Irradiated Donor Lymphocytes and Rituximab in Treating Patients With Relapsed or Refractory Lymphoproliferative Disease

NCT ID: NCT00176475

Last Updated: 2013-09-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

2 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-01-31

Study Completion Date

2008-02-29

Brief Summary

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RATIONALE: When irradiated lymphocytes from a donor are infused into the patient they may help the patient's immune system kill cancer cells. Monoclonal antibodies, such as rituximab, can block cancer 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 cancer-killing substances to them. Giving irradiated donor lymphocytes together with rituximab may kill more cancer cells.

PURPOSE: This clinical trial is studying the side effects and how well giving irradiated donor lymphocytes together with rituximab works in treating patients with relapsed or refractory lymphoproliferative disease.

Detailed Description

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OBJECTIVES:

Primary

* Determine the toxicity of irradiated HLA-partially matched related donor lymphocytes when administered with rituximab in patients with relapsed or refractory CD20-positive lymphoproliferative disease.
* Determine the efficacy of this regimen in these patients.

Secondary

* Correlate response with Fc receptor FcγIIIA polymorphisms or predicted HLA-directed natural killer cell reactivity.

OUTLINE: This is a pilot study.

* Rituximab therapy: Patients receive rituximab IV on days -1, 6, 13, and 20. Treatment repeats approximately every 4 months in the absence of disease progression or unacceptable toxicity.
* Donor lymphocyte infusion: Patients receive irradiated donor lymphocytes IV over 1 hour on day 0. Treatment repeats every 8-16 weeks (alternating with courses of rituximab therapy) for up to 6 donor lymphocyte infusions in the absence of disease progression or unacceptable toxicity.

Peripheral blood is collected periodically during study for correlative laboratory studies. Blood samples are analyzed for FcγIIIA polymorphism by fluorescent in situ hybridization or by reverse transcriptase-polymerase chain reaction. Survival of donor lymphocytes is assessed by chimerism studies.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Conditions

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Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm

Keywords

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extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue nodal marginal zone B-cell lymphoma recurrent adult Burkitt lymphoma recurrent adult diffuse large cell lymphoma recurrent adult Hodgkin lymphoma recurrent adult lymphoblastic lymphoma recurrent adult acute lymphoblastic leukemia refractory chronic lymphocytic leukemia recurrent small lymphocytic lymphoma refractory hairy cell leukemia prolymphocytic leukemia recurrent marginal zone lymphoma recurrent grade 1 follicular lymphoma recurrent grade 2 follicular lymphoma recurrent grade 3 follicular lymphoma refractory multiple myeloma recurrent mantle cell lymphoma recurrent adult grade III lymphomatoid granulomatosis Waldenstrom macroglobulinemia splenic marginal zone lymphoma stage II multiple myeloma stage III multiple myeloma stage IV adult Burkitt lymphoma stage IV adult diffuse large cell lymphoma stage IV adult Hodgkin lymphoma stage IV adult lymphoblastic lymphoma stage III adult Burkitt lymphoma stage III adult diffuse large cell lymphoma stage III adult Hodgkin lymphoma stage III adult lymphoblastic lymphoma stage III grade 1 follicular lymphoma stage III grade 2 follicular lymphoma stage III grade 3 follicular lymphoma stage IV grade 1 follicular lymphoma stage IV grade 2 follicular lymphoma stage IV grade 3 follicular lymphoma stage III mantle cell lymphoma stage IV mantle cell lymphoma stage III marginal zone lymphoma stage IV marginal zone lymphoma stage III small lymphocytic lymphoma stage IV small lymphocytic lymphoma stage III chronic lymphocytic leukemia stage IV chronic lymphocytic leukemia progressive hairy cell leukemia, initial treatment

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Therapeutic allogeneic lymphocytes with rituximab

Group Type EXPERIMENTAL

rituximab

Intervention Type BIOLOGICAL

Patients will receive a single day infusion of standard dose rituximab (375 mg/m2) on days -1, 6, 13, 20 approximately every 4 months (in conjunction with alternating doses of the lymphocyte infusion).

therapeutic allogeneic lymphocytes

Intervention Type BIOLOGICAL

The product will then be assigned to the specific patient and the released product will be transported to and administered to the patient at CINJ, after premedication of the patient with acetaminophen 650 mg PO and diphenhydramine- HCl 25 mg PO. Blood product administration will be every 8 weeks and undertaken according to CINJ standard procedures

Interventions

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rituximab

Patients will receive a single day infusion of standard dose rituximab (375 mg/m2) on days -1, 6, 13, 20 approximately every 4 months (in conjunction with alternating doses of the lymphocyte infusion).

