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Bendamustine Hydrochloride and Melphalan before Stem Cell Transplant in Treating Elderly Patients with Multiple Myeloma or Relapsed or Refractory B-cell Lymphoma

Trial Status: Active

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.

Inclusion Criteria

  • 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)

Exclusion Criteria

  • 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

New York

New York
Memorial Sloan Kettering Cancer Center
Status: ACTIVE
Contact: Parastoo Bahrami Dahi
Phone: 646-608-3733

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.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Parastoo Bahrami Dahi

  • Primary ID 17-373
  • Secondary IDs NCI-2018-00160
  • Clinicaltrials.gov ID NCT03352765