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

Primary Purpose

Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
rituximab
therapeutic allogeneic lymphocytes
Sponsored by
University of Medicine and Dentistry of New Jersey
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically confirmed lymphoproliferative disease CD20-positive disease Bidimensionally measurable disease OR abnormal cells detected in blood Resistant or refractory to standard therapies and/or unlikely to benefit from additional standard therapies* AND meets 1 of the following criteria: Disease with anticipated response rate < 20% after treatment with rituximab alone, including any of the following: Diffuse large cell lymphoma B-cell lymphoblastic lymphoma Burkitt's lymphoma Acute lymphocytic leukemia Relapsed or progressive disease after prior treatment with rituximab, including any of the following: Hodgkin's lymphoma Hairy cell leukemia Chronic lymphocytic leukemia/small lymphocytic lymphoma meeting any of the following criteria: Received prior fludarabine phosphate-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 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

Sites / Locations

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Therapeutic allogeneic lymphocytes with rituximab

Arm Description

Outcomes

Primary Outcome Measures

Toxicity as assessed by NCI CTCAE v3.0

Secondary Outcome Measures

Efficacy

Full Information

First Posted
September 12, 2005
Last Updated
September 13, 2013
Sponsor
University of Medicine and Dentistry of New Jersey
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00176475
Brief Title
Irradiated Donor Lymphocytes and Rituximab in Treating Patients With Relapsed or Refractory Lymphoproliferative Disease
Official Title
A Pilot Study of Irradiated HLA-Partially Matched Allogeneic Related Donor Lymphocytes in Conjunction With Rituximab for Selected Patients With CD20 + Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
September 2013
Overall Recruitment Status
Terminated
Why Stopped
slow accrual
Study Start Date
January 2005 (undefined)
Primary Completion Date
February 2008 (Actual)
Study Completion Date
February 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Medicine and Dentistry of New Jersey
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Therapeutic allogeneic lymphocytes with rituximab
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
rituximab
Intervention Description
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
Intervention Name(s)
therapeutic allogeneic lymphocytes
Intervention Description
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
Primary Outcome Measure Information:
Title
Toxicity as assessed by NCI CTCAE v3.0
Time Frame
4 years
Secondary Outcome Measure Information:
Title
Efficacy
Time Frame
4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed lymphoproliferative disease CD20-positive disease Bidimensionally measurable disease OR abnormal cells detected in blood Resistant or refractory to standard therapies and/or unlikely to benefit from additional standard therapies* AND meets 1 of the following criteria: Disease with anticipated response rate < 20% after treatment with rituximab alone, including any of the following: Diffuse large cell lymphoma B-cell lymphoblastic lymphoma Burkitt's lymphoma Acute lymphocytic leukemia Relapsed or progressive disease after prior treatment with rituximab, including any of the following: Hodgkin's lymphoma Hairy cell leukemia Chronic lymphocytic leukemia/small lymphocytic lymphoma meeting any of the following criteria: Received prior fludarabine phosphate-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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roger Strair, MD, PhD
Organizational Affiliation
Rutgers Cancer Institute of New Jersey
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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