Clinical trial NCT00161187: Irradiated Donor Lymphocyte Infusion in Treating Patients With Relapsed or Refractory Hematologic Cancer or Solid Tumor
Official title: A Pilot Study of Irradiated HLA-Partially Matched Allogeneic Related Donor Lymphocytes for Patients With Selected Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer
Keywords: refractory chronic lymphocytic leukemia
recurrent small lymphocytic lymphoma
prolymphocytic leukemia
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
recurrent marginal zone lymphoma
splenic marginal zone lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
recurrent mantle cell lymphoma
childhood diffuse large cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult Burkitt lymphoma
recurrent adult grade III lymphomatoid granulomatosis
recurrent childhood grade III lymphomatoid granulomatosis
adult nasal type extranodal NK/T-cell lymphoma
childhood nasal type extranodal NK/T-cell lymphoma
recurrent mycosis fungoides/Sezary syndrome
anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
recurrent adult T-cell leukemia/lymphoma
recurrent adult Hodgkin lymphoma
recurrent/refractory childhood Hodgkin lymphoma
recurrent adult acute myeloid leukemia
recurrent childhood acute myeloid leukemia
childhood chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
recurrent renal cell cancer
stage IV renal cell cancer
recurrent bladder cancer
stage IV bladder cancer
recurrent prostate cancer
stage IV prostate cancer
recurrent malignant testicular germ cell tumor
stage III malignant testicular germ cell tumor
recurrent gastric cancer
stage IV gastric cancer
recurrent pancreatic cancer
stage IV pancreatic cancer
localized unresectable adult primary liver cancer
recurrent adult primary liver cancer
recurrent childhood liver cancer
recurrent colon cancer
stage IV colon cancer
recurrent rectal cancer
stage IV rectal cancer
recurrent breast cancer
stage IV breast cancer
extensive stage small cell lung cancer
recurrent non-small cell lung cancer
recurrent small cell lung cancer
stage IV non-small cell lung cancer
recurrent ovarian epithelial cancer
recurrent cervical cancer
recurrent adult soft tissue sarcoma
stage IV adult soft tissue sarcoma
chondrosarcoma
recurrent osteosarcoma
previously treated childhood rhabdomyosarcoma
recurrent childhood rhabdomyosarcoma
ovarian sarcoma
recurrent uterine sarcoma
stage IV uterine sarcoma
stage I small lymphocytic lymphoma
contiguous stage II small lymphocytic lymphoma
noncontiguous stage II small lymphocytic lymphoma
stage III small lymphocytic lymphoma
stage IV small lymphocytic lymphoma
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
recurrent childhood large cell lymphoma
stage I childhood large cell lymphoma
stage II childhood large cell lymphoma
stage III childhood large cell lymphoma
stage IV childhood large cell lymphoma
adult primary hepatocellular carcinoma
advanced adult primary liver cancer
ovarian stromal cancer
stage IA cervical cancer
stage IB cervical cancer
stage IIA cervical cancer
stage IIB cervical cancer
stage III cervical cancer
stage IVA cervical cancer
stage IVB cervical cancer
recurrent adult acute lymphoblastic leukemia
untreated adult acute lymphoblastic leukemia
recurrent childhood acute lymphoblastic leukemia
untreated childhood acute lymphoblastic leukemia
recurrent endometrial carcinoma
stage I endometrial carcinoma
stage II endometrial carcinoma
stage III endometrial carcinoma
stage IV endometrial carcinoma
childhood hepatocellular carcinoma
stage III childhood liver cancer
stage IV childhood liver cancer
previously untreated childhood rhabdomyosarcoma
metastatic childhood soft tissue sarcoma
localized Ewing sarcoma/peripheral primitive neuroectodermal tumor
metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor
recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
contiguous stage II grade 1 follicular lymphoma
contiguous stage II grade 2 follicular lymphoma
