Genetically Modified Peripheral Blood Stem Cell Transplant in Treating Patients With HIV-Associated Non-Hodgkin or Hodgkin Lymphoma

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified June 2014 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01769911
First received: January 15, 2013
Last updated: June 23, 2014
Last verified: June 2014
  Purpose

This clinical trial studies genetically modified peripheral blood stem cell transplant in treating patients with HIV-associated non-Hodgkin or Hodgkin lymphoma. Giving chemotherapy before a peripheral stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy or radiation therapy is then given to prepare the bone marrow for the stem cell transplant. Laboratory-treated stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and radiation therapy


Condition Intervention
Adult Nasal Type Extranodal NK/T-cell Lymphoma
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 Lymphoblastic Lymphoma
AIDS-related Peripheral/Systemic Lymphoma
AIDS-related Small Noncleaved Cell Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Cutaneous B-cell Non-Hodgkin Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Hepatosplenic T-cell Lymphoma
HIV-associated Hodgkin Lymphoma
Intraocular Lymphoma
Nodal Marginal Zone B-cell Lymphoma
Noncutaneous Extranodal Lymphoma
Peripheral T-cell Lymphoma
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Small Lymphocytic Lymphoma
Refractory Hairy Cell Leukemia
Small Intestine Lymphoma
Splenic Marginal Zone Lymphoma
Stage I AIDS-related Lymphoma
Stage II AIDS-related Lymphoma
Stage III AIDS-related Lymphoma
Stage IV AIDS-related Lymphoma
T-cell Large Granular Lymphocyte Leukemia
Testicular Lymphoma
Waldenström Macroglobulinemia
Drug: carmustine
Drug: cytarabine
Drug: melphalan
Drug: etoposide
Drug: O6-benzylguanine
Procedure: autologous hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Other: laboratory biomarker analysis

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: AUTOLOGOUS TRANSPLANTATION AND STEM CELL BASED-GENE THERAPY FOR THE TREATMENT OF HIV-ASSOCIATED LYMPHOMA

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Safety of infusion of gene-modified cells, measured by grade 3 or greater toxicities related to infusion of gene-modified cells using the Common Toxicity Criteria version 4.0(CTCv.4) [ Time Frame: Up to day 180 ] [ Designated as safety issue: Yes ]
  • Safety of O6BG/BCNU in vivo selection, defined as less than 25% of patients developing grade 3 or greater non-hematopoietic toxicity or grade 4 CTCv.4 hematopoietic toxicity [ Time Frame: Up to day 180 ] [ Designated as safety issue: Yes ]
  • Safety of structured treatment interruption defined as no decline in CD4 count by more than 25%, no HIV RNA more than 10,000 copies/mL; and no elevation of immune activation markers [ Time Frame: During the 12 weeks without HAART ] [ Designated as safety issue: Yes ]
  • Efficacy of gene transduction, defined as collection of more than 4.5 x 10^6 CD34+ cells/kg cells for genetic modification and evidence of gene-marked cells before HSC infusion [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Efficacy of infusion of gene-modified cells, defined as engraftment of at least1% gene-modified cells [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
  • Efficacy of O6BG/BCNU in vivo selection, defined as selection of gene-modified cells to a level at least 10% of peripheral blood cells [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 13
Study Start Date: October 2014
Estimated Primary Completion Date: February 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (gene modified peripheral blood cell transplant)

CONDITIONING: Patients receive carmustine IV over 3 hours on day -7, cytarabine IV over 2 hours BID and etoposide IV over 2 hours BID on days -6 to -3, and melphalan IV over 30 minutes on day -2.

TRANSPLANTATION: Patients receive an autologous PBSC infusion and/or infusion of autologous transduced hematopoietic cells on day 0.

Beginning 28-120 days later, patients eligible for in vivo selection after detection of gene-marked cells receive O6-benzylguanine IV over 1 hour and carmustine IV over 3 hours on days 14, 28, and then monthly until completion of therapy. Patients achieving > 10% gene marking and CD4 count of >= 500 cells/uL receive up to 2 courses of structured treatment interruption without undergoing in vivo selection.

Drug: carmustine
Given IV
Other Names:
  • BCNU
  • BiCNU
  • bis-chloronitrosourea
Drug: cytarabine
Given IV
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: melphalan
Given IV
Other Names:
  • Alkeran
  • CB-3025
  • L-PAM
  • L-phenylalanine mustard
  • L-Sarcolysin
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: O6-benzylguanine
Given IV
Other Name: BG
Procedure: autologous hematopoietic stem cell transplantation
Undergo transduced and/or non-transduced transplant
Procedure: peripheral blood stem cell transplantation
Undergo transduced and/or non-transduced transplant
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the safety and feasibility of infusing gene-modified, human immunodeficiency virus (HIV)-protected hematopoietic stem cells (HSC) after high-dose chemotherapy for treatment of acquired immunodeficiency syndrome (AIDS)-related lymphoma.

II. To determine the dose of carmustine (BCNU) in combination with O^6-benzylguanine (O6BG) that results in selection in vivo of gene-modified HIV-resistant cells.

III. To estimate the effect of HIV infection on the presence of HIV-resistant blood cells as measured by genetic marking for vector sequences before and after antiviral treatment interruption.

