Rituximab in Treating Patients Undergoing Donor Peripheral Blood Stem Cell Transplant for Relapsed or Refractory B-cell Lymphoma
Primary Purpose
B-cell Adult Acute Lymphoblastic Leukemia, B-cell Childhood Acute Lymphoblastic Leukemia, B-cell Chronic Lymphocytic Leukemia
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
rituximab
peripheral blood stem cell transplantation
nonmyeloablative allogeneic hematopoietic stem cell transplantation
pharmacological study
laboratory biomarker analysis
Sponsored by
About this trial
This is an interventional treatment trial for B-cell Adult Acute Lymphoblastic Leukemia
Eligibility Criteria
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
Sites / Locations
- Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (rituximab pre- and post-transplant)
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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
Overall Survival and Progression-free Survival
Number of patients surviving and number of patients surviving without progressive/relapsed disease, post-transplant.
Rate of Graft Rejection and Graft Failure
Number of patients experiencing graft rejection and/or graft failure
Time to Engraftment
Median time from transplant to engraftment.
Full Information
NCT ID
NCT00867529
First Posted
March 20, 2009
Last Updated
December 5, 2017
Sponsor
Fred Hutchinson Cancer Center
Collaborators
American Cancer Society, Inc., National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00867529
Brief Title
Rituximab in Treating Patients Undergoing Donor Peripheral Blood Stem Cell Transplant for Relapsed or Refractory B-cell Lymphoma
Official Title
Addition of Pre- and Post-Transplant Rituximab for Patients Undergoing Non-myeloablative Allogeneic Hematopoietic Cell Transplantation With Relapsed or Refractory CD20+ B-Cell Malignancies
Study Type
Interventional
2. Study Status
Record Verification Date
December 2017
Overall Recruitment Status
Completed
Study Start Date
February 2009 (undefined)
Primary Completion Date
March 2015 (Actual)
Study Completion Date
March 26, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fred Hutchinson Cancer Center
Collaborators
American Cancer Society, Inc., National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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 Small Lymphocytic Lymphoma, Recurrent/Refractory Childhood Hodgkin Lymphoma, Refractory Chronic Lymphocytic Leukemia, Refractory Hairy Cell Leukemia, Small Intestine Lymphoma, Splenic Marginal Zone Lymphoma, Testicular Lymphoma, Waldenström Macroglobulinemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
63 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment (rituximab pre- and post-transplant)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
rituximab
Other Intervention Name(s)
IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Other Intervention Name(s)
PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Intervention Description
Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation
Intervention Type
Procedure
Intervention Name(s)
nonmyeloablative allogeneic hematopoietic stem cell transplantation
Intervention Description
Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation
Intervention Type
Other
Intervention Name(s)
pharmacological study
Other Intervention Name(s)
pharmacological studies
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Disease Relapse Rate
Description
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 Outcome Measure Information:
Title
Incidence and Severity of Acute and Chronic GVHD Evaluated Per an Adapted Version of Common Terminology Criteria for Adverse Events (CTCAE) Version 2.0
Description
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
Title
Overall Survival and Progression-free Survival
Description
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
Title
Rate of Graft Rejection and Graft Failure
Description
Number of patients experiencing graft rejection and/or graft failure
Time Frame
18 Months
Title
Time to Engraftment
Description
Median time from transplant to engraftment.
Time Frame
18 Months
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Maloney
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
31481800
Citation
Shadman M, Maloney DG, Storer B, Sandmaier BM, Chauncey TR, Smedegaard Andersen N, Niederwieser D, Shizuru J, Bruno B, Pulsipher MA, Maziarz RT, Agura ED, Hari P, Langston AA, Maris MB, McSweeney PA, Storb R, Sorror ML. Rituximab-based allogeneic transplant for chronic lymphocytic leukemia with comparison to historical experience. Bone Marrow Transplant. 2020 Jan;55(1):172-181. doi: 10.1038/s41409-019-0660-8. Epub 2019 Sep 3.
Results Reference
derived
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Rituximab in Treating Patients Undergoing Donor Peripheral Blood Stem Cell Transplant for Relapsed or Refractory B-cell Lymphoma
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