Tumor-Infiltrating Lymphocytes in Treating Patients With Persistent or Recurrent B-Cell Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia or Multiple Myeloma After a Previous Donor Stem Cell Transplant

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2011 by National Institutes of Health Clinical Center (CC).
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00445666
First received: March 7, 2007
Last updated: September 29, 2011
Last verified: September 2011
  Purpose

RATIONALE: Biological therapies, such as cellular adoptive immunotherapy using tumor-infiltrating lymphocytes, may stimulate the immune system in different ways and stop cancer cells from growing.

PURPOSE: This phase I trial is studying the side effects and how well tumor-infiltrating lymphocytes work in treating patients with persistent or recurrent B-cell non-Hodgkin's lymphoma, Hodgkin's lymphoma, chronic lymphocytic leukemia, or multiple myeloma after a previous donor stem cell transplant.


Condition Intervention Phase
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Biological: graft-versus-tumor induction therapy
Biological: therapeutic tumor infiltrating lymphocytes
Genetic: cytogenetic analysis
Genetic: fluorescence in situ hybridization
Genetic: microarray analysis
Genetic: polymerase chain reaction
Other: flow cytometry
Other: immunoenzyme technique
Other: immunohistochemistry staining method
Other: immunologic technique
Other: laboratory biomarker analysis
Procedure: biopsy
Procedure: conventional surgery
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Adoptive Cell Therapy for B-Cell Malignancies After Allogeneic Hematopoietic Stem Cell Transplantation With Costimulated, Tumor-Derived Lymphocytes

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Feasibility (defined as 11 of 15 tumors yielding 1.0 × 10e7 tumor-derived lymphocytes/kg meeting defined release criteria) [ Designated as safety issue: No ]
  • Safety (defined as having no greater risk of developing acute graft-versus-host disease by day 28 as with standard therapy with unmanipulated donor lymphocyte infusion) [ Designated as safety issue: Yes ]

Estimated Enrollment: 36
Study Start Date: August 2007
Detailed Description:

OBJECTIVES:

Primary

  • Determine the feasibility of administering ex vivo costimulated, expanded, clinically relevant numbers of tumor-derived lymphocytes (TDL) from surgically resected tumor (TDL) and tumor-involved bone marrow (marrow-TDL) in patients with persistent or recurrent B-cell lymphoid malignancies after prior allogeneic hematopoietic stem cell transplantation (alloHSCT).
  • Determine the safety of TDL, in terms of the incidence of infusion-related toxicities, hyperacute graft-versus-host disease (GVHD), or acute or chronic GVHD, in these patients.

Secondary

  • Determine antitumor response in patients treated with TDL.
  • Investigate methods of characterizing residual tumor after alloHSCT by evaluating patient tumor and bone marrow tissue samples for tumor viability and inflammatory infiltrate; assessing residual tumor cells for antigen specificity and gene expression; and assaying TDL for tumor reactivity and specificity.
  • Investigate methods of characterizing the immune phenotypic and functional characteristics of patient TDL and tumor-selected TDL and compare the in vitro antitumor efficacy of these two cell products.
  • Identify recombinant, graft-versus-tumor (GVT) antigens in tumor samples before and after administration of TDL to better understand the mechanisms and effectors of GVT response in these patients.
  • Investigate methods of characterizing tumor infiltrate in these patients by evaluating tumor and bone marrow tissue samples for viability and inflammatory infiltrate; assessing residual tumor cells for enhanced antigen specificity and gene expression; and assaying TDL for tumor reactivity and specificity.
  • Investigate the effect of immune depletion in these patients on the availability of homeostatic cytokines and the requirement for exogenous cytokine support of in-vivo survival and expansion of adoptively transferred cells.

OUTLINE: This is a pilot study.

Patients undergo apheresis to collect peripheral blood mononuclear cells (PBMCs). Patients then undergo surgical resection of accessible tumor and/or bone marrow is collected. Tumor-infiltrating T lymphocytes (TILs) are isolated from tumor tissue, costimulated with PBMCs, and expanded ex vivo to generate tumor-derived lymphocytes (TDLs). Beginning at least 24 days after surgery and within 7 days after tumor assessment, patients receive an infusion of TDL IV in the absence of disease progression or unacceptable toxicity.

