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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
Sponsor: Beckman Research Institute
Collaborator: 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

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

ClinicalTrials.gov processed this record on November 27, 2009