Allogeneic Transplant in HIV Patients (BMT CTN 0903)

NCT01410344 | Completed Phase 2 Results DMC

• 4 other identifiers: BMTCTN0903U01HL069294BMT CTN 09035U24CA076518
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 11

Brief Summary

The rationale for this trial is to demonstrate the feasibility and safety of allogeneic HCT for patients with chemotherapy-sensitive hematological malignancies and coincident HIV-infection. In particular, the trial will focus on the 100-day non-relapse mortality as an indicator of the safety of transplant in this patient population. Correlative assays will focus upon the incidence of infectious complications in this patient population, the evolution of HIV infection and immunological reconstitution. Where feasible (and when this can be accomplished without compromise of either the donor quality or the timeliness of transplantation), an attempt will be made to identify donors who are homozygotes for the delta32 mutation for CCR5.

Conditions

Leukemia; Lymphoma; HIV

Keywords

HIV; ALL; AML; MDS; Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Non-Relapse Mortality

  The events for non-relapse mortality are death due to any cause other than relapse of the underlying malignancy.

  Day 100, 1 Year, and 2 Years Post-transplant

Secondary Outcomes (9)

• Percentage of Participants With Overall Survival

  Six months, 1 Year, and 2 Years Post-transplant

• Percentage of Participants With Relapse/Progression

  1 Year Post-transplant

• Primary Cause of Death

  Up to 2 Years Post-transplant

• Disease Status

  Day 100 Post-transplant

• Percentage of Participants Recovering Hematologic Function

  Days 28 and 100 Post-transplant

Study Arms (1)

Allogeneic Transplant

OTHER

One regimen from either reduced-intensity conditioning (RIC) (Fludarabine and Busulfan; or Fludarabine and Melphalan) or myeloablative conditioning (MAC) (Busulfan and Fludarabine; or Cyclophosphamide and Total Body Irradiation) will be administered prior to allogeneic hematopoietic cell transplantation (HCT).

Drug: Fludarabine and Busulfan; Drug: Fludarabine and Melphalan; Drug: Busulfan and Fludarabine; Drug: Cyclophosphamide and Total Body Irradiation

Interventions

Fludarabine and Busulfan DRUG

RIC Regimen (Flu/Bu): Fludarabine total dose: 120-180 mg/m\^2, Busulfan: ≤ 8 mg/kg PO or 6.4 mg/kg IV). Recommended regimen: * Days -6 to -2: Flu (30 mg/m\^2/day, total dose of 150 mg/m\^2) * Days -5 to -4: Busulfan (4mg/kg/day PO or 3.2 mg/kg IV, 130 mg/m\^2/day, total dose of 8 mg/kg PO or 6.4 mg/kg IV, or 260 mg/m\^2 IV, respectively) Patients with a creatinine clearance of 40-70 ml/min (measured or calculated) should have a 20 percent dose reduction in Fludarabine dosage. Busulfan will be dosed according to the recipient's ideal body weight (IBW), unless the patient weighs more than 125 percent of IBW, in which case the drug will be dosed according to the adjusted IBW.

Also known as: Fludara and Busulfex

Allogeneic Transplant

Fludarabine and Melphalan DRUG

RIC Regimen (Flu/Mel): Fludarabine total dose: 120-180 mg/m\^2, Melphalan total dose: less than or equal to 150 mg/m\^2. Recommended regimen: * Days -5 to -2: Flu (30mg/m\^2/day, total dose of 120 mg/m\^2) * Day -1: Mel (140mg/m\^2) Patients with a creatinine clearance of 40-70 ml/min (measured or calculated) should have a 20 percent dose reduction in Fludarabine dosage.

