Clinical trial NCT00176475: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: 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
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-09-15
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Toxicity as assessed by NCI CTCAE v3.0
timeFrame: 4 years
Secondary outcomes:
measure: Efficacy
timeFrame: 4 years
Other outcomes:
Locations:
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
state: New Jersey
Study officials:
affiliation: Rutgers Cancer Institute of New Jersey
name: Roger Strair, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: