Decitabine + FLAG-Ida and Total-Body Irradiation

Undergo bone marrow aspiration and/or biopsies

OUTLINE: This is a phase I, dose-escalation study of decitabine in combination with FLAG-Ida, TBI, and HCT followed by a phase II study. DONORS: Participants undergo apheresis for collection of PBSCs on study.

PATIENTS: Patients receive decitabine intravenously (IV) daily over 1 hour on days -12 to -10, -14 to -10, -16 to -10, or -19 to -10, filgrastim subcutaneously (SC) daily on days -9 to -4, idarubicin IV over 60 minutes daily on days -8 to -6, fludarabine IV over 30 minutes daily on days -8 to -4, cytarabine IV over 2 hours daily on days -8 to -4, and undergo TBI twice daily (BID) on day -1 or 0 OR daily on days -1 and 0 in the absence of disease progression or unacceptable toxicity.

This phase I/II trial studies the safety, side effects, and best dose of decitabine in combination with fludarabine, cytarabine, filgrastim, and idarubicin (FLAG-Ida) and total body irradiation (TBI) followed by a donor stem cell transplant in treating adult patients with cancers of blood-forming cells of the bone marrow (myeloid malignancies) that are at high risk of coming back after treatment (relapse).

Cancers eligible for this trial are acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and chronic myelomonocytic leukemia (CMML). Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. The FLAG-Ida regimen consists of the following drugs: fludarabine, cytarabine, filgrastim, and idarubicin.

Registro actualizado en ClinicalTrials.gov →

• Age ≥ 18 years with an HCT-co-morbidity index (CI) ≤ 5 for patients over 60 years.
• AML (2022 World Health Organization [WHO] criteria) that is either primary refractory (as defined by failure of 2 cycles of 7+3-like chemotherapy, 1 cycle of high-dose cytarabine-based chemotherapy, or at least 2 cycles of venetoclax in combination with other therapies) or is in untreated or unsuccessfully treated first or subsequent relapse. Patients in morphologic remission (i.e. < 5% blasts in the bone marrow) but evidence of minimal residual disease (MRD) by multiparameter flow cytometry, cytogenetics/fluorescence in situ hybridization (FISH), or molecular means will be eligible for trial participation. Patients with relapsed or refractory acute leukemia of ambiguous lineage (acute undifferentiated leukemia or mixed phenotype acute leukemia) that is either primary refractory or is in untreated or unsuccessfully treated first or subsequent relapse are also eligible.
• MDS and CMML: Subjects with previously treated MDS and CMML, defined as prior treatment with at least one hypomethylating agent (hypomethylating agent [HMA]; azacitidine, decitabine and/or decitabine-cedazuridine) whose disease progressed, relapsed, or was refractory to HMA treatment as follows: 1) patients who have failed at least 4 cycles of monotherapy with azacitidine, decitabine or decitabine-cedazuridine, 2) patients who received at least 2 cycles of HMA in combination with another therapeutic agent. Subjects with MDS and CMML who failed at least 1 cycle of induction chemotherapy will be also eligible. Patients with MDS or CMML who progress to secondary AML will be eligible if they received at least 4 cycles of HMA alone or 2 cycles of HMA in combination with another therapeutic agent.
• Patients may have previously received hypomethylating agents or chemotherapy with a mitoxantrone, idarubicin- or cladribine/fludarabine-based regimen for MDS or AML. If the patient has received cladribine-cytarabine-filgrastim-mitoxantrone (CLAG-M) or FLAG-Ida before and has been sensitive to this regimen, defined as MRD negative complete remission (CR) immediately after receiving the treatment and which lasts ≥ 1 year, eligibility will be determined on a case-by-case basis by the study principal investigator (PI).
• The use of hydroxyurea prior to initiation of study treatment is allowed. Patients with symptoms/signs of hyperleukocytosis, white blood cells (WBC) > 100,000/μL or with concern for other complications of high tumor burden of high tumor dynamics (e.g. disseminated intravascular coagulation) can be treated with leukapheresis or may receive up to 2 doses of cytarabine (up to 500 mg/m^2 per dose) prior to start of study treatment.
• Karnofsky score ≥ 70; Eastern Cooperative Oncology Group (ECOG) 0-1.

Criterios de inclusión tal como figuran en el registro, recortados. La lista completa, con las exclusiones, está en el registro actualizado.