Rituximab in Treating Patients Undergoing Stem Cell Transplant for B-Cell Cancer That Has Relapsed or Not Responded to Treatment - Full Text View

Sponsors and Collaborators:	Fred Hutchinson Cancer Research Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00867529

Purpose

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer cell growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cell-killing substances to them. Giving rituximab before and after donor stem cell transplant may kill more hematologic cancer cells.

PURPOSE: This phase II trial is studying rituximab in treating patients undergoing stem cell transplant for B-cell cancer that has relapsed or not responded to treatment.

Condition	Intervention	Phase
Graft Versus Host Disease Leukemia Lymphoma Lymphoproliferative Disorder Multiple Myeloma and Plasma Cell Neoplasm Precancerous/Nonmalignant Condition Small Intestine Cancer	Biological: rituximab Genetic: polymorphism analysis Other: laboratory biomarker analysis Other: pharmacological study	Phase II

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Intestinal Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Lymphoma Multiple Myeloma

Drug Information available for: Rituximab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Addition of Pre- and Post-Transplant Rituximab to Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation in Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Relapse rate at 18 months [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival [ Designated as safety issue: No ]
Progression-free survival [ Designated as safety issue: No ]
Non-relapse mortality [ Designated as safety issue: No ]
Incidence and severity of acute and chronic graft-versus-host disease [ Designated as safety issue: Yes ]
Rate of graft rejection and graft failure [ Designated as safety issue: No ]
Time to engraftment [ Designated as safety issue: No ]
Incidence of serious adverse events [ Designated as safety issue: Yes ]
Pharmacokinetics of rituximab [ Designated as safety issue: No ]
Impact of FCγRIIIa receptor and CD32 polymorphisms on disease response and relapse [ Designated as safety issue: No ]
B-cell and T-cell immune reconstitution [ Designated as safety issue: No ]

Estimated Enrollment:	80
Study Start Date:	February 2009
Estimated Primary Completion Date:	February 2012 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

To determine the effect of addition of peri-transplant rituximab on relapse rate at 18 months in patients with relapsed or refractory CD20+ B-cell malignancies after undergoing nonmyeloablative allogeneic hematopoietic cell transplantation (HCT).

Secondary

To determine overall survival, progression-free survival, and non-relapse mortality of these patients.
To determine the incidence and severity of acute and chronic graft-versus-host disease in these patients.
To determine the rate of graft rejection and graft failure.
To determine the time to engraftment in these patients.
To determine the incidence of serious adverse events in these patients with the addition of rituximab.
To evaluate the pharmacokinetics of rituximab in the setting of nonmyeloablative allogeneic HCT.
To describe donor and host polymorphisms of the FCγRIIIa receptor and CD32 and evaluate their impact on disease response and relapse in these patients.
To describe B-cell and T-cell immune reconstitution in these patients.

OUTLINE: Patients undergo a total-body irradiation-based nonmyeloablative conditioning and allogeneic peripheral blood stem cell transplantation (PBSCT)* on their main treatment protocol.

NOTE: *Day 0 is the date of allogeneic PBSCT.

Patients receive pre- and post-transplantation rituximab IV on days -3, 10, 24, and 38.

Blood and bone marrow samples are collected periodically for biomarker studies. Samples are analyzed for the pharmacokinetics of rituximab, host polymorphisms of FCγRIIIa receptor and CD32, and other biomarker laboratory studies.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 30 patients with aggressive non-Hodgkin lymphoma and ≥ 50 patients with any other B-cell cancer will be accrued for this study.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of CD20-expressing B-cell malignancy
- Any histologic type or grade for which nonmyeloablative allogeneic transplantation is considered an appropriate treatment option
- Relapsed or refractory disease
Concurrently enrolled on a nonmyeloablative allogeneic hematopoietic cell transplantation protocol or standard treatment plan employing total body irradiation (TBI)-based conditioning of ≤ 4 Gy, with or without fludarabine
- Studies may include, but are not limited to, the following:
  - FHCRC-1813.00
  - FHCRC-1938.00
  - FHCRC-1898.00
  - FHCRC-1409.00
- Receiving unmodified peripheral blood mononuclear cell graft products
- Must have appropriate related or unrelated donor available (no HLA-haploidentical donors)
- No protocols involving bone marrow allografts

