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

NCT01836068 | Completed Early Phase 1 DMC FDA Drug

• 3 other identifiers: J1331NA_000837341P30AI094189-01A1
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

HIV

Keywords

HIV positive; HIV-1; Bone Marrow Transplant; Allogeneic BMT; BMT

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Number of copies of HIV-1 DNA in blood mononuclear cells at baseline

  Baseline

• Number of copies of HIV-1 DNA in blood mononuclear cells at 12 weeks

  12 weeks post-intervention

• Number of copies of HIV-1 DNA in blood mononuclear cells at 24 weeks

  24 weeks post-intervention

• Number of copies of HIV-1 DNA in blood mononuclear cells at 36 weeks

  36 weeks post-intervention

• Number of copies of HIV-1 DNA in blood mononuclear cells at 52 weeks

  52 weeks post-intervention

Other Outcomes (6)

• The incidence of acute graft-vs-host disease

  2 years post-intervention

• The severity of acute graft-vs-host disease

  2 years post-intervention

• The incidence of chronic graft-vs-host disease as defined by the NIH consensus criteria

  2 years post-intervention

Study Arms (1)

Enfuvirtide monotherapy

EXPERIMENTAL

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

Interventions

Enfuvirtide DRUG

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

Also known as: Fuzeon

Enfuvirtide monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

The Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

Location

Related Publications (3)

• 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.

  PMID: 34753870 DERIVED

• 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.

  PMID: 34107771 DERIVED

• 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.

  PMID: 32649866 DERIVED

MeSH Terms

Conditions

HIV Seropositivity

Interventions

Enfuvirtide

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; HIV Envelope Protein gp41; Viral Fusion Proteins; Membrane Fusion Proteins; Membrane Proteins; Proteins; HIV Antigens; Antigens, Viral; Viral Proteins; env Gene Products, Human Immunodeficiency Virus; Gene Products, env; Retroviridae Proteins; Human Immunodeficiency Virus Proteins; Viral Envelope Proteins; Viral Structural Proteins; Antigens; Biological Factors

Study Officials

• Richard Ambinder, M.D., Ph.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2013
• First Posted: April 19, 2013
• Study Start: June 1, 2013
• Primary Completion: January 22, 2020
• Study Completion: June 5, 2021
• Last Updated: November 23, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)