The purpose of this study is to see if Multiple Myeloma (MM) cells are sensitive to the chemotherapy used in transplant or not. The main chemotherapy agent utilized in stem cell transplant is melphalan. The study will utilize 1/10 of the dose used in transplant to study sensitivity of the tumor to melphalan. Melphalan is approved by the U.S. Food and Drug Administration (FDA) for transplant for MM patients.
Currently, there is no method to predict whether a patient will have benefit from stem cell transplant or not. The usual approach is to proceed to stem cell transplant as long as a patient with MM has adequate organ function, meaning heart, kidney, lungs and other organs can tolerate the complications from transplant. In this study, all participants will already have had pre-collection bone marrow aspirate as standard of care that will be available for minimal residual disease (MRD) testing by NGS platform. Participants will receive only one, low-dose of melphalan (Evomela) intravenously. Participants will be asked to return to clinic for a follow-up visit at one week and two weeks after the infusion. Another bone marrow aspirate will be performed after 2 weeks from the day of Evomela administration. After the study, participants will have a standard-of-care (SOC) autologous stem cell transplant. The primary objective is to evaluate the impact of a test dose of low dose melphalan (16 mg/m2) before autologous hematopoietic cell transplant on disease volume measured by Next Generation Sequencing (NGS). Secondary objectives are: * To assess safety of low dose melphalan after CD34 (cluster of differentiation 34) collection and before high-dose melphalan-based autologous stem cell transplant. * To describe the impact of a test dose of low dose melphalan (16 mg/m2) before autologous hematopoietic cell transplant on disease volume measured by peripheral blood Mass Spectrometry.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
16 mg/m\^2 Evomela administered one time via a central line
Next Generation Sequencing
10mg once intravenous (IV) within 30 minutes before Evomela
University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States
Residual myeloma cell number measured by NGS
Myeloma disease response will be assessed by residual myeloma cell number measured via NGS method, utilizing clonoSEQ (assay) before and after low dose Evomela. The clonoSEQ Assay measures minimal residual disease (MRD) to monitor changes in burden of disease during and after treatment. MRD refers to the number of MM cells that remain in a person during and following treatment.
Time frame: At baseline
Residual myeloma cell number measured by NGS
Myeloma disease response will be assessed by residual myeloma cell number measured via NGS method, utilizing clonoSEQ before and after low dose Evomela. The clonoSEQ Assay measures minimal residual disease (MRD) to monitor changes in burden of disease during and after treatment. MRD refers to the number of MM cells that remain in a person during and following treatment.
Time frame: After treatment, day 15
Toxicity in pre-transplant period assessed according to CTCAE v. 5.0
Toxicity in pre-transplant period assessed according to Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0.
Time frame: Days 1, 8, 15, and 52
Percent of participants with pre-transplant period safety
Safety will be assessed by absence of any grade 4 or 5 clinically relevant therapy-related toxicity, or grade 3 clinically significant, therapy-related toxicities that do not resolve to grade ≤ 2 within one week
Time frame: Days 1, 8, 15, and 52
Percent of participants with diarrhea and oral mucositis and other non-hematologic toxicities
Percent of participants with diarrhea and oral mucositis and other non-hematologic toxicities will be assessed according to CTCAE v.5.0 during the inpatient transplant phase.
Time frame: Day 52
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
650 mg once orally within 30 minutes before Evomela
50 mg once intravenously within 30 minutes before Evomela
Percent of participants with post-transplant period safety
Safety assessed by absence of any grade 4 or higher diarrhea or oral mucositis lasting more than 2 days.
Time frame: Day 52
Percent of participants with engraftment failure
Neutrophil engraftment will be defined as the first day of 3 consecutive lab values obtained on different days when the ANC (absolute neutrophil count) is greater than or equal to 0.5 x 109/L (500/μl). Any Engraftment later than 28 days after hematopoietic stem cell infusion will count as engraftment failure.
Time frame: Day 52
Percent of participants with safety stopping endpoints
The following study drug-related toxicities, assessed based on CTCAE v.5.0, will count as safety stopping endpoints for this trial: 1. non-hematologic toxicity grade 3 or higher that do not resolve to ≤grade 2 within one week occurring in any patient at any time during the study; 2. any grade 4 toxicity in two or more patients with any duration in the pre-transplant phase and 3. any oral mucositis or diarrhea grade 4 toxicity in two or more patients last more than 2 days in the inpatient transplant phase. 4. Neutrophil engraftment failure in more than 2 patients (10% of enrolled patients), and 5. any death on trial whether in pre-transplant or post-transplant phase.
Time frame: Day 52