Patients undergo blood, bone marrow, and tissue collection periodically during study for correlative studies, including the following: phenotypic and functional characterization of residual tumor and TDL by immunohistochemistry and fluorescent in situ hybridization; identification of prognostic markers of clinical outcome (i.e., HLA-A, -B, and -C; HLA-DR, Fas ligand, CD80, and CD86) by flow cytometry; in vitro assessment of tumor-reactive, selectively expanded T-cell clones by gene expression profiling; and evaluation of immune response by tumor-specific cytotoxicity assays (immunoenzyme techniques) and DNA sequencing for recombinant graft-versus-tumor antigens. Chimerism is assessed with a polymerase chain reaction-based assay and cytogenetics.

After completion of study therapy, patients are followed periodically for at least 5 years.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed B-cell non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma chronic lymphocytic leukemia, non T-cell acute lymphoblastic leukemia (B-cell ALL), or multiple myeloma

    • Persistent or recurrent disease after last systemic treatment
  • Underwent prior allogeneic hematopoietic stem cell transplantation (alloHSCT) and failed to respond to the following after a minimum of 4 weeks:

    • Withdrawal of immunosuppressive therapy trial, including trials that were discontinued due to development of graft-versus-host disease (GVHD)
    • Administration of ≥ 1 donor lymphocyte infusion (DLI) with a minimum T-cell dose of 1 x 10^7 CD3-positive cells/kg*
    • Evidence of stable or increasing donor engraftment over the past 3 months (≥ 50% donor chimerism in the bone marrow, whole blood, and/or circulating CD3+ lymphoid pool) NOTE: *Patients who have relapsed after prior alternative donor alloHSCT (e.g., haploidentical, matched unrelated, umbilical cord blood) without failing DLI are eligible
  • Presence of bone marrow involvement with tumor and/or at least 1 lymph node with ≥ 1.5 cm³ of accessible tumor available for resection with minimal surgical morbidity and hospitalization
  • Presence of at least 1 other site of disease that permits monitoring for response to therapy
  • Minimal to no clinical evidence (grade 0-1) of acute GVHD or limited-stage chronic GVHD while off systemic immunosuppressive therapy for ≥ 4 weeks
  • No untreated leptomeningeal involvement with malignancy

    • Lumbar puncture required for patients with aggressive NHL, history of leptomeningeal disease, or signs or symptoms suggestive of leptomeningeal involvement

PATIENT CHARACTERISTICS:

  • ECOG performance status (PS) 0-2 (Karnofsky PS 60-100%)
  • Life expectancy > 3 months
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 1 year after completion of study therapy
  • Absolute neutrophil count ≥ 500/mm³ (or < 500/mm³ attributed to tumor )
  • Platelet count ≥ 20,000/mm³ (without transfusion) (> 50,000/mm³, if transfusion-dependent)
  • Creatinine < 2.5 mg/dL
  • Creatinine clearance > 40 mL/min
  • Bilirubin ≤ 2.5 mg/dL (≤ 5 mg/dL if attributable to liver involvement by malignancy*)
  • AST and ALT < 2.5 times upper limit of normal (ULN) (≤ 5 times ULN if attributable to liver involvement by malignancy*)
  • PT and PTT normal (or demonstrably not related to coagulopathy)

    • No PT > 6 seconds attributable to hepatic failure (in the absence of vitamin K deficiency, pharmacologic anticoagulation, or identifiable clotting abnormality)
  • LVEF ≥ 45% by MUGA or 2-dimensional echocardiogram
  • DLCO ≥ 50% of predicted (corrected for hemoglobin)
  • No active infection that is not responding to antimicrobial therapy
  • No active psychiatric illness that would preclude compliance with transplantation protocol or giving informed consent NOTE: *Provided the patient has no evidence of impending hepatic failure (i.e., encephalopathy or PT > 2 times ULN)

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 2 weeks since prior cytotoxic therapy or immunotherapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00445666

Locations
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
Investigators
Principal Investigator: Michael R. Bishop, MD National Cancer Institute (NCI)
  More Information

Additional Information:
No publications provided by National Institutes of Health Clinical Center (CC)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00445666     History of Changes
Other Study ID Numbers: 070064, CDR0000532130, NCI-07-C-0064
Study First Received: March 7, 2007
Last Updated: September 29, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
recurrent small lymphocytic lymphoma
splenic marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
recurrent mantle cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult Burkitt lymphoma
B-cell chronic lymphocytic leukemia
refractory chronic lymphocytic leukemia
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent marginal zone lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
refractory multiple myeloma
recurrent adult Hodgkin lymphoma
recurrent adult acute lymphoblastic leukemia

Additional relevant MeSH terms:
Neoplasms
Hodgkin Disease
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Lymphoma, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoma, Non-Hodgkin

ClinicalTrials.gov processed this record on July 31, 2014