This phase I trial investigates the side effects of bendamustine hydrochloride and melphalan in treating elderly patients with multiple myeloma or B-cell Lymphoma that has come back (relapsed) or does not respond to treatment (refractory) before undergoing stem cell transplant. Drugs used in chemotherapy, such as bendamustine hydrochloride and melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before a transplant helps kill any cancer cells that are in the body and helps make room in the patient’s bone marrow for new blood-forming cells (stem cells) to grow.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03352765.
PRIMARY OBJECTIVES:
I. To establish day +30 safety and toxicity of the combination conditioning regimen of bendamustine hydrochloride (bendamustine) and melphalan followed by reinfusion of autologous stem cell in elderly patients with multiple myeloma (MM) or B-cell non-Hodgkin lymphoma (NHL). (Phase I)
II. To further describe the safety and tolerability of bendamustine (Benda)/melphalan (Mel) (+/- rituximab) in relapsed (rel)/refractory (ref) diffuse large B-cell lymphoma (DLBCL). (Dose expansion)
III. To further describe the safety and tolerability of Benda/Mel in MM. (Dose expansion)
SECONDARY OBJECTIVES:
I. To estimate the remission rate (complete remission [CR], partial remission [PR], very good partial response [VGPR] at day +100 in multiple myeloma.
II. To estimate the rate of progression-free survival (PFS) at 12-months in lymphoma.
III. To estimate overall survival (OS) at 12-months.
IV. To estimate the cumulative incidence of progression and treatment-related mortality (TRM).
V. To describe transplant toxicity over time (day +30) and its association with hematopoietic cell transplantation comorbidity index (HCT-CI).
VI. To examine symptom-burden using the - M.D. Anderson Symptom Inventory (MDASI), and its association with cytokines on a Luminex immunoassay: IL-6 and C-reactive protein (CRP) at days -10, 0, +7, +14, and +30.
VII. To describe geriatric assessment over time (before transplant, days +30 and +100 post-transplant) (activities of daily living [ADL] and instrumental activities of daily living [iADL]).
VIII. To estimate neutrophil, lymphocyte and platelet recovery rates with this regimen.
IX. Data for melphalan pharmacokinetic (PK) will be collected.
OUTLINE:
Patients receive bendamustine hydrochloride IV on days -3 and -2, and melphalan IV on day -1, then undergo stem cell transplant on day 0.
After completion of study treatment, patients are followed up at 1, 3, 6, 9 and 12 months.
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorParastoo Bahrami Dahi
