Intensity Modulated Total Marrow Irradiation, Fludarabine Phosphate, and Melphalan in Treating Patients with Relapsed Hematologic Cancers Undergoing a Second or above Donor Stem Cell Transplant
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 or above 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.
- Patients with the following diseases: acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS) undergoing second or above 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 with discussion with the principal investigator (PI)
- Karnofsky performance status of 70 or above
- Life expectancy is not severely limited by concomitant illness in the opinion of the treating investigator
- 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; patient with left ventricular assist device (LVAD) placement without heart failure symptoms will be allowed
- 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 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 able to sign informed consent
Locations & Contacts
Contact: Hongtao Liu
Trial Objectives and Outline
I. To determine the maximum tolerated dose (MTD) of intensity-modulate total marrow irradiation (IMTMI) in combination with fludarabine (fludarabine phosphate)/melphalan as conditioning for second or above allogeneic stem cell transplantation for patients with hematologic malignancies.
I. To determine the overall toxicity and day 100 transplant related mortality after second or above allogeneic hematopoietic stem cell transplantation conditioned with increasing doses of intensity-modulate total marrow irradiation (IMTMI) in combination with fludarabine/melphalan.
II. To determine the time to neutrophil and platelet engraftment after second or above allogeneic hematopoietic stem cell transplantation conditioned with increasing doses of intensity-modulate total marrow irradiation (IMTMI) in combination with fludarabine/melphalan.
III. To determine the overall survival (OS) and event-free-survival (EFS) in patients with hematologic undergoing second or above allogeneic hematopoietic stem cell transplant (HSCT) after conditioning with fludarabine/melphalan and IMTMI.
IV. To determine the value of 18F-fluoro-L-thymidine-positron emission tomography (PET)/computed tomography (CT) (FLT-PET/CT) prior and after conditioning with fludarabine/melphalan and IMTMI to predict response and disease relapse. (Biomarker study)
V. To determine if IM-TMI with fludarabine + melphalan conditioning will eliminate minimal residual disease after SCT. (Biomarker study)
OUTLINE: This is a dose-escalation study of IMTMI.
FLT-PET/CT: Patients may undergo FLT-PET/CT scan on days -8 and -1.
CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes daily on days -7 to -3 and melphalan IV on day -2. Patients also undergo IMTMI twice daily (BID) for 2 to 5 days between days -7 to -3.
TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant (PBSCT) or bone marrow transplant (BMT) on day 0.
GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive tacrolimus IV continuously over 24 hours or orally (PO) BID on days -2 to 180 with taper thereafter and mycophenolate mofetil IV every 8 hours or PO on days 0-28 (for matched donors) or days 0-40 (for alternative donors) with taper to day 60. Patients with mis-matched donors also receive anti-thymocyte globulin (ATG) IV on days -5, -3, and -1.
After completion of treatment, patients are followed up periodically for 1 year and then yearly for 2 years.
Trial Phase & Type
University of Chicago Comprehensive Cancer Center
Secondary IDs NCI-2014-02469
Clinicaltrials.gov ID NCT02333162