Bendamustine Hydrochloride and Melphalan before Stem Cell Transplant in Treating Elderly Patients with Multiple Myeloma or Relapsed or Refractory B-cell Lymphoma
- PHASE I
- Any patient with multiple myeloma or B-cell non-Hodgkin lymphoma would be eligible for phase I portion of the study
- DOSE EXPANSION ELIGIBILITY
- Histologically confirmed diagnosis of multiple myeloma or rel/ref DLBCL, or diffuse large B cell lymphoma transformed from an indolent lymphoma * Since the endpoint of the phase I portion is safety, any patient with myeloma or B-cell NHL can be enrolled; for dose expansion, patients with myeloma and B-NHL will be analyzed separately; the progression-free survival (PFS) endpoint varies greatly amongst different types of lymphoma; in order to accurately interpret the survival data as secondary endpoint, a homogeneous cohort of patients with DLBCL will be evaluated; DLBCL is the most aggressive B-NHL with limited options; other B-NHL’s are generally more indolent and have more options available to them
- ADDITIONAL ELIGIBILITY FOR BOTH THE PHASE I AND DOSE EXPANSION COHORT
- Patients between the ages of 65 to 69 years old with a hematopoietic stem cell transplant comorbidity index (HCT-CI) score of 3 or higher
- Any patient age 70 years old or older, irrespective of their hematopoietic stem cell transplant comorbidity index (HCT-CI) score
- Karnofsky performance status (KPS) >= 70
- Males must agree to use an acceptable form of contraception per institutional practices
- Complete or partial response to salvage chemotherapy by International Working Group (IWG) criteria
- Cardiac ejection fraction of >= 45%
- Hemoglobin-adjusted diffusing capacity of carbon monoxide (DLCO) of >= 45%
- Creatinine clearance of >= 40 mL/min
- Completion of most recent salvage therapy within 8 weeks of enrollment
- Direct bilirubin =< 2.0 mg/dL in the absence of suspected Gilbert’s disease (if Gilbert’s disease is suspected, the total bilirubin must be =< 3.0 mg/dL)
- Aspartate aminotransferase (AST) =< 2.5 upper limit of normal (ULN)
- In lymphoma: Disease progression by IWG criteria since last therapy
- Patients with history of central nervous system (CNS) involvement
- Prior autologous (only in lymphoma) or allogeneic stem cell transplantation
- Patients who have failed bendamustine-based regimen previously
- Patients within 6 months of myocardial infarction (MI) and stroke will be excluded
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)
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.
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.
Trial Phase Phase I
Trial Type Treatment
Memorial Sloan Kettering Cancer Center
Parastoo Bahrami Dahi
- Primary ID 17-373
- Secondary IDs NCI-2018-00160
- Clinicaltrials.gov ID NCT03352765