PATIENT CHARACTERISTICS:

Not pregnant or nursing
Fertile patients must use effective contraception during and for ≥ 12 months after completion of study treatment

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Enrollment in protocol FHCRC-1726.00 takes priority over this study for patients with chemorefractory aggressive non-Hodgkin lymphoma
Enrollment in protocol FHCRC-1711.00 or FHCRC-1840.00 takes priority over this study for patients with chronic lymphocytic leukemia

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00867529

Locations

United States, Washington
Fred Hutchinson Cancer Research Center	Recruiting
Seattle, Washington, United States, 98109
Contact: Andrew Rezvani, MD 206-667-1505 arezvani@fhcrc.org
Seattle Cancer Care Alliance	Recruiting
Seattle, Washington, United States, 98109-1023
Contact: Clinical Trials Office - Seattle Cancer Care Alliance 800-804-8824

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Andrew Rezvani, MD

Fred Hutchinson Cancer Research Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Fred Hutchinson Cancer Research Center ( Andrew Rezvani )
Study ID Numbers:	CDR0000637563, FHCRC-2226.00, IR-6884
Study First Received:	March 20, 2009
Last Updated:	March 28, 2009
ClinicalTrials.gov Identifier:	NCT00867529 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

graft versus host disease
recurrent adult Hodgkin lymphoma
recurrent/refractory childhood Hodgkin lymphoma
Waldenstrom macroglobulinemia
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult grade III lymphomatoid granulomatosis
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
Burkitt lymphoma
childhood diffuse large cell lymphoma

childhood grade III lymphomatoid granulomatosis
childhood immunoblastic large cell lymphoma
recurrent childhood grade III lymphomatoid granulomatosis
recurrent childhood large cell lymphoma
recurrent childhood lymphoblastic lymphoma
intraocular lymphoma
primary central nervous system lymphoma
post-transplant lymphoproliferative disorder
cutaneous B-cell non-Hodgkin lymphoma
adult grade III lymphomatoid granulomatosis
B-cell adult acute lymphoblastic leukemia
B-cell childhood acute lymphoblastic leukemia
recurrent adult acute lymphoblastic leukemia
recurrent childhood acute lymphoblastic leukemia
monoclonal B-cell lymphocytosis

Study placed in the following topic categories:

Lymphoma, Mantle-Cell
Mantle Cell Lymphoma
Follicular Lymphoma
Ileal Diseases
Duodenal Neoplasms
Graft Versus Host Disease
Leukemia, Prolymphocytic
Hemorrhagic Disorders
Leukemia, Lymphocytic, Chronic, B-Cell
Hodgkin Disease
Lymphoma, Large B-Cell, Diffuse
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Digestive System Neoplasms
Rituximab

Hematologic Diseases
Blood Coagulation Disorders
Hairy Cell Leukemia
Multiple Myeloma
Waldenstrom Macroglobulinemia
B-cell Lymphomas
Gastrointestinal Neoplasms
Lymphoma, Non-Hodgkin
Acute Lymphoblastic Leukemia, Childhood
Leukemia, Lymphoid
Immunologic Factors
Precancerous Conditions
Hodgkin Lymphoma, Childhood
Blood Protein Disorders
Gastrointestinal Diseases

Additional relevant MeSH terms:

Immunologic Factors
Precancerous Conditions
Antineoplastic Agents
Gastrointestinal Diseases
Blood Protein Disorders
Physiological Effects of Drugs
Paraproteinemias
Hemostatic Disorders
Ileal Diseases
Duodenal Neoplasms
Lymphoma, B-Cell
Leukemia
Neoplasms by Site
Hemorrhagic Disorders
Ileal Neoplasms

Jejunal Diseases
Therapeutic Uses
Cardiovascular Diseases
Lymphoma
Duodenal Diseases
Jejunal Neoplasms
Digestive System Neoplasms
Neoplasms by Histologic Type
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Hematologic Diseases
Vascular Diseases
Intestinal Diseases
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 07, 2009