Melphalan Hydrochloride in Treating Participants With Newly-Diagnosed Multiple Myeloma Undergoing Donor Stem Cell Transplantation
Melphalan Hydrochloride in Treating Participants With Newly-Diagnosed Multiple Myeloma Undergoing Donor Stem Cell Transplantation
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.
Inclusion Criteria:

 -  Patients with non-relapsed multiple myeloma in complete response (CR), partial
 remission (PR), very good partial remission (VGPR), or symptomatic stable disease (no
 evidence of progression) including patients with light chain multiple myeloma (MM)
 detected in the serum by free light chain assay OR

 -  Patients with non-secretory multiple myeloma (absence of a monoclonal protein [M
 protein] in serum as measured by electrophoresis [serum protein electrophoresis
 (SPEP)] and immunofixation (serum immunofixation electrophoresis [SIFE]) and the
 absence of Bence Jones protein in the urine [urine protein electrophoresis (UPEP)]
 defined by use of conventional electrophoresis and immunofixation [urine
 immunofixation electrophoresis (UIFE) techniques]) but with measurable disease on
 imaging studies like magnetic resonance imaging (MRI), computed tomography (CT) scan
 or positron emission tomography (PET) scan.

 -  Patients who have received at least two cycles of initial systemic therapy and are
 within 2 to 12 months of the first dose. Mobilization therapy is not considered
 initial therapy.

 -  Karnofsky performance score 70% or higher.

 -  Left ventricular ejection fraction at rest > 40% within 3 months of registration.

 -  Bilirubin < 2 x the upper limit of normal (except patients with Gilbert syndrome in
 whom bilirubin level of > 2 x upper normal limit will be allowed)

 -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x the upper
 limit of normal.

 -  Creatinine clearance of >= 40 mL/min, estimated or calculated using the
 Cockcroft-Gault equation.

 -  Pulmonary function: diffusing capacity of the lungs for carbon monoxide (DLCO), forced
 expiratory volume in one second (FEV1), forced vital capacity (FVC) > 50% of predicted
 value (corrected for hemoglobin) within 3 months of registration.

 -  All female and male subjects of reproductive potential must consent to the use of
 effective contraceptive methods as advised by the study doctor during treatment.

 -  Signed informed consent form.

 Exclusion Criteria:

 -  Patients with uncontrolled bacterial, viral or fungal infections (currently taking
 medication and progression of clinical symptoms).

 -  Patients seropositive for the human immunodeficiency virus (HIV).

 -  Patients with history of myocardial infarction within 6 months prior to enrollment or
 has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled
 angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence
 of acute ischemia or active conduction system abnormalities.

 -  Patients participating in an investigational new drug protocol within 14 days before
 enrollment.

 -  Female patients who are pregnant (positive beta-human chorionic gonadotropin [b-HCG])
 or breast feeding.

 -  Prior hematopoietic cell transplantation allogeneic or autologous (A prior autologous
 HCT will be allowed as long as it was part of tandem transplantation).

 -  Prior organ transplant requiring immunosuppressive therapy