contiguous stage II grade 3 follicular lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
stage I grade 1 follicular lymphoma
stage I grade 2 follicular lymphoma
stage I grade 3 follicular 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
contiguous stage II marginal zone lymphoma
noncontiguous stage II marginal zone lymphoma
stage I marginal zone lymphoma
stage III marginal zone lymphoma
stage IV marginal zone lymphoma
localized osteosarcoma
metastatic osteosarcoma
stage I ovarian epithelial cancer
stage II ovarian epithelial cancer
stage III ovarian epithelial cancer
stage IV ovarian epithelial cancer
recurrent ovarian germ cell tumor
stage I ovarian germ cell tumor
stage II ovarian germ cell tumor
stage III ovarian germ cell tumor
stage IV ovarian germ cell tumor
limited stage small cell lung cancer
refractory multiple myeloma
stage II malignant testicular germ cell tumor
stage I adult soft tissue sarcoma
stage II adult soft tissue sarcoma
stage III adult soft tissue sarcoma
stage I bladder cancer
stage II bladder cancer
stage III bladder cancer
male breast cancer
stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage I colon cancer
stage II colon cancer
stage III colon cancer
stage I gastric cancer
stage II gastric cancer
stage III gastric cancer
stage I non-small cell lung cancer
stage II non-small cell lung cancer
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage I pancreatic cancer
stage II pancreatic cancer
stage III pancreatic cancer
stage I prostate cancer
stage II prostate cancer
stage III prostate cancer
stage I rectal cancer
stage II rectal cancer
stage III rectal cancer
stage I renal cell cancer
stage II renal cell cancer
stage III renal cell cancer
stage I uterine sarcoma
stage II uterine sarcoma
stage III uterine sarcoma
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
contiguous stage II mantle cell lymphoma
noncontiguous stage II mantle cell lymphoma
stage I mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
Waldenstrom macroglobulinemia
contiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
stage I adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma
contiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult Burkitt lymphoma
stage I adult Burkitt lymphoma
stage III adult Burkitt lymphoma
stage IV adult Burkitt lymphoma
stage I mycosis fungoides/Sezary syndrome
stage II mycosis fungoides/Sezary syndrome
stage III mycosis fungoides/Sezary syndrome
stage IV mycosis fungoides/Sezary syndrome
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
untreated adult acute myeloid leukemia
untreated childhood acute myeloid leukemia and other myeloid malignancies
de novo myelodysplastic syndromes
secondary myelodysplastic syndromes
previously treated myelodysplastic syndromes
nonmetastatic childhood soft tissue sarcoma
recurrent childhood soft tissue sarcoma
stage I childhood Hodgkin lymphoma
stage II childhood Hodgkin lymphoma
stage III childhood Hodgkin lymphoma
stage IV childhood Hodgkin lymphoma
stage I adult Hodgkin lymphoma
stage II adult Hodgkin lymphoma
stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
recurrent childhood small noncleaved cell lymphoma
stage I childhood small noncleaved cell lymphoma
stage II childhood small noncleaved cell lymphoma
stage III childhood small noncleaved cell lymphoma
stage IV childhood small noncleaved cell lymphoma
Burkitt lymphoma
stage I adult T-cell leukemia/lymphoma
stage II adult T-cell leukemia/lymphoma
stage III adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma
stage I malignant testicular germ cell tumor
childhood myelodysplastic syndromes
childhood renal cell carcinoma
stage IA melanoma
stage IB melanoma
stage IIA melanoma
stage IIB melanoma
stage IIC melanoma
stage IIIA melanoma
stage IIIB melanoma
stage IIIC melanoma
stage IV melanoma
recurrent melanoma
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-09-12
Enrollment: 37
Sex: ALL
Standard ages: CHILD
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.

