Irradiated Donor Lymphocyte Infusion in Treating Patients With Relapsed or Refractory Hematologic Cancer or Solid Tumor

Cancer Clinical Trial

Official title:

A Pilot Study of Irradiated HLA-Partially Matched Allogeneic Related Donor Lymphocytes for Patients With Selected Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00161187
• Other study ID #: 010101
• Secondary ID: P30CA07272002200
• Status: Completed
• Phase: Phase 1
• First received: September 8, 2005
• Last updated: November 5, 2015
• Start date: May 2001
• Est. completion date: October 2011

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.

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: October 2011
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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-a, 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

Study Design

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

Related Conditions & MeSH terms

• Cancer

Intervention

Biological:
• therapeutic allogeneic lymphocytes
The total CD3+ cell dose target is 1.8 x 108 CD3+ cells/kg +/- 1.0 x 108 CD3+ cells/kg. Up to 6 cycles.

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		10 years	Yes
Secondary	Response		10 years	No
Secondary	Presence of disease or antigen-specific lymphocytes		10 years	No