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

Phase 2

Completed

Conditions: Intraocular Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Lymphoblastic Lymphoma
Recurrent Mantle Cell Lymphoma
Refractory Hairy Cell Leukemia
B-cell Adult Acute Lymphoblastic Leukemia
Childhood Diffuse Large Cell Lymphoma
Nodal Marginal Zone B-cell Lymphoma

Interventions: Biological: rituximab
Procedure: peripheral blood stem cell transplantation
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Other: pharmacological study
Other: laboratory biomarker analysis

Registration Number: NCT00867529

Lead Sponsor: Fred Hutchinson Cancer Center

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 63

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (rituximab pre- and post-transplant)	peripheral blood stem cell transplantation	Patients receive rituximab 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.
Treatment (rituximab pre- and post-transplant)	laboratory biomarker analysis	Patients receive rituximab 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.
Treatment (rituximab pre- and post-transplant)	nonmyeloablative allogeneic hematopoietic stem cell transplantation	Patients receive rituximab 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.
Treatment (rituximab pre- and post-transplant)	pharmacological study	Patients receive rituximab 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.
Treatment (rituximab pre- and post-transplant)	rituximab	Patients receive rituximab 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.

Primary Outcome Measures

Name	Time	Method
Disease Relapse Rate	At 18 months	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.

Secondary Outcome Measures

Name	Time	Method
Incidence and Severity of Acute and Chronic GVHD Evaluated Per an Adapted Version of Common Terminology Criteria for Adverse Events (CTCAE) Version 2.0	Through day +100 after transplant	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
Overall Survival and Progression-free Survival	At 6 months and then every year thereafter, up to 18 months	Number of patients surviving and number of patients surviving without progressive/relapsed disease, post-transplant.
Rate of Graft Rejection and Graft Failure	18 Months	Number of patients experiencing graft rejection and/or graft failure
Time to Engraftment	18 Months	Median time from transplant to engraftment.