECRUITING
Ivosidenib and Venetoclax With or Without Azacitidine in Treating Patients With IDH1 Mutated Hematologic Malignancies
Lead Sponsor:
M.D. Anderson Cancer Center
Conditions:
Acute Myeloid Leukemia
Hematopoietic and Lymphoid System Neoplasm
Eligibility:
All Genders
18+ years
Phase:
PHASE1
PHASE2
Brief Summary
This phase Ib/II trial studies the side effects and best dose of venetoclax and how well it works when given together with ivosidenib with or without azacitidine, in treating patients with IDH1-mutate...
Detailed Description
PRIMARY OBJECTIVES: I. To determine the safety and tolerability, maximum tolerated dose (MTD), and recommended phase 2 dose (RP2D) of the combination of ivosidenib with venetoclax, with or without th...
Eligibility Criteria
Inclusion
- Age \> 18 years.
- ECOG performance status of \< 2.
- IDH1-R132 mutated disease status as assessed by local laboratory. 2HG-producing IDH1 variants outside of R132 (i.e. R100) may be eligible after discussion with the PI.
- Relapsed/refractory AML, or treatment-naïve patients with AML who are not eligible for standard induction chemotherapy. Patients with high-risk MDS, MDS/MPN or MPN (defined as \> 10% bone marrow blasts, or intermediate or high risk by IPSS, R-IPSS or D-IPSS) that have failed standard therapy may also be eligible after discussion with the PI.
- Adequate hepatic function (direct bilirubin \< 2 x ULN, ALT and/or AST \< 3x ULN) unless deemed to be related to underlying leukemia.
- Adequate renal function including creatinine clearance \> 30 ml/min based on the Cockcroft-Gault equation.
- Willing and able to provide informed consent
- In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation will be at least 7 days for cytotoxic or non-cytotoxic (immunotherapy) agents.
- Male subjects must agree to refrain from unprotected sex and sperm donation from initial study drug administration until 90 days after the last dose of study drug.
Exclusion
- Patients with known allergy or hypersensitivity to ivosidenib or venetoclax.
- Patients who have previously received either ivosidenib or venetoclax.
- Patients with any concurrent uncontrolled clinically significant medical condition including infection, laboratory abnormality, or psychiatric illness, which could place the patient at unacceptable risk of study treatment.
- The use of other chemotherapeutic agents or anti-leukemic agents is not permitted during study with the following exceptions (1) intrathecal chemotherapy for prophylactic use or for controlled CNS leukemia. (2) use of hydroxyurea and/or one dose of cytarabine (up to 2 g/m2) for patients with rapidly proliferative disease is allowed before the start of study therapy and for the first four weeks on therapy.
- Patients receiving concomitant strong CYP3A inducers (avasimibe, carbamazepine, phenytoin, rifampin, rifabutin, St. John's wort) within 3 days of start of study therapy.
- Patients with active graft-versus-host-disease (GVHD) status post stem cell transplant (patients without active GVHD on chronic suppressive immunosuppression and/or phototherapy for chronic skin GVHD are permitted after discussion with the PI).
- Patients with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications.
- Patients with a concurrent active malignancy under treatment.
- QTc interval using Fridericia's formula (QTcF) \> 450 msec. Bundle branch block and prolonged QTc interval are permitted after discussion with the PI.
- Known active hepatitis B (HBV) or Hepatitis C (HCV) infection or known HIV infection.
- Subject has a white blood cell count \> 25 x 10⁹/L. (Note: Hydroxyurea is permitted to meet this criterion.)
- Nursing women, women of childbearing potential (WOCBP) with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception a. Appropriate highly effective method(s) of contraception include oral or injectable hormonal birth control, IUD, and double barrier methods (for example a condom in combination with a spermicide).
Key Trial Info
Start Date :
March 19 2018
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
September 30 2027
Estimated Enrollment :
96 Patients enrolled
Trial Details
Trial ID
NCT03471260
Start Date
March 19 2018
End Date
September 30 2027
Last Update
October 3 2025
Active Locations (4)
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1
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
2
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44195
3
Oregon Health and Science University
Portland, Oregon, United States, 97239
4
M D Anderson Cancer Center
Houston, Texas, United States, 77030