Stage IV Adult Hodgkin Lymphoma Clinical Trial
Official title:
A Clinical Trial of Gene-Modified Stem Cells to Generate HIV-Resistant Cells in Conjunction With Standard Chemotherapy for Treatment of Lymphoma in Patients With HIV Infection
This pilot phase I trial studies the side effects and best dose of human immunodeficiency virus (HIV)-resistant gene modified stem cells in treating HIV-positive patients who are undergoing first-line treatment for Hodgkin or Non-Hodgkin Lymphoma. Stem cells are collected from the patient and HIV-resistance genes are placed into the stem cells. The stem cells are then re-infused into the patient. These genetically modified stem cells may help the body make cells that are resistant to HIV infection.
PRIMARY OBJECTIVES:
I. To determine the safety and feasibility of infusing C46/CCR5/P140K lentiviral
vector-transduced autologous hematopoietic stem progenitor cells (HSPC) (gene modified,
HIV-protected HSPC) after standard first line treatment of lymphoma in patients with HIV
infection.
II. To determine the dose of carmustine (BCNU) in combination with O6-benzylguanine (O6BG)
that results in selection in vivo of gene-modified HIV resistant cells with minimal toxicity.
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 highly active
antiretroviral therapy (HAART) interruption.
SECONDARY OBJECTIVES:
I. Evaluate the molecular and clonal composition of gene-modified cells after standard first
line treatment.
II. Evaluate the molecular and clonal composition of gene-modified cells after O6BG/BCNU.
III. Determine the correlation between the level of MGMT(P140K) marking with toxicity and
response to O6BG/BCNU chemotherapy.
IV. Characterize the toxicity associated with in vivo selection.
V. Describe 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:
MOBILIZATION AND HSPC COLLECTION: Between the second and the last course of planned standard
chemotherapy, patients undergo mobilization of peripheral blood stem cells with filgrastim
subcutaneously (SC) beginning the day after the last dose of chemotherapy in the previous
cycle. If CD34 cell count in peripheral blood at least 24 hours after recovery from nadir is
>= 40 CD34 cells/mcL, patients will undergo apheresis collection the next day. If CD34 cell
count is < 40 CD34 cells/mcL, plerixafor SC will be administered and patients will undergo
apheresis collection the next day. Patients undergo apheresis until a total apheresis product
of >= 4.0 x 10^6 CD34+ cells/kg are collected.
STEM CELL INFUSION: Patients receive CD34+ gene-modified C46/CCR5/P140K lentiviral
vector-transduced autologous HSPC intravenously (IV) within 2 to 8 days, but no later than 28
days, after completion of the last cycle of first line treatment for lymphoma.
IN VIVO SELECTION WITH O6-BENZYLGUANINE AND CARMUSTINE: Between 28-180 days after infusion of
gene-modified HSPC and after hematopoietic recovery from first line treatment, patients with
>= 1% and < 10% gene marked cells receive O6-benzylguanine IV over 1 hour, immediately
followed by carmustine IV, and followed 7-8 hours later by O6-benzylguanine IV over 1 hour.
Treatment continues for an additional course provided that gene marked cells does not meet or
exceed 10% of peripheral blood cells and in the absence of unacceptable toxicity.
STRUCTURED TREATMENT INTERRUPTION (STI): Patients achieving >= 10% gene marked cells for 2
consecutive months following infusion of gene-modified HSPC and with CD4+ cell counts and
total lymphocyte counts at baseline begin STI of HAART for up to 12 weeks. Patients resume
HAART if one of the following criteria occurs: 1) CD4 count < 350 cells/mcL or decline in
percent CD4+ cells by > 33% from baseline for three consecutive evaluations; 2) increase in
HIV RNA > 100,000 copies/mL on two consecutive evaluations; 3) 12 weeks have passed since
discontinuation of HAART; or 4) at the discretion of the infectious disease (ID) consultant
or principal investigator (PI).
* If patient is not on an efavirenz-containing regimen, HAART is discontinued simultaneously.
If patient is on an efavirenz-containing regimen, patients will switch from efavirenz to an
integrase inhibitor for at least 2 weeks and then discontinue HAART simultaneously.