Intervention Type BIOLOGICAL

therapeutic allogeneic lymphocytes

The product will then be assigned to the specific patient and the released product will be transported to and administered to the patient at CINJ, after premedication of the patient with acetaminophen 650 mg PO and diphenhydramine- HCl 25 mg PO. Blood product administration will be every 8 weeks and undertaken according to CINJ standard procedures

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* Received prior anti-CD52 monoclonal antibody therapy and relapsed within 1 year of treatment OR ineligible to receive such therapy (for patients without symptomatic lymphadenopathy)
* Has documentation of disease-associated symptoms, rapid disease progression, or other indications for treatment
* B-cell prolymphocytic leukemia meeting any of the following criteria:

* Received prior fludarabine phosphate- or alkylating agent-containing regimens and relapsed within 1 year of treatment OR ineligible to receive such therapy due to comorbidities or allergies
* Received prior anti-CD52 monoclonal antibody therapy OR ineligible to receive such therapy (for patients without symptomatic lymphadenopathy)
* Lymphoplasmacytic lymphoma, marginal zone lymphoma, mucosa-associated lymphoid tissue lymphoma, or follicular lymphoma meeting any of the following criteria:

* Received prior fludarabine phosphate- and/or alkylating agent-containing regimens and relapsed within 1 year of treatment OR ineligible to receive such therapy due to comorbidities or allergies
* Received prior anti-CD20 monoclonal antibody therapy and relapsed within 1 year of treatment OR ineligible to receive such therapy
* Received prior radioconjugated anti-CD20 monoclonal antibody therapy OR ineligible to receive such therapy
* Has documentation of disease-associated symptoms, rapid disease progression, or other indications for treatment
* Multiple myeloma meeting any of the following criteria:

* Received prior alkylating agent-, thalidomide-, corticosteroid-, or bortezomib-containing regimens and relapsed after 1 year of treatment OR ineligible to receive such therapies due to comorbidities or allergies
* Received prior high-dose chemotherapy followed by autologous hematopoietic stem cell rescue and relapsed after treatment OR ineligible to receive such therapy
* Mantle cell lymphoma meeting the following criteria:

* Received prior combination chemotherapy and anti-CD20 monoclonal antibody therapy and relapsed after treatment OR ineligible to receive such therapy
* Diffuse large B-cell lymphoma meeting any of the following criteria:

* Received prior combination chemotherapy and relapsed after treatment OR ineligible to receive such therapy
* Received prior salvage combination chemotherapy with or without high-dose chemotherapy followed by autologous hematopoietic stem cell rescue and relapsed after treatment OR not a candidate to receive such therapy
* Received prior radiolabeled anti-CD20 monoclonal antibody therapy for transformed large cell lymphoma OR ineligible to receive such therapy
* Burkitt's lymphoma meeting any of the following criteria:

* Received prior combination chemotherapy and relapsed after treatment OR ineligible to receive such therapy
* Received prior salvage combination chemotherapy with or without high-dose chemotherapy followed by autologous hematopoietic stem cell rescue and relapsed after treatment OR ineligible to receive such therapy
* Lymphomatoid granulomatosis meeting any of the following criteria:

* Received prior single-agent or combination chemotherapy and relapsed after treatment OR ineligible to receive such therapy
* Has documentation of disease-associated symptoms, rapid disease progression, or other indications for treatment
* Acute lymphocytic leukemia meeting any of the following criteria:

* Received prior multi-agent combination chemotherapy administered in sequential induction, consolidation, and maintenance courses and relapsed during or after treatment OR ineligible to receive such therapy
* Received prior chemotherapy with or without radiotherapy followed by allogeneic hematopoietic stem cell transplantation (HSCT) and relapsed after treatment OR not a candidate for such therapy
* Received prior treatment with chemotherapy with or without radiotherapy followed by allogeneic HSCT and relapsed after treatment (or not a candidate for such therapy) AND demonstrates persistent cytogenetic, fluorescent in situ hybridization, or molecular (reverse transcriptase-polymerase chain reaction) evidence of the bcr-abl fusion gene despite 6 weeks of treatment with imatinib mesylate NOTE: \*Not eligible to receive standard available salvage regimens anticipated to result in durable remission
* No active CNS malignancy
* Not considered a candidate for allogeneic HSCT
* HLA-partially matched (≥ 2/6) related donor available

PATIENT CHARACTERISTICS:

* ECOG performance status 0-1
* Life expectancy \> 3 months
* Not pregnant
* Negative pregnancy test
* Fertile women must use effective contraception
* Bilirubin \< 1.5 times upper limit of normal (ULN)
* AST \< 3.0 times ULN
* Cardiac ejection fraction \> 35%
* Absolute neutrophil count \> 1,000/mm³ (without cytokines)
* Platelet count \> 50,000/mm³ (untransfused)
* No significant organ dysfunction
* No active uncontrolled infections
* No hypersensitivity reaction to rituximab that has precluded completion of a 4-week course of rituximab therapy
* No uncontrolled psychiatric illness or medical condition that would preclude tolerance of study treatment

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* Recovered from prior therapy for at least 7 days
* More than 30 days since prior cytotoxic chemotherapy
* At least 14 days since prior steroids
* At least 14 days since prior radiotherapy to non-target lesions
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

University of Medicine and Dentistry of New Jersey

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Roger Strair, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Rutgers Cancer Institute of New Jersey

Locations

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Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

New Brunswick, New Jersey, United States

Site Status

Countries

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United States

Other Identifiers

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P30CA072720

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CINJ-010406

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000540171

Identifier Type: -

Identifier Source: org_study_id