SECONDARY OBJECTIVES:

I. Evaluate the molecular and clonal composition of gene-modified cells after hematopoietic cell transplant (HCT).

II. Evaluate the molecular and clonal composition of gene-modified cells after O6BG/BCNU.

III. Determine the correlation of the level of O6-methylguanine- methyltransferase (MGMT) (P140K) marking with toxicity and response.

IV. Characterize the toxicity associated with in vivo selection. V. Determine the efficacy of the procedure for treatment of lymphoma: defined as time to disease progression, progression-free survival, treatment-related mortality, time to neutrophil and platelet recovery, and incidence of infections.

TERTIARY OBJECTIVES:

I. Effect of procedure on the latent HIV reservoir. II. Effect of procedure on HIV-specific immune reconstitution.

OUTLINE:

CONDITIONING: Patients receive carmustine intravenously (IV) over 3 hours on day -7, cytarabine IV over 2 hours twice daily (BID) and etoposide IV over 2 hours BID on days -6 to -3, and melphalan IV over 30 minutes on day -2.

TRANSPLANTATION: Patients receive an autologous PBSC infusion and/or infusion of autologous transduced hematopoietic cells on day 0.

Beginning 28-120 days later, patients eligible for in vivo selection after detection of gene-marked cells receive O6-benzylguanine IV over 1 hour and carmustine IV over 3 hours on days 14, 28, and then monthly until completion of therapy. Patients achieving > 10% gene marking and CD4 count of >= 500 cells/uL receive up to 2 courses of structured treatment interruption without undergoing in vivo selection.

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

  Eligibility

Ages Eligible for Study:   18 Years to 66 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV seropositive
  • Antiretroviral treatment for at least one month, defined as a multi-drug regimen (excluding azacitidine [AZT])
  • HIV plasma viral load has decreased by 1.5 logs or viral load < 5000 copies/ml
  • Non-Hodgkin or Hodgkin lymphoma without active central nervous system (CNS) involvement associated with poor prognosis with medical therapy alone or for which autologous peripheral blood stem cell (PBSC) transplant is indicated:

    • Hodgkin's lymphoma beyond first remission; first partial remission; induction failure with subsequent response to salvage therapy
    • Non-Hodgkin's Lymphoma beyond first remission: first partial remission; induction failure with subsequent response to salvage therapy
    • Chemotherapy responsive disease
  • Karnofsky performance score >= 70%
  • Subjects must agree to use effective contraception from enrollment through completion of the study
  • Female subjects: if of child bearing potential, must have negative serum or urine pregnancy test within 7 days of treatment
  • Subjects must be on a prophylactic regimen for Pneumocystis carinii pneumonia, or agree to begin such treatment, if the cluster of differentiation (CD)4 counts are =< 200
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Serum creatinine > 2 times upper limit of normal
  • Serum bilirubin greater than 3 times the upper limits of normal, unless determined to be a result of the primary hematologic malignancy or attributed to Gilbert's syndrome
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 times the upper limits of normal, unless determined to be a result of the primary hematologic malignancy or attributed to Gilbert's syndrome
  • Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) or diffusion capacity of the lung of carbon monoxide (DLCO) parameters < 60% predicted (corrected for hemoglobin)
  • Left ventricular ejection fraction (LVEF) < 50% or coronary artery disease requiring treatment
  • Active infection requiring systemic antibiotic therapy with antibacterial, antifungal, or antiviral agents (excluding HIV)
  • Patients who are hepatitis C virus (HCV) antibody positive or hepatitis B virus (HBV) surface antigen positive must be free of clinical evidence of cirrhosis that would otherwise make them ineligible for HCT, as determined by the Principal Investigator (P.I.) in consultation with the Gastrointestinal Service; patients with HBV and ongoing evidence of viral replication may require therapy prior to receiving high-dose chemotherapy
  • Positive serology for Toxoplasma gondii AND requiring treatment or with evidence of active infection
  • Malignancy other than lymphoma, unless 1) in complete remission and more than 5 years from last treatment), or 2) cervical/anal squamous cell carcinoma in situ or 3) superficial basal cell and squamous cell cancers of the skin
  • History of HIV-associated encephalopathy; dementia of any kind; seizures in the past 12 months; any perceived inability to directly provide informed consent (Note: Consent may not be obtained by means of a legal guardian)
  • A medical history of noncompliance with highly active anti-retroviral therapy (HAART) or medical therapy
  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: NCT01769911

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Not yet recruiting
Seattle, Washington, United States, 98109
Contact: Ann E. Woolfrey    206-667-4453      
Principal Investigator: Ann E. Woolfrey         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Ann Woolfrey Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01769911     History of Changes
Other Study ID Numbers: 2583.00, NCI-2012-03168, P30CA015704
Study First Received: January 15, 2013
Last Updated: June 23, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Burkitt Lymphoma
Hodgkin Disease
Immunoblastic Lymphadenopathy
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Hairy Cell
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Follicular
Lymphomatoid Granulomatosis
Waldenstrom Macroglobulinemia
Mycoses
Mycosis Fungoides
Sezary Syndrome
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Lymphoma, T-Cell, Peripheral
Lymphoma, AIDS-Related
Lymphoma, Large-Cell, Anaplastic
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Extranodal NK-T-Cell
Intraocular Lymphoma

ClinicalTrials.gov processed this record on August 26, 2014