PURPOSE: This pilot study is looking at the side effects and how well irradiated donor lymphocyte infusion works in treating patients with relapsed or refractory hematologic cancer or solid tumor.

Detailed description: OBJECTIVES:

* Determine the toxicity of irradiated allogeneic donor lymphocyte infusion in patients with relapsed or refractory hematological cancer or solid tumor.
* Determine the response in patients treated with this regimen.
* Determine the presence of disease or antigen-specific lymphocytes in patients treated with this regimen.

OUTLINE: This is a pilot, open-label, controlled study.

Patients undergo irradiated allogeneic donor lymphocyte infusion over 1 hour on day 1. Treatment repeats every 8-16 weeks for up to 6 infusions in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically and analyzed for lymphocytotoxicity directed towards patients' cells (normal and malignant cells) and for disease or antigen-specific cells. Samples are also analyzed for survival of donor lymphocytes by chimerism studies.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed diagnosis of 1 of the following:

  * Hematologic cancer, including any of the following:

    * Chronic lymphocytic leukemia or small lymphocytic lymphoma meeting any of the following criteria:

      * Relapsed within 1 year after prior fludarabine phosphate-containing regimens OR not a candidate 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)
      * Has documentation of disease-associated symptoms, rapid progression of disease, or other indications for treatment
    * B- or T-cell prolymphocytic leukemia meeting any of the following criteria:

      * Relapsed within 1 year after prior fludarabine phosphate- or alkylating agent-containing regimens OR not a candidate to receive such therapy due to comorbidities or allergies
      * Relapsed within 1 year after prior anti-CD20 monoclonal antibody therapy OR ineligible to receive such therapy (for patients with CD20-positive disease)
      * 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:

      * Relapsed within 1 year after prior fludarabine phosphate- or alkylating agent-containing regimens or radioconjugated anti-CD20 monoclonal antibody OR not a candidate to receive such therapy due to comorbidities or allergies
      * Relapsed within 1 year after prior anti-CD20 monoclonal antibody therapy OR ineligible to receive such therapy (for patients with CD20-positive disease)
      * Has documentation of disease-associated symptoms, rapid progression of disease, or other indications for treatment
    * Multiple myeloma meeting any of the following criteria:

      * Relapsed after prior alkylating agents, thalidomide, corticosteroids, or bortezomib OR not a candidate to receive such therapy due to comorbidities or allergies
      * Relapsed after prior high-dose chemotherapy followed by autologous hematopoietic stem cell rescue OR not a candidate to receive such therapy
    * Mantle cell lymphoma that has relapsed after prior combination chemotherapy or anti-CD20 monoclonal antibody OR not a candidate to receive such therapy
    * Diffuse large B-cell lymphoma meeting any of the following criteria:

      * Relapsed after prior salvage combination chemotherapy with or without high-dose chemotherapy followed by autologous hematopoietic stem cell rescue OR not a candidate to receive such therapy
      * Received prior radiolabeled anti-CD20 monoclonal antibody OR ineligible to receive such therapy (for patients with transformed large cell lymphoma)
    * Burkitt's lymphoma

      * Relapsed after prior salvage combination chemotherapy with or without high-dose chemotherapy followed by autologous hematopoietic stem cell rescue OR not a candidate for such therapy
    * Lymphomatoid granulomatosis or mature T-cell or NK-cell neoplasms meeting any of the following criteria:

      * Relapsed after prior single agent or combination chemotherapy OR not a candidate to receive such therapy
      * Has documentation of disease-associated symptoms, rapid progression of disease, or other indications for treatment
    * Mycosis fungoides or Sezary syndrome

      * Relapsed after prior combination chemotherapy, interferon-α, denileukin diftitox, or extracorporeal photophoresis OR not a candidate to receive such therapy
    * Anaplastic large cell lymphoma, peripheral T-cell lymphoma unspecified, or angioimmunoblastic T-cell lymphoma meeting the following criteria:

      * Relapsed after prior salvage combination chemotherapy with or without high-dose chemotherapy followed by autologous hematopoietic stem cell rescue OR not a candidate to receive such therapy
    * Hepatosplenic T-cell lymphoma or adult T-cell leukemia/lymphoma

      * Relapsed after prior salvage combination chemotherapy OR not a candidate to receive such therapy
    * Hodgkin's lymphoma

      * Relapsed after prior salvage combination chemotherapy with or without high-dose chemotherapy followed by autologous hematopoietic stem cell rescue OR not a candidate to receive such therapy
    * Acute lymphocytic leukemia meeting any of the following criteria:

      * Relapsed during or after prior multi-agent combination chemotherapy administered in sequential induction, consolidation, and maintenance courses OR not a candidate to receive such therapy
      * Relapsed after prior salvage combination chemotherapy with or without high-dose chemotherapy followed by autologous hematopoietic stem cell rescue OR not a candidate to receive such therapy
      * Relapsed after prior chemotherapy with or without radiotherapy followed by allogeneic hematopoietic stem cell transplant (or ineligible for such therapy) AND demonstrates persistent cytogenetic, fluorescent in situ hybridization (FISH), or molecular (reverse transcriptase-polymerase chain reaction) evidence of bcr-abl fusion gene despite 6 weeks of treatment with imatinib mesylate
    * Acute myelogenous leukemia or myelodysplasia meeting any of the following criteria:

