Rituximab in Treating Patients Undergoing Donor Peripheral Blood Stem Cell Transplant for Relapsed or Refractory B-cell Lymphoma

Fred Hutchinson Cancer Center63 enrolled

Overview

This phase II trial studies giving rituximab before and after a donor peripheral blood stem cell transplant in patients with B-cell lymphoma that does not respond to treatment (refractory) or has come back after a period of improvement (relapsed). Monoclonal antibodies, such as rituximab, can interfere with the ability of cancer cells to grow and spread. Giving rituximab before and after a donor peripheral blood stem cell transplant may help stop cancer from coming back and may help keep the patient's immune system from rejecting the donor's stem cells.

PRIMARY OBJECTIVES: I. To determine the effect of addition of peri-transplant rituximab on relapse rate at 18 months after non-myeloablative allogeneic hematopoietic cell transplant (HCT) for cluster of differentiation (CD)20+ B-cell malignancies. SECONDARY OBJECTIVES: I. To determine overall and progression-free survival and non-relapse mortality. II. To determine the incidence and severity of acute and chronic graft-versus-host disease (GVHD). III. To determine the rate of graft rejection and graft failure. IV. To determine the time to engraftment. V. To determine the incidence of serious adverse events with the addition of rituximab. VI. To evaluate the pharmacokinetics of rituximab in the setting of non-myeloablative allogeneic HCT. VII. To describe donor and host polymorphisms of the FC gamma receptor IIIa (FCg RIIIA) and CD32 and evaluate their impact on disease response and relapse. OUTLINE: Patients receive rituximab intravenously (IV), pre- and post-transplant, on days -3, 10, 24, and 38. Patients undergo donor peripheral blood stem cell transplant on day 0. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically for 18 months and then annually for 5 years.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Interventions

rituximabBIOLOGICAL

Given IV

peripheral blood stem cell transplantationPROCEDURE

Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation

nonmyeloablative allogeneic hematopoietic stem cell transplantationPROCEDURE

Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation

pharmacological studyOTHER

Correlative studies

laboratory biomarker analysisOTHER

Correlative studies

Eligibility

Sex: ALL

Medical Language ↔ Plain English

Inclusion Criteria: * With a diagnosis of CD20-expressing B-cell malignancy of any histologic type or grade for whom non-myeloablative allogeneic transplant is considered an appropriate treatment option * Who are enrolled on a non-myeloablative allogeneic HCT protocol employing total-body irradiation (TBI)-based conditioning of =\< 4.5 Gy, with or without fludarabine; this protocol may be used as an adjunct to the allogeneic arm of a tandem autologous/allogeneic transplant protocol, provided the allogeneic conditioning meets the above criteria * Receiving unmodified peripheral blood mononuclear cell graft products * With an appropriate related or unrelated donor; human leukocyte antigen (HLA)-haploidentical donors are excluded * Able to give informed consent (if \>= 18 years of age), or with a legal guardian capable of giving consent (if \< 18 years of age) Exclusion Criteria: * Ineligible for non-myeloablative allogeneic HCT * Receiving an HLA-haploidentical allograft * Who are fertile but unwilling to use contraception during and for at least 12 months after HCT * Females who are pregnant or breast-feeding

Outcomes

Primary Outcomes

Disease Relapse Rate

Number of patients with relapsed/progressive disease post-transplant. The effectiveness of pre- and post-transplant rituximab in decreasing the rate of relapse will be evaluated.

Time frame: At 18 months

Secondary Outcomes

Incidence and Severity of Acute and Chronic GVHD Evaluated Per an Adapted Version of Common Terminology Criteria for Adverse Events (CTCAE) Version 2.0

Number of patients who developed acute/chronic GVHD post-transplant. A chronic GVHD diagnosis ≥1 manifestation that is distinctive for chronic GVHD, as opposed to acute GVHD. aGVHD Stages Skin: a maculopapular eruption involving \< 25% BSA a maculopapular eruption involving 25 - 50% BSA generalized erythroderma generalized erythroderma with bullous formation and often with desquamation Liver: bilirubin 2.0 - 3.0 mg/100 mL bilirubin 3 - 5.9 mg/100 mL bilirubin 6 - 14.9 mg/100 mL bilirubin \> 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death

Time frame: Through day +100 after transplant

Overall Survival and Progression-free Survival

Number of patients surviving and number of patients surviving without progressive/relapsed disease, post-transplant.

Time frame: At 6 months and then every year thereafter, up to 18 months

Rate of Graft Rejection and Graft Failure

Number of patients experiencing graft rejection and/or graft failure

Time frame: 18 Months

Time to Engraftment

Median time from transplant to engraftment.