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

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.

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

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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center

  lead OTHER

Principal Investigators

• Naveed Ali, MD · Fred Hutch/University of Washington Cancer Consortium

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-09-23

Primary Completion

2028-03-09

Completion

2028-11-29

FDA Drug

Yes

Countries

• United States

Study Locations