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

Part of paid clinical trials in Duarte, California.

Sponsor
City of Hope Medical Center
Study ID
NCT07582172
Phase
PHASE2
Status
Not Yet Recruiting

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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

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Biospecimen Collection — PROCEDURE
    Undergo urine and blood sample collection
  • Bone Marrow Biopsy — PROCEDURE
    Undergo bone marrow biopsy
  • Computed Tomography — PROCEDURE
    Undergo CT
  • Echocardiography Test — PROCEDURE
    Undergo echocardiography
  • Fludarabine Phosphate — DRUG
    Given IV
  • Melphalan — DRUG
    Given IV
  • Multigated Acquisition Scan — PROCEDURE
    Undergo MUGA
  • Palifermin — BIOLOGICAL
    Given IV
  • Peripheral Blood Stem Cell Transplantation — PROCEDURE
    Undergo allogeneic PBSC HCT
  • Questionnaire Administration — OTHER
    Ancillary studies
  • Sirolimus — DRUG
    Given sirolimus
  • Tacrolimus — DRUG
    Given IV or PO
  • Total Marrow and Lymphoid Irradiation — RADIATION
    Undergo TMLI

Study Details

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.

Key Dates

Start date
Apr 5, 2027
Status verified
May 2026
Primary completion
Apr 5, 2029
Completion
Apr 5, 2029

Study Design

Enrollment
35 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Treatment (TMLI, fludarabine, melphalan, allogeneic PBSC-HCT)
    Patients receive palifermin IV on days -11, -10, -9, 0, 1 and 2, fludarabine IV on days -4 to -2 and melphalan IV on day -2 and undergo TMLI BID for 8 fractions on days -8 to -5. Patients receive allogeneic PBSC-HCT on day 0. Starting on day -1, patients also receive tacrolimus IV or PO QD and sirolimus QD per standard of care. Additionally, patients undergo echocardiography or MUGA, CT, urine and blood sample collection, and bone marrow biopsy throughout the study.

Primary Outcome Measure

Leukemia-free survival [ Time Frame: From the date of stem cell infusion to the date of first observation of relapse/progression, or date of death, whichever comes first, assessed at 2 years post-hematopoietic cell transplantation (HCT) ]

Locations (1)

FacilityCityStateZIPSite coordinators
City of Hope Medical CenterDuarteCalifornia91010
Monzr M. Al Malki
[email protected]
626-218-2405
Monzr M. Al Malki (PRINCIPAL_INVESTIGATOR)

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