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

Lymphoma Clinical Trial

Official title:

A Pilot Study of Irradiated HLA-Partially Matched Allogeneic Related Donor Lymphocytes in Conjunction With Rituximab for Selected Patients With CD20 + Malignancies

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00176475
• Other study ID #: CDR0000540171
• Secondary ID: P30CA072720CINJ-
• Status: Terminated
• Phase: Phase 1
• First received: September 12, 2005
• Last updated: September 13, 2013
• Start date: January 2005
• Est. completion date: February 2008

Study information

• Verified date: September 2013
• Source: Rutgers, The State University of New Jersey
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: February 2008
• Est. primary completion date: February 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Lymphoma
• Lymphoproliferative Disorders
• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Neoplasms, Plasma Cell
• Plasmacytoma

Intervention

Biological:
• 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).
• 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

Locations

Country	Name	City	State
United States	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
University of Medicine and Dentistry of New Jersey	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity as assessed by NCI CTCAE v3.0		4 years	Yes
Secondary	Efficacy		4 years	No