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Clinical Trial Details — Status: Withdrawn

Administrative data

NCT number NCT01769911
Other study ID # 2583.00
Secondary ID NCI-2012-03168P3
Status Withdrawn
Phase N/A
First received January 15, 2013
Last updated May 6, 2015
Start date February 2015

Study information

Verified date May 2015
Source Fred Hutchinson Cancer Research Center
Contact n/a
Is FDA regulated No
Health authority United States: Federal Government
Study type Interventional

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


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.


Recruitment information / eligibility

Status Withdrawn
Enrollment 0
Est. completion date
Est. primary completion date February 2019
Accepts healthy volunteers No
Gender Both
Age group 18 Years to 66 Years
Eligibility 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

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

Intervention

Drug:
carmustine
Given IV
cytarabine
Given IV
melphalan
Given IV
etoposide
Given IV
O6-benzylguanine
Given IV
Procedure:
autologous hematopoietic stem cell transplantation
Undergo transduced and/or non-transduced transplant
peripheral blood stem cell transplantation
Undergo transduced and/or non-transduced transplant
Other:
laboratory biomarker analysis
Correlative studies

Locations

Country Name City State
United States Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle Washington

Sponsors (2)

Lead Sponsor Collaborator
Fred Hutchinson Cancer Research Center National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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) Up to day 180 Yes
Primary 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 Up to day 180 Yes
Primary 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 During the 12 weeks without HAART Yes
Primary 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 Up to 3 months No
Primary Efficacy of infusion of gene-modified cells, defined as engraftment of at least1% gene-modified cells Up to 3 months No
Primary Efficacy of O6BG/BCNU in vivo selection, defined as selection of gene-modified cells to a level at least 10% of peripheral blood cells Up to 3 months No
See also
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Completed NCT01527045 - Donor Atorvastatin Treatment in Preventing Severe Acute GVHD After Nonmyeloablative Peripheral Blood Stem Cell Transplant in Patients With Hematological Malignancies Phase 2
Active, not recruiting NCT02153580 - Cellular Immunotherapy Following Chemotherapy in Treating Patients With Recurrent Non-Hodgkin Lymphomas, Chronic Lymphocytic Leukemia, or B-Cell Prolymphocytic Leukemia Phase 1
Active, not recruiting NCT01955499 - Lenalidomide and Ibrutinib in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma Phase 1
Terminated NCT02109224 - Ibrutinib in Treating Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma in Patients With HIV Infection Phase 1
Completed NCT01427881 - Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies Phase 2
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Completed NCT01093586 - Donor Umbilical Cord Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies Phase 2
Terminated NCT00383565 - FR901228 in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma Phase 2
Completed NCT00253630 - Vorinostat in Treating Patients With Low-Grade Non-Hodgkin's Lymphoma Phase 2
Completed NCT00078858 - Mycophenolate Mofetil and Cyclosporine in Reducing Graft-Versus-Host Disease in Patients With Hematologic Malignancies or Metastatic Kidney Cancer Undergoing Donor Stem Cell Transplant Phase 1/Phase 2
Completed NCT00006473 - Oxaliplatin in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma Phase 2
Completed NCT00003196 - Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed by Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma N/A
Active, not recruiting NCT01318317 - Genetically Engineered Lymphocyte Therapy After Peripheral Blood Stem Cell Transplant in Treating Patients With High-Risk, Intermediate-Grade, B-cell Non-Hodgkin Lymphoma Phase 1/Phase 2
Terminated NCT01678443 - Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies Phase 1
Completed NCT01921387 - Radiolabeled Monoclonal Antibody and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With High-Risk Lymphoid Malignancies Phase 1/Phase 2
Active, not recruiting NCT01815749 - Genetically Modified T-cell Infusion Following Peripheral Blood Stem Cell Transplant in Treating Patients With Recurrent or High-Risk Non-Hodgkin Lymphoma Phase 1
Recruiting NCT04007029 - Modified Immune Cells (CD19/CD20 CAR-T Cells) in Treating Patients With Recurrent or Refractory B-Cell Lymphoma or Chronic Lymphocytic Leukemia Phase 1
Completed NCT01267812 - Bortezomib and Rituximab in Treating Patients With Mantle Cell Lymphoma Who Have Previously Undergone Stem Cell Transplantation Phase 2
Completed NCT01588015 - Vaccine Therapy in Preventing Cytomegalovirus Infection in Patients With Hematological Malignancies Undergoing Donor Stem Cell Transplant Phase 1