Clinical trial NCT01836068: Optimized Antiretroviral Therapy During Allogeneic Hematopoietic Stem Cell Transplantation in HIV-1 Individuals
Official title: Optimized Antiretroviral Therapy During Allogeneic Hematopoietic Stem Cell Transplantation in HIV-1-infected Individuals
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: HIV
Keywords: HIV positive
HIV-1
Bone Marrow Transplant
Allogeneic BMT
BMT
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2013-04-19
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: To find out if it is possible for HIV-1 patients to maintain antiretroviral medications during allogeneic bone marrow transplant

Detailed description: Determine the feasibility of maintaining optimal ART in HIV-1 infected patients during allogeneic hematopoietic stem cell transplant (HSCT). The primary outcome is the fraction of patients who maintain any form of anti-retroviral therapy, including enfuvirtide monotherapy, through day 60 post-transplant. If patients are unable to take oral anti-retroviral medications, but are able to tolerate subcutaneous enfuvirtide monotherapy this will be considered maintenance of ART. Failure to maintain ART will be defined as ≥ 24 hours without any anti-retroviral therapy.

Eligibility criteria: Inclusion Criteria:

* HIV-1 infection, as documented by a rapid HIV-1 test or any FDA-approved HIV-1 enzyme or chemiluminescence immunoassay (E/CIA) test kit and confirmed by western blot at any time prior to study entry. Alternatively, two HIV-1 RNA values \> 200 copies/mL at least 24 hours apart performed by any laboratory that has CLIA certification, or its equivalent may be used to document infection.
* Patients must be ≥ 18 years of age.
* Plan to undergo a Myeloablative, HLA matched or partially HLA-mismatched (haploidentical), related-donor bone marrow transplantation that includes high-dose posttransplantation Cy using bone marrow from a related donor:
* Plan to undergo a Nonmyeloablative, HLA matched or partially HLA-mismatched, related-donor bone marrow transplantation that includes high-dose posttransplantation Cy using bone marrow from a related donor:

Exclusion Criteria:

* Patients with a known history of enfuvirtide resistance will not be eligible for this trial.

Primary outcomes:
measure: Determine the feasibility of maintaining optimal ART in HIV-1 infected patients during allogeneic HSCT
timeFrame: 24 hours
Secondary outcomes:
measure: Number of copies of HIV-1 DNA in blood mononuclear cells at baseline
timeFrame: Baseline
measure: Number of copies of HIV-1 DNA in blood mononuclear cells at 12 weeks
timeFrame: 12 weeks post-intervention
measure: Number of copies of HIV-1 DNA in blood mononuclear cells at 24 weeks
timeFrame: 24 weeks post-intervention
measure: Number of copies of HIV-1 DNA in blood mononuclear cells at 36 weeks
timeFrame: 36 weeks post-intervention
measure: Number of copies of HIV-1 DNA in blood mononuclear cells at 52 weeks
timeFrame: 52 weeks post-intervention
measure: Number of copies of HIV-1 DNA in blood mononuclear cells at 2 years
timeFrame: 2 years post-intervention
Other outcomes:
measure: The incidence of acute graft-vs-host disease
timeFrame: 2 years post-intervention
measure: The severity of acute graft-vs-host disease
timeFrame: 2 years post-intervention
measure: The incidence of chronic graft-vs-host disease as defined by the NIH consensus criteria
timeFrame: 2 years post-intervention
measure: The incidence of chronic graft-vs-host disease as defined by the Seattle criteria
timeFrame: 2 years post-intervention
measure: The severity of chronic graft-vs-host disease as defined by the NIH consensus criteria
timeFrame: 2 years post-intervention
measure: The severity of chronic graft-vs-host disease as defined by the Seattle criteria
timeFrame: 2 years post-intervention
Locations:
city: Baltimore
country: United States
facility: The Sidney Kimmel Comprehensive Cancer Center
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Richard Ambinder, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Capoferri AA, Redd AD, Gocke CD, Clark LR, Quinn TC, Ambinder RF, Durand CM. Brief Report: Rebound HIV Viremia With Meningoencephalitis After Antiretroviral Therapy Interruption After Allogeneic Bone Marrow Transplant. J Acquir Immune Defic Syndr. 2022 Mar 1;89(3):297-302. doi: 10.1097/QAI.0000000000002862.
citation: Capoferri AA, Redd AD, Gocke CD, Clark LR, Ambinder RF, Durand CM. Short Communication: Persistence of HIV After Allogeneic Bone Marrow Transplant in a Dually Infected Individual. AIDS Res Hum Retroviruses. 2022 Jan;38(1):33-36. doi: 10.1089/AID.2021.0047. Epub 2021 Jul 5.
citation: Durand CM, Capoferri AA, Redd AD, Zahurak M, Rosenbloom DIS, Cash A, Avery RK, Bolanos-Meade J, Bollard CM, Bullen CK, Flexner C, Fuchs EJ, Gallant J, Gladstone DE, Gocke CD, Jones RJ, Kasamon YL, Lai J, Levis M, Luznik L, Marr KA, McHugh HL, Mehta Steinke S, Pham P, Pohlmeyer C, Pratz K, Shoham S, Wagner-Johnston N, Xu D, Siliciano JD, Quinn TC, Siliciano RF, Ambinder RF. Allogeneic bone marrow transplantation with post-transplant cyclophosphamide for patients with HIV and haematological malignancies: a feasibility study. Lancet HIV. 2020 Sep;7(9):e602-e610. doi: 10.1016/S2352-3018(20)30073-4. Epub 2020 Jul 7.