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Gene Therapy-Treated Stem Cells in Treating Patients Undergoing Stem Cell Transplant for Intermediate-Grade or High-Grade AIDS-Related Lymphoma
This study is ongoing, but not recruiting participants.
First Received: December 7, 2007   Last Updated: February 6, 2009   History of Changes
Sponsors and Collaborators: Beckman Research Institute
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00569985
  Purpose

RATIONALE: Placing a gene from HIV into a patient's stem cells may make the body build an immune response to kill cancer cells in patients with AIDS-related lymphoma.

PURPOSE: This clinical trial is studying the side effects and best dose of gene therapy in treating patients undergoing a stem cell transplant for intermediate-grade or high-grade AIDS-related lymphoma.


Condition Intervention
Lymphoma
Biological: filgrastim
Biological: gene therapy
Drug: carmustine
Drug: cyclophosphamide
Drug: etoposide
Procedure: autologous hematopoietic stem cell transplantation
Procedure: in vitro-treated peripheral blood stem cell transplantation

Study Type: Interventional
Study Design: Treatment
Official Title: A Pilot Study of Safety and Feasibility of Stem Cell Therapy for Aids Lymphoma Using Stem Cells Treated With a Lentivirus Vector-Encoding Multiple Anti-HIV RNAs

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Safety [ Designated as safety issue: Yes ]
  • Feasibility [ Designated as safety issue: No ]

Estimated Enrollment: 5
Study Start Date: June 2007
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • To determine the safety and feasibility of using lentivirus-transduced hematopoietic progenitor cells (HPCs) in the setting of autologous hematopoietic stem cell transplantation in patients with AIDS-related lymphoma.
  • To determine the quantity and duration of vector-marked peripheral blood cells and to characterize the duration and level of gene marking and expression of the anti-HIV RNAs in these transduced cells and the integration sites of vector sequences in circulating cells, if there is a clinical syndrome suggestive of a clonal expansion of hematopoietic cells.
  • To determine whether the design of the vector prevents vector mobilization and rescue by wild-type HIV-1.

OUTLINE: Patients undergo hematopoietic progenitor cell (HPC) mobilization with a combination of chemotherapy (using their prior antilymphoma regimen or cyclophosphamide) and filgrastim (G-CSF). Approximately 24 hours after completion of chemotherapy, patients receive G-CSF subcutaneously daily until the last apheresis is completed. A portion of the apheresis products are transduced with rHIV7-shI-TAR-CCR5RZ.

Patients receive high-dose conditioning regimen comprising carmustine IV over 4 hours on days -7 to -5, etoposide IV over 4 hours on day -4, and cyclophosphamide IV over 2 hours on day -2. Patients receive rHIV7-shI-TAR-CCR5RZ-transduced autologous HPCs IV over approximately 30 minutes on day 0 and standard non-transduced autologous HPCs IV over 30 minutes on day 1.

NOTE: Patients continue their anti-HIV regimen during antilymphoma chemotherapy, as prescribed by the physician managing their HIV infection; patients stop the anti-HIV regimen at the time of initiating HPC mobilization with G-CSF and resume it after the last apheresis is completed; patients also stop the anti-HIV regimen on day -7 (initiation of high-dose conditioning) and resume it on day 3 (post-transplantation).

After completion of study therapy, patients are followed periodically for up to 15 years.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • HIV seropositive at or before the time of lymphoma diagnosis

    • No detectible HIV-1 that has CXCR4-tropism
    • Must be on a multi-drug anti-HIV regimen (excluding zidovudine [AZT]) and have an HIV viral load < 50,000 copies/mL by RT-PCR at the time of study enrollment

      • Must agree to have anti-HIV regimen (HAART) temporarily stopped from the time filgrastim (G-CSF) is initiated for hematopoietic progenitor cell (HPC) mobilization until the mobilization is complete (approximately 7 days)
    • Must be on a prophylactic regimen for Pneumocystis carinii pneumonia, or agree to begin such treatment, if the CD4 count is ≤ 200/mm³
  • Meets 1 of the following criteria:

    • Biopsy proven intermediate- or high-grade non-Hodgkin lymphoma, meeting 1 of the following criteria:

      • In first complete remission with high-risk features as specified by the International Prognostic Index
      • In partial remission
      • Relapsed after initial complete remission
      • Failed induction therapy but responds to salvage therapy (i.e., chemosensitive disease)
    • Biopsy-proven Hodgkin lymphoma, meeting 1 of the following criteria:

