B-cell Adult Acute Lymphoblastic Leukemia, B-cell Childhood Acute Lymphoblastic Leukemia, B-cell Chronic Lymphocytic Leukemia, Childhood Burkitt Lymphoma, Childhood Diffuse Large Cell Lymphoma, Childhood Immunoblastic Large Cell Lymphoma, Cutaneous B-cell Non-Hodgkin Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Intraocular Lymphoma, Nodal Marginal Zone B-cell Lymphoma, Post-transplant Lymphoproliferative Disorder, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Grade III Lymphomatoid Granulomatosis, Recurrent Adult Hodgkin Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Grade III Lymphomatoid Granulomatosis, Recurrent Childhood Large Cell Lymphoma, Recurrent Childhood Lymphoblastic Lymphoma, Recurrent Childhood Small Noncleaved Cell Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent/Refractory Childhood Hodgkin Lymphoma, Recurrent Small Lymphocytic Lymphoma, Refractory Chronic Lymphocytic Leukemia, Refractory Hairy Cell Leukemia, Small Intestine Lymphoma, Splenic Marginal Zone Lymphoma, Testicular Lymphoma, Waldenström Macroglobulinemia
Conditions
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.
Interventions
Given IV
Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation
Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation
Correlative studies
Correlative studies
Sponsors
Study design
Eligibility
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Rituximab Pre- and Post-transplant) 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.
rituximab: Given IV
peripheral blood stem cell transplantation: Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation
nonmyeloablative allogeneic hematopoietic stem cell transplantation: Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation
pharmacological study: Correlative studies
laboratory biomarker analysis: Correlative studies | 63 |
| Total | 63 |
Baseline characteristics
| Characteristic | Treatment (Rituximab Pre- and Post-transplant) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 57 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 58 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 58 Participants |
| Region of Enrollment United States | 63 participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 63 |
| serious Total, serious adverse events | 5 / 63 |
Outcome results
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Rituximab Pre- and Post-transplant) | Disease Relapse Rate | 18 Participants |
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Rituximab Pre- and Post-transplant) | Incidence and Severity of Acute and Chronic GVHD Evaluated Per an Adapted Version of Common Terminology Criteria for Adverse Events (CTCAE) Version 2.0 | 17 Participants |
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
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Rituximab Pre- and Post-transplant) | Overall Survival and Progression-free Survival | PFS - 6 Months | 48 Participants |
| Treatment (Rituximab Pre- and Post-transplant) | Overall Survival and Progression-free Survival | PFS - 1 Year | 39 Participants |
| Treatment (Rituximab Pre- and Post-transplant) | Overall Survival and Progression-free Survival | PFS - 1.5 Years | 34 Participants |
| Treatment (Rituximab Pre- and Post-transplant) | Overall Survival and Progression-free Survival | OS - 6 Months | 52 Participants |
| Treatment (Rituximab Pre- and Post-transplant) | Overall Survival and Progression-free Survival | OS - 1 Year | 44 Participants |
| Treatment (Rituximab Pre- and Post-transplant) | Overall Survival and Progression-free Survival | OS - 1.5 Years | 36 Participants |
Rate of Graft Rejection and Graft Failure
Number of patients experiencing graft rejection and/or graft failure
Time frame: 18 Months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Rituximab Pre- and Post-transplant) | Rate of Graft Rejection and Graft Failure | Graft Rejection | 1 Participants |
| Treatment (Rituximab Pre- and Post-transplant) | Rate of Graft Rejection and Graft Failure | Graft Failure | 0 Participants |
Time to Engraftment
Median time from transplant to engraftment.
Time frame: 18 Months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Rituximab Pre- and Post-transplant) | Time to Engraftment | 10 Days |