Intensity Modulated Total Marrow Irradiation, Fludarabine Phosphate, and Melphalan in Treating Patients With Relapsed Hematologic Cancers Undergoing a Second Donor Stem Cell Transplant

• Status: Recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This phase I trial studies the side effects and the best dose of intensity modulated total marrow irradiation (IMTMI) when given together with fludarabine phosphate and melphalan in treating patients with cancers of the blood (hematologic) that have returned after a period of improvement (relapsed) undergoing a second donor stem cell transplant. IMTMI is a type of radiation therapy to the bone marrow that may be less toxic and may also reduce the chances of cancer to return. Giving fludarabine phosphate, melphalan, and IMTMI before a donor stem cell transplant may help stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Chicago
• Collaborator: National Cancer Institute (NCI)
• Treatments: Fludarabine; Fludarabine phosphate; Melphalan; Mycophenolate mofetil; Mycophenolic Acid; Tacrolimus; Vidarabine

Criteria

Inclusion Criteria:

• Patients with the following diseases: acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS) undergoing second allogeneic (allo)-stem cell transplant (SCT) using the same donor or different donor for disease relapse; patients with other hematologic malignancies, including acute lymphoblastic leukemia (ALL), will be at the discretion of the investigators

• Karnofsky performance status of 70 or above

• Life expectancy is not severely limited by concomitant illness

• Adequate cardiac and pulmonary function; patients with decreased left ventricular ejection fraction (LVEF) =< 40% or diffusion capacity of carbon monoxide (DLCO) =< 50% of predicted will be evaluated by cardiology or pulmonary prior to enrollment on this protocol

• Serum creatinine =<1.5 mg/dL or creatinine clearance > 50 ml/min; some patients with minor deviations may be accepted on protocol after discussion with the principal investigator (PI)

• Serum bilirubin =< 2.0 mg/dl; some patients with minor deviations may be accepted on protocol after discussion with the PI

• Serum glutamic oxaloacetic transaminase (SGPT) < 5 x upper limit of normal; some patients with minor deviations may be accepted on protocol after discussion with the PI

• No evidence of chronic active hepatitis or cirrhosis

• Human immunodeficiency virus (HIV)-negative

• Patient is not pregnant

• Patient or guardian able to sign informed consent

• DONOR: Since these patients already had first allo-SCT; in the majority time, the same matched donor has been used for second allo-SCT; if the patients have multiple donors, alternative matched (8/8 or 10/10) donor could be used for the second allo-SCT; the donor could be matched related donors or matched unrelated donors from registry

• DONOR: If more than one potential volunteer unrelated donor is considered suitable, further selection of the most suitable donor will be prioritized as follows or will follow our institutional guideline from our stem cell transplant standard operating procedure (SOP):

• Age of donor (18-24 > 25-34 > 35-44 > 45+)

• Sex of donor (male > female, nulliparous female > parous, multiparous female)

• Cytomegalovirus (CMV) status, if recipient is CMV seronegative (CMV- > CMV+