      • In first or greater relapse after initial complete remission
      • In partial remission
      • Failed induction therapy but responds to salvage therapy (i.e., chemosensitive disease)
  • Patients with prior marrow involvement must demonstrate ≤ 10% involvement prior to stem cell collection
  • No abnormal cytogenetics not related to the lymphoma
  • No active CNS lymphoma

    • Patients with a history of positive cerebrospinal fluid cytology that has become negative with intrathecal chemotherapy are eligible
  • No history of HIV-associated encephalopathy
  • No other AIDS-related syndromes that are perceived to cause excessive risk for morbidity post-transplantation, as determined by the principal investigator

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 70-100%
  • SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN)
  • Serum bilirubin ≤ 2.5 times ULN
  • Patients who are hepatitis C virus antibody positive or hepatitis B virus surface antigen positive must be free of clinical evidence of cirrhosis as determined by the principal investigator in consultation with the Gastrointestinal Service
  • Amylase and lipase normal
  • Serum creatinine ≤ 2 times ULN
  • Creatinine clearance ≥ 60 mL/min
  • PT/PTT ≤ 2 times normal
  • Other laboratory value for CBC and chemistry panel ≤ 2 times ULN
  • FEV_1 or DLCO ≥ 50% predicted
  • LVEF ≥ 50% by 2-D ECHO or MUGA scan
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 1 year after transplantation
  • No symptomatic bacterial or fungal infection
  • No AIDS-related opportunistic infections within the past year for which treatment has been unsuccessful, as determined by the principal investigator
  • No active CMV retinitis or other active CMV-related organ dysfunction

    • Patients with a history of treated CMV infection are eligible
  • No relapse of Pneumocystis carinii pneumonia within the past year
  • No intractable, severe diarrhea, defined as > 1,500 cc diarrheal fluid per day, or diarrhea causing persistent severe electrolyte abnormalities or hypoalbuminemia
  • No history of myocardial infarction or congestive heart failure
  • No cardiomyopathy or dysrhythmia
  • No dementia of any kind
  • No seizures within the past 12 months
  • No history of grade III hemorrhagic cystitis due to prior cyclophosphamide chemotherapy
  • No other prior malignancy, except squamous cell carcinoma of the cervix or anus, superficial basal cell or squamous cell skin cancer, or other malignancy curatively treated ≥ 5 years ago
  • No psychosocial condition that would hinder study compliance and follow-up
  • No perceived inability to directly provide informed consent

    • Consent may not be obtained by means of a legal guardian
  • No medical or physical contraindication or other inability to undergo HPC collection

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00569985

Locations
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
Sponsors and Collaborators
Beckman Research Institute
Investigators
Study Chair: Amrita Y. Krishnan, MD Beckman Research Institute
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000577423, CHNMC-04047
Study First Received: December 7, 2007
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00569985     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
AIDS-related diffuse large cell lymphoma
AIDS-related diffuse mixed cell lymphoma
AIDS-related diffuse small cleaved cell lymphoma
AIDS-related immunoblastic large cell lymphoma
AIDS-related small noncleaved cell lymphoma
HIV-associated Hodgkin lymphoma
Treatment Experienced

Study placed in the following topic categories:
Immunologic Factors
Cyclophosphamide
Etoposide phosphate
Lymphoma, Large-cell, Immunoblastic
Lymphoma, Small Cleaved-cell, Diffuse
Lymphoma, B-Cell
Lymphoma, AIDS-Related
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, Large-cell
Alkylating Agents
Hodgkin Disease
Lymphoma
Etoposide
Lymphoma, AIDS-related
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Acquired Immunodeficiency Syndrome
Carmustine
Hodgkin's Disease
Small Non-cleaved Cell Lymphoma
Immunosuppressive Agents
Lymphatic Diseases
B-cell Lymphomas
HIV Infections
Primary Effusion Lymphoma
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Immunoproliferative Disorders
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Antineoplastic Agents
Physiological Effects of Drugs
Carmustine
Cyclophosphamide
Immunosuppressive Agents
Pharmacologic Actions
Lymphoma, B-Cell
Lymphatic Diseases
Neoplasms
Lymphoma, AIDS-Related
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Alkylating Agents
Lymphoma

ClinicalTrials.gov processed this record on July 06, 2009