Rituximab, Bendamustine Hydrochloride, Melphalan and Stem Cell Transplant in Treating Elderly Participants with Relapsed or Refractory B-cell Lymphoma

Status: Active

Description

This phase I / II trial studies the side effects and best dose of rituximab, bendamustine hydrochloride and melphalan and how well they work in treating elderly participants with B-cell Lymphoma that has come back or does not respond to treatment before undergoing stem cell transplant. Immunotherapy with monoclonal antibodies, such as rituximab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. 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.

Eligibility Criteria

Inclusion Criteria

  • PHASE I
  • Any B-cell non-Hodgkin lymphoma would be eligible for phase I portion of the study
  • PHASE II
  • Histologically confirmed diagnosis of 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 B-cell NHL can be enrolled; however, the progression-free survival (PFS) endpoint varies greatly amongst different types of lymphoma; in order to accurately interpret the survival data, 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
  • PHASE I AND II
  • Patients between the ages of 65 to 69 years old with a hematopoietic stem cell transplant comorbidity index (HCT-CI) >= 3
  • 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 >= 50 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

  • Disease progression by IWG criteria since last therapy
  • Patients with history of central nervous system (CNS) involvement
  • Prior autologous 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

Locations & Contacts

New York

New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Parastoo Bahrami Dahi
Phone: 212-639-5846

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To establish day +30 safety and toxicity of the combination chemo-immunotherapy regimen of rituximab/bendamustine hydrochloride (bendamustine)/melphalan (RBM) followed by reinfusion of autologous stem cell in elderly patients with B-cell non-Hodgkin lymphoma (NHL). (Phase I)

II. To investigate the efficacy of the RBM combination therapy in relapsed (rel)/refractory (ref) diffuse large B-cell lymphoma (DLBCL). (Phase II)

SECONDARY OBJECTIVES:

I. To estimate the remission rate (complete remission [CR] and CR+ partial remission [PR] proportion) at day +100. (Phase I+II)

II. To estimate overall survival (OS) at 12-months. (Phase I+II)

III. To estimate the cumulative incidence of progression and treatment-related mortality (TRM). (Phase I+II)

IV. To describe transplant toxicity over time (day +30) and its association with hematopoietic cell transplantation comorbidity index (HCT-CI). (Phase I+II)

V. To examine symptom-burden using the - M.D. Anderson Symptom Inventory (MDASI), and its association with cytokines on a Luminex immunoassay: IL-6 and CRP at days -10, 0, +7 and +14. (Phase I+II)

VI. 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]). (Phase I+II)

VII. To estimate neutrophil, lymphocyte and platelet recovery rates with this regimen. (Phase I+II)

VIII. Data for melphalan pharmacokinetic (PK) will be collected (Phase I+II)

OUTLINE:

Participants receive rituximab intravenously (IV) on days -11 and -4, bendamustine hydrochloride IV on days -3 and -2, and melphalan IV on day -1, then undergo stem cell transplant on day 0. If the participant has a CD20 negative tumor, rituximab can be omitted from the regimen.

After completion of study treatment, participants are followed up at 1, 3, 6, 9 and 12 months.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
Memorial Sloan Kettering Cancer Center

Principal Investigator
Parastoo Bahrami Dahi

Trial IDs

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