      * Relapsed or refractory disease after prior induction chemotherapy (anthracycline and cytarabine, topotecan hydrochloride and cytarabine, or comparable regimen) OR not a candidate to receive such therapy
      * Not a candidate for chemotherapy with or without radiotherapy followed by allogeneic or autologous hematopoietic stem cell transplant
      * Patients with acute promyelomonocytic leukemia must have received prior tretinoin and arsenic trioxide
    * Chronic myelogenous leukemia meeting any of the following criteria:

      * Relapsed or refractory disease after prior imatinib mesylate
      * Not a candidate for chemotherapy with or without radiotherapy followed by allogeneic hematopoietic stem cell transplant
      * Chronic phase disease allowed if there is FISH or cytogenetic evidence of increasing disease
  * Solid tumor, including any of the following:

    * Renal cell carcinoma

      * Metastatic relapsed or refractory disease after prior high-dose aldesleukin OR ineligible to receive such therapy due to comorbidities OR did not consent to treatment
    * Bladder cancer or gastric cancer

      * Metastatic relapsed or refractory disease after prior combination therapy OR not a candidate to receive such therapy
    * Prostate cancer

      * Metastatic relapsed or refractory disease after prior hormonal therapy OR not a candidate to receive such therapy
    * Testicular cancer

      * Metastatic relapsed or refractory disease after prior standard induction or salvage chemotherapy or high-dose chemotherapy with autologous hematopoietic stem cell rescue OR not a candidate to receive such therapy
    * Pancreatic cancer

      * Metastatic relapsed or refractory disease after prior gemcitabine hydrochloride-based therapy OR not a candidate to receive such therapy
    * Hepatocellular carcinoma

      * Unresectable or metastatic disease
    * Colorectal carcinoma

      * Metastatic relapsed or refractory disease after prior combination therapy, including fluorouracil with or without leucovorin calcium, oxaliplatin, or irinotecan hydrochloride OR not a candidate to receive such therapy
    * Breast cancer meeting any of the following criteria:

      * Metastatic relapsed or refractory disease after prior first- or second-line standard combination chemotherapy OR not a candidate to receive such therapy
      * Received prior trastuzumab (Herceptin®) and sequential hormonal therapy OR not a candidate to receive such therapy as indicated by the biological characteristics of the cancer
    * Lung cancer (non-small cell or small cell lung cancer), ovarian cancer, endometrial cancer, or cervical cancer

      * Metastatic relapsed or refractory disease after prior first- or second-line combination chemotherapy OR not a candidate to receive such therapy
    * Malignant melanoma

      * Metastatic relapsed or refractory disease after prior immunotherapy or combination chemotherapy OR not a candidate to receive such therapy
    * Sarcoma meeting any of the following criteria:

      * Metastatic relapsed or refractory disease after prior first- or second-line combination chemotherapy OR not a candidate to receive such therapy
      * Not a candidate for resection
      * Patients with gastrointestinal stromal tumors must have received prior imatinib mesylate
* Measurable disease
* Must have received prior available standard therapy for specific disease OR not a candidate for this treatment
* No CNS malignancy
* HLA-partially matched (≥ 2/6 HLA antigen \[A, B, DR\]) related donor (above 18 years of age) available

PATIENT CHARACTERISTICS:

* ECOG performance status 0-1
* Life expectancy \> 3 months
* Bilirubin \< 1.5 times upper limit of normal (ULN)
* AST \< 3.0 times ULN
* LVEF \> 35%
* No active infections
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No uncontrolled medical or psychiatric illness that would preclude study compliance, in the opinion of the investigator

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics

Primary outcomes:
measure: Toxicity
timeFrame: 10 years
Secondary outcomes:
measure: Response
timeFrame: 10 years
measure: Presence of disease or antigen-specific lymphocytes
timeFrame: 10 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: