NCT06928662

Chemotherapy (Decitabine in Combination With FLAG-Ida) and Total-Body Irradiation Followed by Donor Stem Cell Transplant for the Treatment of Adults With Myeloid Malignancies at High Risk of Relapse

Sequential Decitabine in Combination With FLAG-Ida Followed Immediately by Reduced-Intensity Conditioning (RIC) Allogeneic Hematopoietic Cell Transplantation (DEC-FLAG-Ida/RIC) for Adults With Myeloid Malignancies at High Risk of Relapse: A Phase 1/2 Study

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 36 (estimated)
• Sponsor: Fred Hutchinson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

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. These are chemotherapy drugs that work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Filgrastim is in a class of medications called colony-stimulating factors. It works by helping the body make more neutrophils, a type of white blood cell. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. TBI is radiation therapy to the entire body. Giving chemotherapy and TBI before a donor peripheral blood stem cell (PBSC) transplant helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. When the healthy stem cells from a donor are infused into a patient, they may help the patient's bone marrow make more healthy cells and platelets. Giving decitabine in combination with FLAG-Ida and TBI before donor PBSC transplant may work better than FLAG-Ida and TBI alone in treating adult patients with myeloid malignancies at high risk of relapse.

Detailed description

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. Patients then undergo HCT (receive donor PBSCs via infusion) on day 0. Patients also undergo multi-gated acquisition (MUGA) scan or echocardiography (ECHO) during screening, chest X-rays and bone marrow aspiration and/or biopsy during screening and as clinically indicated, and collection of blood samples throughout the study. After completion of study treatment, patients are followed up at 6 months, 1 year, and 2 years.

Conditions

• Acute Myeloid Leukemia
• Acute Undifferentiated Leukemia
• Mixed Phenotype Acute Leukemia
• Recurrent Acute Myeloid Leukemia
• Recurrent Acute Undifferentiated Leukemia
• Recurrent Chronic Myelomonocytic Leukemia
• Recurrent Mixed Phenotype Acute Leukemia
• Recurrent Myelodysplastic Syndrome
• Refractory Acute Myeloid Leukemia
• Refractory Acute Undifferentiated Leukemia
• Refractory Chronic Myelomonocytic Leukemia
• Refractory Mixed Phenotype Acute Leukemia
• Refractory Myelodysplastic Syndrome
• Secondary Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Decitabine	Given IV
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow aspiration and/or biopsies
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow aspiration and/or biopsies
PROCEDURE	Chest Radiography	Undergo chest X-rays
DRUG	Cytarabine	Given IV
PROCEDURE	Echocardiography Test	Undergo ECHO
BIOLOGICAL	Filgrastim	Given SC
DRUG	Fludarabine	Given IV
PROCEDURE	Hematopoietic Cell Transplantation	Given via infusion
DRUG	Idarubicin	Given IV
PROCEDURE	Multigated Acquisition Scan	Undergo MUGA
PROCEDURE	Pheresis	Undergo apheresis
RADIATION	Total-Body Irradiation	Undergo TBI
PROCEDURE	Biospecimen Collection	Undergo collection of blood

Timeline

• Start date: 2025-09-23
• Primary completion: 2028-03-09
• Completion: 2028-11-29
• First posted: 2025-04-15
• Last updated: 2025-11-06

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study