Also known as: Fludara and Alkeran

Allogeneic Transplant

Busulfan and Fludarabine DRUG

MAC Regimen (Bu/Flu): Fludarabine total dose: 120-180mg/m\^2 Busulfan total dose less than or equal to 16mg/kg PO or 12.8 mg/kg IV. Recommended regimen: * Days -5 to -2: Busulfan (4 mg/kg/day PO with Bu Css 900 plus/equal to 100 ng/mL (or per institutional standard), 3.2 mg/kg/day IV or 130 mg/m\^2/day IV; total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m\^2, respectively) * Days -5 to -2: Flu (30 mg/m\^2/day, total dose of 120 mg/m\^2) Patients with a creatinine clearance of 40-70 ml/min (measured or calculated) should have a 20 percent dose reduction in Fludarabine dosage. Busulfan will be dosed according to the recipient's ideal body weight (IBW), unless the patient weighs more than 125 percent of IBW, in which case the drug will be dosed according to the adjusted IBW.

Also known as: Busulfex and Fludara

Allogeneic Transplant

Cyclophosphamide and Total Body Irradiation DRUG

MAC Regimen (Cy/TBI): Cyclophosphamide total dose: 120 mg/kg, Fractionated TBI total dose: 1200-1420 cGy Recommended regimen: * Days -7 to -4: TBI (total dose of 1200-1420 cGy) * Days -3 to -2: Cy (60 mg/kg/day, total dose of 120 mg/kg) Cyclophosphamide will be dosed according to the recipient's ideal body weight (IBW), unless the patient weighs less than IBW, in which case the drug will be dosed according to the actual body weight.

Also known as: Cytoxan® and radiation

Allogeneic Transplant

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 infection, as documented by a rapid HIV 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. HIV antigen, plasma HIV-1 RNA, or a secondary antibody test by a method other than rapid HIV and E/CIA is acceptable as an alternative test. Alternatively, if a rapid HIV test or any FDA-Approved HIV-1 Enzyme or Chemiluminescence Immunoassay (E/CIA) test is not available, two HIV-1 RNA values ≥ 2000 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 willing to comply with effective Antiretroviral Therapy.
• Patients must be ≥ 15 years of age.
• Hematological malignancy associated with a poor prognosis with medical therapy alone. Diagnoses to be included:
• Patients with the diagnosis of Acute Myeloid or Lymphocytic Leukemia (AML or ALL) in first or second complete remission.
• Hodgkin Lymphoma beyond first remission achieving at least a partial response to most recent therapy with no evidence of progression prior to transplant.
• Non-Hodgkin Lymphoma beyond first remission achieving at least a partial response to most recent therapy with no evidence of progression prior to transplant.
• Donor/Recipient HLA Matching:
• Related donor: must be an 8/8 match at HLA-A, -B, -C, (serologic typing or higher resolution) and -DRB1 (at high resolution using DNA based typing). A 7/8 related donor match is permitted only if an 8/8 unrelated donor cannot be identified.
• Unrelated donor: must be a 7/8 or 8/8 match at HLA-A, -B, -C, and -DRB1 (at high resolution using DNA based typing).
• Patients with adequate organ function as measured by:
• Cardiac: Left ventricular ejection fraction at rest ≥ 40% demonstrated by Multi Gated Acquisition Scan (MUGA) or echocardiogram. Patients with known heart disease must have a functional status no worse than American Heart Association Class I defined as patients with cardiac disease but without resulting limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain.
• Hepatic:
• i. Total Bilirubin \< 2.0 mg/dL (except for isolated hyperbilirubinemia attributed to Gilbert syndrome or antiretroviral therapy as specified in Appendix E) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 5x the upper limit of normal.
• ii. Concomitant Hepatitis: Patients with chronic hepatitis B or C may be enrolled on the trial providing the above bilirubin and transaminase criteria are met. In addition, there must be no clinical or pathologic evidence of irreversible chronic liver disease, and there must be no active viral replication as evidenced by an undetectable hepatitis viral load by a PCR-based assay.

