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

• ClinicalTrials.gov Identifier: NCT00867529
• Recruitment Status: Completed
• First Posted: March 23, 2009
• Results First Posted: May 22, 2017
• Last Update Posted: January 2, 2018
• Sponsor: Fred Hutchinson Cancer Research Center
• Collaborators: American Cancer Society, Inc.; National Cancer Institute (NCI)
• Information provided by (Responsible Party): David Maloney, Fred Hutchinson Cancer Research Center

Tracking Information

• First Submitted Date: March 20, 2009
• First Posted Date: March 23, 2009
• Results First Submitted Date: April 14, 2017
• Results First Posted Date: May 22, 2017
• Last Update Posted Date: January 2, 2018
• Study Start Date: February 2009
• Actual Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 5, 2017)

Disease Relapse Rate [ Time Frame: 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.

• Original Primary Outcome Measures (submitted: March 20, 2009): Relapse rate at 18 months

Current Secondary Outcome Measures (submitted: December 5, 2017)

• Incidence and Severity of Acute and Chronic GVHD Evaluated Per an Adapted Version of Common Terminology Criteria for Adverse Events (CTCAE) Version 2.0 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 18 Months ]
  Number of patients experiencing graft rejection and/or graft failure
• Time to Engraftment [ Time Frame: 18 Months ]
  Median time from transplant to engraftment.

Original Secondary Outcome Measures (submitted: March 20, 2009)

• Overall survival
• Progression-free survival
• Non-relapse mortality
• Incidence and severity of acute and chronic graft-versus-host disease
• Rate of graft rejection and graft failure
• Time to engraftment
• Incidence of serious adverse events
• Pharmacokinetics of rituximab
• Impact of FCγRIIIa receptor and CD32 polymorphisms on disease response and relapse
• B-cell and T-cell immune reconstitution

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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

Intervention

• Biological: rituximab
  Given IV
  Other Names:

  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
• Procedure: peripheral blood stem cell transplantation
  Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation
  Other Names:

  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
• Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
  Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation
• Other: pharmacological study
  Correlative studies
  Other Name: pharmacological studies
• Other: laboratory biomarker analysis
  Correlative studies

Study Arms

Experimental: 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.

Interventions:

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

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 14, 2017): 63
• Original Estimated Enrollment (submitted: March 20, 2009): 80
• Actual Study Completion Date: March 26, 2015
• Actual Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00867529
• Other Study ID Numbers: 2226.00; NCI-2010-00107 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 2226; 2226.00 ( Other Identifier: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium ); P01CA078902 ( U.S. NIH Grant/Contract ); P30CA015704 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: David Maloney, Fred Hutchinson Cancer Research Center
• Study Sponsor: Fred Hutchinson Cancer Research Center

Collaborators

• American Cancer Society, Inc.
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: David Maloney; Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

• PRS Account: Fred Hutchinson Cancer Research Center
• Verification Date: December 2017