Optimized Antiretroviral Therapy During Allogeneic Hematopoietic Stem Cell Transplantation in HIV-1 Individuals

Optimized Antiretroviral Therapy During Allogeneic Hematopoietic Stem Cell Transplantation in HIV-1-infected Individuals

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

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Drug: Enfuvirtide

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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • The Sidney Kimmel Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Enfuvirtide monotherapy; Enfuvirtide 90 mg subcutaneously every 12 hours will be also be administered during any periods when oral medications are not expected to be tolerated for ≥ 24 hours, or during periods when ART is held due to interactions with conditioning regimens in patients who require ritonavir-boosted PI containing ART regimens.	Drug: Enfuvirtide; Enfuvirtide 90 mg subcutaneously twice daily will be administered to all patients on day 3 and 4 post-transplant and during any periods when oral medications are not expected to be tolerated for ≥ 24 hours, or during periods when ART is held due to interactions; Other Names: Fuzeon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the feasibility of maintaining optimal ART in HIV-1 infected patients during allogeneic HSCT	Failure to maintain anti retroviral therapy for 24 hours	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of copies of HIV-1 DNA in blood mononuclear cells at baseline	Measure the number of copies of HIV-1 DNA per million peripheral blood mononuclear cells.	Baseline
Number of copies of HIV-1 DNA in blood mononuclear cells at 12 weeks	Measure the number of copies of HIV-1 DNA per million peripheral blood mononuclear cells.	12 weeks post-intervention
Number of copies of HIV-1 DNA in blood mononuclear cells at 24 weeks	Measure the number of copies of HIV-1 DNA per million peripheral blood mononuclear cells.	24 weeks post-intervention
Number of copies of HIV-1 DNA in blood mononuclear cells at 36 weeks	Measure the number of copies of HIV-1 DNA per million peripheral blood mononuclear cells.	36 weeks post-intervention
Number of copies of HIV-1 DNA in blood mononuclear cells at 52 weeks	Measure the number of copies of HIV-1 DNA per million peripheral blood mononuclear cells.	52 weeks post-intervention
Number of copies of HIV-1 DNA in blood mononuclear cells at 2 years	Measure the number of copies of HIV-1 DNA per million peripheral blood mononuclear cells.	2 years post-intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of acute graft-vs-host disease	Describe the incidence of acute graft-vs-host disease via the Keystone criteria	2 years post-intervention
The severity of acute graft-vs-host disease	Describe the severity of acute graft-vs-host disease via the Keystone criteria	2 years post-intervention
The incidence of chronic graft-vs-host disease as defined by the NIH consensus criteria	Describe the incidence chronic graft-vs-host disease via the NIH consensus criteria.	2 years post-intervention
The incidence of chronic graft-vs-host disease as defined by the Seattle criteria	Describe the incidence chronic graft-vs-host disease via the Seattle criteria.	2 years post-intervention
The severity of chronic graft-vs-host disease as defined by the NIH consensus criteria	Describe the severity of chronic graft-vs-host disease via the NIH consensus criteria and the Seattle criteria	2 years post-intervention
The severity of chronic graft-vs-host disease as defined by the Seattle criteria	Describe the severity of chronic graft-vs-host disease via the Seattle criteria	2 years post-intervention

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Richard Ambinder, M.D., Ph.D., Johns Hopkins University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2013
• Primary Completion (Actual): January 22, 2020
• Study Completion (Actual): June 5, 2021

Study Registration Dates

• First Submitted: April 16, 2013
• First Submitted That Met QC Criteria: April 18, 2013
• First Posted (Estimate): April 19, 2013

Study Record Updates

• Last Update Posted (Actual): November 23, 2021
• Last Update Submitted That Met QC Criteria: November 22, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: HIV-1; HIV positive; BMT; Bone Marrow Transplant; Allogeneic BMT
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; Enfuvirtide
• Other Study ID Numbers: J1331; NA_00083734 (Other Identifier: Johns Hopkins); 1P30AI094189-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No