You may not qualify if:

• Karnofsky/Lansky performance score \< 70%.
• Active central nervous system (CNS) malignancy; however, patients with a history of positive Cerebrospinal fluid (CSF) cytology that has become negative with intrathecal chemotherapy are eligible.
• Uncontrolled bacterial, viral or fungal infection (currently taking medication and with progression or no clinical improvement).
• Active Cytomegalovirus (CMV) retinitis or other CMV-related organ dysfunction.
• AIDS related syndromes or symptoms that pose a perceived excessive risk for transplantation-related morbidity as determined by the principal investigator.
• Untreatable HIV infection due to multidrug antiretroviral resistance. Patients with a detectable viral load \> 750 copies/ml should be evaluated with an HIV drug resistance test (HIV-1 genotype). The results should be included as part of the Antiretroviral Review (described in Appendix D). This Review Committee will make the final determination as to whether HIV viremia could potentially be suppressed with alternate antiretroviral therapy. .
• Pregnant (positive β-HCG) or breastfeeding.
• Fertile men or women unwilling to use contraceptive techniques from the time of initiation of mobilization until six-months post-transplant.
• Prior allogeneic HCT.
• Patients with psychosocial conditions that would prevent study compliance and follow-up, as determined by the principal investigator.
• T-cell depletion (including ATG or alemtuzumab) is not allowed.
• Use of cord blood as the source of hematopoietic cells is not allowed.

Sponsors & Collaborators

• Medical College of Wisconsin: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Cancer Institute (NCI): collaborator
• Blood and Marrow Transplant Clinical Trials Network: collaborator
• National Marrow Donor Program: collaborator

Study Sites (11)

Mayo Clinic - Phoenix

Phoenix, Arizona, 85054, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

University of CA, SF

San Francisco, California, 94143-0324, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33624, United States

Location

Blood & Marrow Transplant Program at Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

University of Pennsylvania Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

University of Texas/MD Anderson CRC

Houston, Texas, 77030, United States

Location

Texas Transplant Institute

San Antonio, Texas, 78229, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53211, United States

Location

Related Publications (2)

• Scott BL, Pasquini MC, Logan BR, Wu J, Devine SM, Porter DL, Maziarz RT, Warlick ED, Fernandez HF, Alyea EP, Hamadani M, Bashey A, Giralt S, Geller NL, Leifer E, Le-Rademacher J, Mendizabal AM, Horowitz MM, Deeg HJ, Horwitz ME. Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes. J Clin Oncol. 2017 Apr 10;35(11):1154-1161. doi: 10.1200/JCO.2016.70.7091. Epub 2017 Feb 13.

  PMID: 28380315 RESULT

• Ambinder RF, Wu J, Logan B, Durand CM, Shields R, Popat UR, Little RF, McMahon DK, Cyktor J, Mellors JW, Ayala E, Kaplan LD, Noy A, Jones RJ, Howard A, Forman SJ, Porter D, Arce-Lara C, Shaughnessy P, Sproat L, Hashmi SK, Mendizabal AM, Horowitz MM, Navarro WH, Alvarnas JC. Allogeneic Hematopoietic Cell Transplant for HIV Patients with Hematologic Malignancies: The BMT CTN-0903/AMC-080 Trial. Biol Blood Marrow Transplant. 2019 Nov;25(11):2160-2166. doi: 10.1016/j.bbmt.2019.06.033. Epub 2019 Jul 4.

  PMID: 31279752 DERIVED

MeSH Terms

Conditions

Leukemia; Lymphoma; Lymphoma, Non-Hodgkin

Interventions

fludarabine; Busulfan; fludarabine phosphate; Melphalan; Cyclophosphamide; Whole-Body Irradiation; Radiation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Phosphoramide Mustards; Phosphoramides; Organophosphorus Compounds; Radiotherapy; Therapeutics; Investigative Techniques; Physical Phenomena

Results Point of Contact

• Title: Adam Mendizabal, PhD
• Organization: The Emmes Corporation

amendizabal@emmes.com

301-251-1161

Study Officials

• Mary Horowitz, MD

  Center for International Blood and Marrow Transplant Research

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2011
• First Posted: August 5, 2011
• Study Start: September 1, 2011
• Primary Completion: November 1, 2016
• Study Completion: June 1, 2018
• Last Updated: December 8, 2022
• Results First Posted: May 24, 2018

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Within 6 months of official study closure at participating sites.
• Access Criteria: Available to the public

Locations

US (11)