Ignite Creation Date:
2024-05-06 @ 8:40 AM
Last Modification Date:
2024-10-26 @ 12:03 PM
Study NCT ID:
NCT02797470
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-08-01
First Post:
2016-06-08
Brief Title:
Gene Therapy in Treating Patients With Human Immunodeficiency Virus-Related Lymphoma Receiving Stem Cell Transplant
Sponsor:
AIDS Malignancy Consortium
Organization:
AIDS Malignancy Consortium
Study Overview
Official Title:
A Phase I Study of Stem Cell Gene Therapy for HIV Mediated by Lentivector Transduced Pre-Selected CD34 Cells
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase III trial studies the side effects and best dose of gene therapy in treating patients with human immunodeficiency virus HIV-related lymphoma that did not respond to therapy or came back after an original response receiving stem cell transplant In gene therapy small stretches of deoxyribonucleic acid DNA called anti-HIV genes are introduced into the stem cells in the laboratory to make the gene therapy product used in this study The type of anti-HIV genes and therapy in this study may make the patients immune cells more resistant to HIV-1 and prevent new immune cells from getting infected with HIV-1
Detailed Description:
PRIMARY OBJECTIVE
I Safety defined as timely engraftment the collective establishment of a persistent absolute neutrophil count of at least 500 cellsmm3 and platelet count of 20000 cellsmm3 without transfusion for 3 consecutive measurements of laboratory values obtained on different days by one month post-transplant in the absence of any grade 3 and 4 non-hematopoietic organ toxicity that can be attributed possibly probably or definitely to lentiviral transduced stem cell transplant excluding alopecia or any clonal expansion and excluding expected toxicities that are associated with the pre-transplant conditioning regimen
SECONDARY OBJECTIVES
I To determine efficacy of the candidate product defined as establishment of 5 mononuclear blood cells expressing anti-HIV genes in the peripheral blood at 3 months post-transplant
II To determine the presence quantity and duration of gene modified HIV-1 resistant peripheral blood cells and gut mucosal immune cells
III To study the integration sites of vector sequences in circulating cells IV To study progression-free survival V To study overall survival VI To study complete response rate and duration VII To study partial response rate and duration VIII To study time to neutrophil engraftment first measurement of 3 consecutive laboratory values on different days of absolute neutrophil count ANC 500 cellsmm3
IX To study time to platelet engraftment first measurement of 3 consecutive measurements laboratory values obtained on different days of platelets 20000 cellsmm3 without platelet transfusions 7 days prior
X To study hematologic function at day 100 ANC 1500 hemoglobin Hb 10 gdl without transfusion and platelets 100000 XI To study CD4 recovery at the conclusion of the trial XII To study safety in terms of toxicities infections transfusions and infusion-related reactions
XIII To study HIV-1 viral load over time XIV To study persistence of vector-transduced cells over time
EXPLORATORY OBJECTIVE
I To evaluate the presence and the magnitude of expansion of HIV-1 resistant immune cells in the peripheral blood and gut mucosa of transplanted participants subsequent to withholding anti-retroviral therapy ART
OUTLINE This is a dose-escalation study of lentivirus vector CCR5 shRNATRIM5alphaTAR decoy-transduced autologous CD34-positive hematopoietic progenitor cells
Patients receive BEAM or BEAM-R regimen administered as standard of care comprising carmustine on day -6 cytarabine twice daily BID on days -5 to -2 etoposide BID on days -5 to -2 and melphalan on day -1 Patients with B-cell lymphoma also receive rituximab on day -6 before chemotherapy and on days 21 and 28 post-transplant as standard of care Patients undergo intravenous IV infusion of lentivirus vector CCR5 shRNATRIM5alphaTAR decoy-transduced autologous CD34-positive hematopoietic progenitor cells over 1 hour
After completion of study treatment patients are followed up at days 7 14 21 28 42 60 90 120 180 240 300 360 420 480 520 600 660 and 720 and then yearly for at least 15 years
I Safety defined as timely engraftment the collective establishment of a persistent absolute neutrophil count of at least 500 cellsmm3 and platelet count of 20000 cellsmm3 without transfusion for 3 consecutive measurements of laboratory values obtained on different days by one month post-transplant in the absence of any grade 3 and 4 non-hematopoietic organ toxicity that can be attributed possibly probably or definitely to lentiviral transduced stem cell transplant excluding alopecia or any clonal expansion and excluding expected toxicities that are associated with the pre-transplant conditioning regimen
SECONDARY OBJECTIVES
I To determine efficacy of the candidate product defined as establishment of 5 mononuclear blood cells expressing anti-HIV genes in the peripheral blood at 3 months post-transplant
II To determine the presence quantity and duration of gene modified HIV-1 resistant peripheral blood cells and gut mucosal immune cells
III To study the integration sites of vector sequences in circulating cells IV To study progression-free survival V To study overall survival VI To study complete response rate and duration VII To study partial response rate and duration VIII To study time to neutrophil engraftment first measurement of 3 consecutive laboratory values on different days of absolute neutrophil count ANC 500 cellsmm3
IX To study time to platelet engraftment first measurement of 3 consecutive measurements laboratory values obtained on different days of platelets 20000 cellsmm3 without platelet transfusions 7 days prior
X To study hematologic function at day 100 ANC 1500 hemoglobin Hb 10 gdl without transfusion and platelets 100000 XI To study CD4 recovery at the conclusion of the trial XII To study safety in terms of toxicities infections transfusions and infusion-related reactions
XIII To study HIV-1 viral load over time XIV To study persistence of vector-transduced cells over time
EXPLORATORY OBJECTIVE
I To evaluate the presence and the magnitude of expansion of HIV-1 resistant immune cells in the peripheral blood and gut mucosa of transplanted participants subsequent to withholding anti-retroviral therapy ART
OUTLINE This is a dose-escalation study of lentivirus vector CCR5 shRNATRIM5alphaTAR decoy-transduced autologous CD34-positive hematopoietic progenitor cells
Patients receive BEAM or BEAM-R regimen administered as standard of care comprising carmustine on day -6 cytarabine twice daily BID on days -5 to -2 etoposide BID on days -5 to -2 and melphalan on day -1 Patients with B-cell lymphoma also receive rituximab on day -6 before chemotherapy and on days 21 and 28 post-transplant as standard of care Patients undergo intravenous IV infusion of lentivirus vector CCR5 shRNATRIM5alphaTAR decoy-transduced autologous CD34-positive hematopoietic progenitor cells over 1 hour
After completion of study treatment patients are followed up at days 7 14 21 28 42 60 90 120 180 240 300 360 420 480 520 600 660 and 720 and then yearly for at least 15 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2015-01745 | REGISTRY | None | None |
| 9933 | OTHER | None | None |
| AMC 097 | OTHER | None | None |
| 097 | OTHER | None | None |
| AMC-097 | OTHER | None | None |
| U01CA121947 | NIH | CTEP | httpsreporternihgovquickSearchU01CA121947 |