Total Marrow and Lymphoid Irradiation in Combination With Fludarabine and Melphalan as Conditioning for Allogeneic Peripheral Blood Stem Cell Hematopoietic Cell Transplant in Older Patients With Refractory and Relapsed Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome

Summary

This phase II trial tests the effect of total marrow and lymphoid irradiation (TMLI) in combination with fludarabine and melphalan as conditioning regimen in older patients with acute myeloid leukemia or high-risk myelodysplastic syndrome that has not responded to previous treatment (refractory) and that has come back after a period of improvement (relapsed) and are undergoing a donor (allogeneic) peripheral blood stem cell (PBSC) hematopoietic cell transplant (HCT) from a matched related or unrelated donor. HCT is the only curative treatment for high-risk patients, but the side effects related to the current conditioning treatments limit the use to younger and more fit patients. TMLI is a targeted form of total body radiation that uses intensity-modulated radiation therapy to target marrow, lymph node chains, and the spleen. It is designed to reduce radiation-associated side effects and maximize the radiation therapeutic effect. Fludarabine blocks cells from making deoxyribonucleic acid (DNA) and may kill cancer cells. It is a type of purine antagonist and a type of ribonucleotide reductase inhibitor. Melphalan is in a class of medications called alkylating agents. It may kill cancer cells by damaging their DNA and stopping them from dividing. Giving chemotherapy, such as fludarabine and melphalan, and TMLI before an allogeneic 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 healthy stem cells from a related or unrelated donor, such as PBSC HCT, that closely match the patient's blood, are infused into a patient, they may help the patient's bone marrow make more healthy cells and platelets, an may help destroy any remaining cancer cells. Giving TMLI in combination with fludarabine and melphalan as conditioning treatment for an allogeneic PBSC HCT from a matched related or unrelated donor may be safe, tolerable, and/or effective in treating high-risk older patients with relapsed and refractory acute myeloid leukemia or high-risk myelodysplastic syndrome.

Conditions

• Acute Myeloid Leukemia With Complex Karyotype
• Myelodysplastic Chronic Myelomonocytic Leukemia
• Myelodysplastic Syndrome
• Recurrent Acute Myeloid Leukemia
• Recurrent Myelodysplastic Chronic Myelomonocytic Leukemia
• Recurrent Myelodysplastic Syndrome
• Recurrent Secondary Acute Myeloid Leukemia
• Refractory Acute Myeloid Leukemia
• Refractory Myelodysplastic Chronic Myelomonocytic Leukemia
• Refractory Myelodysplastic Syndrome
• Refractory Secondary Acute Myeloid Leukemia

Interventions

PROCEDURE

Biospecimen Collection

Undergo urine and blood sample collection

PROCEDURE

Bone Marrow Biopsy

Undergo bone marrow biopsy

PROCEDURE

Computed Tomography

Undergo CT

PROCEDURE

Echocardiography Test

Undergo echocardiography

DRUG

Fludarabine Phosphate

Given IV

DRUG

Melphalan

Given IV

PROCEDURE

Multigated Acquisition Scan

Undergo MUGA

BIOLOGICAL

Palifermin

Given IV

PROCEDURE

Peripheral Blood Stem Cell Transplantation

Undergo allogeneic PBSC HCT

OTHER

Questionnaire Administration

Ancillary studies

DRUG

Sirolimus

Given sirolimus

DRUG

Tacrolimus

Given IV or PO

RADIATION

Total Marrow and Lymphoid Irradiation

Undergo TMLI

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• City of Hope Medical Center

  lead OTHER

Principal Investigators

• Monzr M Al Malki · City of Hope Medical Center

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2027-04-05

Primary Completion

2029-04-05

Completion

2029-04-05

FDA Drug

Yes

Countries

• United States

Study Locations