This phase I/II trial studies the side effects and best dose of melphalan hydrochloride in treating participants with newly-diagnosed multiple myeloma who are undergoing a donor stem cell transplantation. Giving chemotherapy before a donor stem cell transplantation helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the participant, they may help the participant's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Giving melphalan hydrochloride before a donor stem cell transplantation may work better than standard chemotherapy in helping to prevent multiple myeloma from coming back.
PRIMARY OBJECTIVES: I. To determine the optimal dose and schedule of melphalan for injection (melphalan hydrochloride \[Evomela\]) prior to autologous hematopoietic stem cell transplantation (auto-HCT) for multiple myeloma (MM). II. To collect the pharmacokinetic data and compare the exposure-response evaluations between the 2 infusion schedules. SECONDARY OBJECTIVES: I. To determine the incidence of treatment related mortality (TRM) at day 90 after auto-HCT in newly diagnosed myeloma patients treated on different schedules and doses of Evomela. II. To determine the rate of minimal residual disease (MRD) negative complete response (CR) rate at day 90 after auto-HCT in newly diagnosed myeloma patients treated on different schedules and doses of Evomela. III. To determine the progression-free survival (PFS) after auto-HCT in newly diagnosed myeloma patients treated on different schedules and doses of Evomela. OUTLINE: This is a phase I, dose escalation study of melphalan hydrochloride followed by a phase II study. PREPARATIVE REGIMEN: Participants are randomized to 1 of 2 groups. GROUP 1: Participants receive melphalan hydrochloride intravenously (IV) over 30-60 minutes on day -2. GROUP 2: Participants receive melphalan hydrochloride IV over 8-9 hours on day -2. TRANSPLANT: Participants in both groups undergo donor stem cell transplantation IV on day 0 over 30-60 minutes. POST-TRANSPLANT: Participants in both groups receive filgrastim-sndz subcutaneously (SC) once daily (QD) starting on day 5 and continuing in the absence of disease progression, unacceptable toxicity, or until evidence of an absolute neutrophil count (ANC) of 0.5 x 10\^9/L. After completion of study treatment, participants are followed up at 3 months, every 3 months for 1 year, and then annually for 1 year.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
62
M D Anderson Cancer Center
Houston, Texas, United States
Optimal Dose and Schedule of Evomela Prior to Autologous Transplant.
Dose limiting toxicity will be defined as grade 4 mucositis or any grade 4 or 5 non-hematologic or non-infectious toxicity occurring within 30 days from the start of infusion.
Time frame: Within 30 days after the start of infusion
Progression-free Survival (PFS)
Number of participants that are still alive and disease free one year post autologous transplant.
Time frame: From the date of Evomela injection up to 1 year
Treatment Related Mortality (TRM).
Number of participants expired from non-disease relapse within 90 days post transplant
Time frame: At day 90 post-transplant
Number of Participants That Have Achieved Complete Response (CR).
Number of participants that have achieved Complete response (CR). Complete response definition is negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow aspirates.
Time frame: At 90 days post-transplant
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