Status:
RECRUITING
CPX-351 and Ivosidenib for the Treatment of IDH1 Mutated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
Lead Sponsor:
M.D. Anderson Cancer Center
Conditions:
Acute Myeloid Leukemia With Gene Mutations
Myelodysplastic Syndrome
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
This phase II trial investigates how well CPX-351 and ivosidenib work in treating patients with acute myeloid leukemia or high-risk myelodysplastic syndrome that has IDH1 mutation. The safety of this ...
Detailed Description
PRIMARY OBJECTIVE: I. To determine the overall response rate (ORR) including CR, CRh, CRi, MLFS, and PR of the combination of CPX-351 and ivosidenib in IDH1-mutated patients with AML or high-risk MDS...
Eligibility Criteria
Inclusion
- Eastern Cooperative Oncology Group (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 principal investigator (PI)
- Treatment naive or relapsed/refractory AML who are eligible for intensive chemotherapy. Patients with high-risk MDS or MPN (defined as International Prognostic Scoring System Revised \[IPSS-R\] score ≥ 4 or dynamic \[D\]-IPSS ≥ 3) may also be eligible after discussion with the PI
- Adequate hepatic function (direct bilirubin ≤ 2 x upper limit of normal (ULN), Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 3 x 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 who have previously received CPX-351.
- 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 cytarabine (1 or 2 doses; up to 2 g/m2) for patients with rapidly proliferative disease is allowed before the 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 symptomatic congestive heart failure (NYHA Class III or IV), unstable angina, or an ejection fraction \< 45%.
- Patients with prior anthracycline exposure of \> 360 mg/m2 daunorubicin (or equivalent), or \> 210 mg/m2 daunorubicin (or equivalent) in patients with prior mediastinal radiation.
- QTc interval using Fridericia's formula (QTcF) \> 470 msec. A prolonged QTc interval in the setting of right bundle branch block is permitted after discussion with the PI.
- Nursing women, women of childbearing potential (WOCBP) with positive urine or serum 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).
- Subjects with a known medical history of progressive multifocal leukoencephalopathy (PML).
- Subjects taking strong CYP3A4 inducers are excluded from the study unless they can be transferred to other medications within ≥ 5 half-lives prior to dosing
- Patients with a diagnosis of acute promyelocytic leukemia (APL).
- Unresolved toxicities \> grade 1 from prior treatment including chemotherapy, targeted therapy, immunotherapy, experimental agents, radiation, or surgery.
Key Trial Info
Start Date :
December 30 2020
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
June 1 2026
Estimated Enrollment :
30 Patients enrolled
Trial Details
Trial ID
NCT04493164
Start Date
December 30 2020
End Date
June 1 2026
Last Update
November 21 2025
Active Locations (1)
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1
M D Anderson Cancer Center
Houston, Texas, United States, 77030