CPX-351 and Ivosidenib for the Treatment of IDH1 Mutated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
Acute Myeloid Leukemia With Gene Mutations, Myelodysplastic Syndrome, Myeloproliferative Neoplasm
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia With Gene Mutations
Eligibility Criteria
Inclusion Criteria:
- 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 >= 10% bone marrow blasts, or intermediate or high risk by International Prognostic Scoring System [IPSS], revised [R]-IPSS or dynamic [D]-IPSS) may also be eligible after discussion with the PI
- Direct bilirubin =< 2 x upper limit of normal (ULN) unless deemed to be related to underlying leukemia
- Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) =< 3 x ULN unless deemed to be related to underlying leukemia
- 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 Criteria:
- Patients who have previously received either ivosidenib or 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 central nervous system (CNS) leukemia. (2) use of hydroxyurea, and/or cytarabine (1 or 2 doses; up to 2 g/m^2) 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 (New York Heart Association [NYHA] class III or IV), unstable angina, or an ejection fraction < 45%
- Patients with prior anthracycline exposure of > 360 mg/m^2 daunorubicin (or equivalent) or > 210 mg/m^2 daunorubicin (or equivalent) in patients with prior mediastinal radiation
- Corrected QT (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
- Appropriate highly effective method(s) of contraception include oral or injectable hormonal birth control, intrauterine device (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
Sites / Locations
- M D Anderson Cancer CenterRecruiting
Arms of the Study
Arm 1
Experimental
Treatment (CPX-351, ivosidenib)
INDUCTION: Patients receive CPX-351 IV over 90 minutes on days 1, 3, and 5, and ivosidenib PO QD on days 1-28. Patients who do not achieve complete remission may receive a second cycle of induction therapy in the absence of disease progression or unacceptable toxicity. Patients achieving complete remission proceed to consolidation. CONSOLIDATION: Patients receive CPX-351 IV over 90 minutes on days 1 and 3, and ivosidenib PO QD on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive ivosidenib PO QD for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients who are experiencing clinical benefit and who have not experienced excessive toxicity after completion of 2 years of maintenance may be eligible to continue therapy after discussion with the principal investigator.