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Clinical Trial Summary

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


Clinical Trial 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. ;


Study Design

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


Related Conditions & MeSH terms

  • 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
  • Burkitt 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
  • Hodgkin Disease
  • Intraocular Lymphoma
  • Leukemia
  • Leukemia, Hairy Cell
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, T-Cell
  • Leukemia-Lymphoma, Adult T-Cell
  • Lymphoma
  • Lymphoma, AIDS-Related
  • Lymphoma, B-Cell
  • Lymphoma, B-Cell, Marginal Zone
  • Lymphoma, Extranodal NK-T-Cell
  • Lymphoma, Follicular
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Large-Cell, Anaplastic
  • Lymphoma, Large-Cell, Immunoblastic
  • Lymphoma, Mantle-Cell
  • Lymphoma, Non-Hodgkin
  • Lymphoma, T-Cell
  • Lymphoma, T-Cell, Cutaneous
  • Lymphoma, T-Cell, Peripheral
  • Lymphomatoid Granulomatosis
  • Mycosis Fungoides
  • 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
  • Sezary Syndrome
  • 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
  • Waldenstrom Macroglobulinemia
  • Waldenström Macroglobulinemia

NCT number NCT01769911
Study type Interventional
Source Fred Hutchinson Cancer Research Center
Contact
Status Withdrawn
Phase N/A
Start date February 2015

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