After completion of study treatment, patients are followed up for 2 years, every 6 months for
3 years and then annually for 15 years.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT01233921 -
Palifermin in Preventing Chronic Graft-Versus-Host Disease in Patients Who Have Undergone Donor Stem Cell Transplant for Hematologic Cancer
|
N/A | |
Completed |
NCT01588015 -
Vaccine Therapy in Preventing Cytomegalovirus Infection in Patients With Hematological Malignancies Undergoing Donor Stem Cell Transplant
|
Phase 1 | |
Completed |
NCT00608361 -
Dasatinib in Treating Patients With Solid Tumors or Lymphomas That Are Metastatic or Cannot Be Removed By Surgery
|
Phase 1 | |
Terminated |
NCT00288067 -
Fenretinide and Rituximab in Treating Patients With B-Cell Non-Hodgkin Lymphoma
|
Phase 1/Phase 2 | |
Completed |
NCT00098891 -
MS-275 and Isotretinoin in Treating Patients With Metastatic or Advanced Solid Tumors or Lymphomas
|
Phase 1 | |
Completed |
NCT00004241 -
17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Advanced Epithelial Cancer, Malignant Lymphoma, or Sarcoma
|
Phase 1 | |
Active, not recruiting |
NCT01476410 -
Brentuximab Vedotin and Combination Chemotherapy in Treating Older Patients With Previously Untreated Stage II-IV Hodgkin Lymphoma
|
Phase 2 | |
Withdrawn |
NCT01165645 -
Lopinavir and Ritonavir in Improving Immune Response to Vaccines in Patients With Complete Remission Following A Bone Marrow Transplant for Hodgkin Lymphoma
|
N/A | |
Terminated |
NCT00096005 -
Tanespimycin and Bortezomib in Treating Patients With Advanced Solid Tumors or Lymphomas
|
Phase 1 | |
Terminated |
NCT00101244 -
SB-715992 in Treating Patients With Metastatic or Unresectable Solid Tumors or Hodgkin's or Non-Hodgkin's Lymphoma
|
Phase 1 | |
Completed |
NCT00112593 -
Fludarabine and Total-Body Irradiation Followed By Donor Stem Cell Transplant and Cyclosporine and Mycophenolate Mofetil in Treating HIV-Positive Patients With or Without Cancer
|
N/A | |
Completed |
NCT01129193 -
AR-42 in Treating Patients With Advanced or Relapsed Multiple Myeloma, Chronic Lymphocytic Leukemia, or Lymphoma
|
Phase 1 | |
Withdrawn |
NCT01558778 -
Mechanical Stimulation in Preventing Bone Density Loss in Patients Undergoing Donor Stem Cell Transplant
|
N/A | |
Completed |
NCT00458731 -
Bevacizumab and Cediranib Maleate in Treating Patients With Metastatic or Unresectable Solid Tumor, Lymphoma, Intracranial Glioblastoma, Gliosarcoma or Anaplastic Astrocytoma
|
Phase 1 | |
Terminated |
NCT00354185 -
PXD101 and 17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphoma
|
Phase 1 | |
Terminated |
NCT01805037 -
Brentuximab Vedotin + Rituximab as Frontline Therapy for Pts w/ CD30+ and/or EBV+ Lymphomas
|
Phase 1/Phase 2 | |
Completed |
NCT01959477 -
Dose Monitoring of Busulfan and Combination Chemotherapy in Hodgkin or Non-Hodgkin Lymphoma Undergoing Stem Cell Transplant
|
Phase 0 | |
Completed |
NCT00348985 -
PXD101 and Bortezomib in Treating Patients With Advanced Solid Tumors or Lymphomas
|
Phase 1 | |
Terminated |
NCT00060112 -
Oblimersen and Gemcitabine in Treating Patients With Advanced Solid Tumor or Lymphoma
|
Phase 1 | |
Completed |
NCT02298257 -
A Pilot Trial of AVD and Brentuximab Vedotin (SGN-35) in the Treatment of Stage III-IV HIV-associated Hodgkin Lymphoma
|
Phase 2 |