- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01410344
Allogeneic Transplant in HIV Patients (BMT CTN 0903)
Allogeneic Hematopoietic Cell Transplant for Hematological Cancers and Myelodysplastic Syndromes in HIV-Infected Individuals (BMT CTN #0903)
Study Overview
Status
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Arizona
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Phoenix, Arizona, United States, 85054
- Mayo Clinic - Phoenix
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California
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Duarte, California, United States, 91010
- City of Hope National Medical Center
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San Francisco, California, United States, 94143-0324
- University of CA, SF
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Florida
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Tampa, Florida, United States, 33624
- H. Lee Moffitt Cancer Center
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Georgia
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Atlanta, Georgia, United States, 30342
- Blood & Marrow Transplant Program at Northside Hospital
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Maryland
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Baltimore, Maryland, United States, 21231
- Johns Hopkins
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Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic - Rochester
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- University of Pennsylvania Cancer Center
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Texas
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Houston, Texas, United States, 77030
- University of Texas/MD Anderson CRC
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San Antonio, Texas, United States, 78229
- Texas Transplant Institute
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Wisconsin
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Milwaukee, Wisconsin, United States, 53211
- Medical College of Wisconsin
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
- Patients with advanced myelodysplastic syndromes (MDS), including those with International Prognostic Scoring System (IPSS) Int-2 and high-risk disease with less than 10% marrow blasts and no circulating myeloblasts after most recent therapy. Patients with acute leukemia that develops from a pre-existing MDS must meet the inclusion criteria for patients with AML detailed above.
- 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.
c) Renal: Creatinine clearance (calculated creatinine clearance is permitted) > 40 mL/min.
d) Pulmonary: Diffusing capacity of the lung for carbon monoxide (DLCO), forced expiratory volume in one second (FEV1), or forced vital capacity (FVC) ≥ 45% of predicted (corrected for hemoglobin).
- Signed Informed Consent
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Other: Allogeneic Transplant
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).
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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:
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.
Other Names:
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:
Patients with a creatinine clearance of 40-70 ml/min (measured or calculated) should have a 20 percent dose reduction in Fludarabine dosage.
Other Names:
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:
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.
Other Names:
MAC Regimen (Cy/TBI): Cyclophosphamide total dose: 120 mg/kg, Fractionated TBI total dose: 1200-1420 cGy Recommended regimen:
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.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Percentage of Participants With Non-Relapse Mortality
Time Frame: Day 100, 1 Year, and 2 Years Post-transplant
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The events for non-relapse mortality are death due to any cause other than relapse of the underlying malignancy.
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Day 100, 1 Year, and 2 Years Post-transplant
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With Overall Survival
Time Frame: Six months, 1 Year, and 2 Years Post-transplant
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Overall survival is defined as the time from transplant to death from any cause.
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Six months, 1 Year, and 2 Years Post-transplant
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Percentage of Participants With Relapse/Progression
Time Frame: 1 Year Post-transplant
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Relapse/Progression is defined as relapse or progression of the primary malignancy.
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1 Year Post-transplant
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Primary Cause of Death
Time Frame: Up to 2 Years Post-transplant
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Up to 2 Years Post-transplant
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Disease Status
Time Frame: Day 100 Post-transplant
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Patients will be assessed for disease status at Day 100 post-HCT, classified as complete remission, partial remission, stable disease, and relapse/progressive disease.
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Day 100 Post-transplant
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Percentage of Participants Recovering Hematologic Function
Time Frame: Days 28 and 100 Post-transplant
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Recovery of hematologic function is described by the time to neutrophil and platelet recovery.
Time to neutrophil recovery will be the first of three consecutive days of > 500 neutrophils/μL following the expected nadir.
Time to platelet engraftment will be described by the date when platelet count is > 20,000/μL for the first of three consecutive labs with no platelet transfusions 7 days prior.
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Days 28 and 100 Post-transplant
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Chimerism
Time Frame: Week 4, Day 100, and 6 months Post-transplant
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Donor T-cell and myeloid chimerism will be described separately by conditioning regimen intensity (myeloablative or reduced intensity) according to proportions with mixed chimerism (5-95% donor cells out of all), full chimerism (>95% donor cells), or graft rejection (<5% donor cells).
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Week 4, Day 100, and 6 months Post-transplant
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Percentage of Participants With Acute Graft-Versus-Host Disease (GVHD)
Time Frame: Day 100 Post-transplant
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Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995: Skin stage: 0: No rash
Liver stage (based on bilirubin level)*: 0: <2 mg/dL 1.2-3 mg/dL 2.3.01-6 mg/dL 3.6.01-15.0 mg/dL 4.>15 mg/dL GI stage*: 0: No diarrhea or diarrhea <500 mL/day
GVHD grade: 0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4 |
Day 100 Post-transplant
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Percentage of Participants With Chronic Graft-Versus-Host Disease (GVHD)
Time Frame: 1 Year Post-transplant
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Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe.
Occurrence of chronic GVHD is defined as the occurrence of mild, moderate, or severe chronic GVHD per this classification.
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1 Year Post-transplant
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Infection Severity
Time Frame: 1 Year Post-transplant
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The maximum grade of infections reported by participants are described, as defined in the BMT CTN Technical MOP.
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1 Year Post-transplant
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Collaborators and Investigators
Publications and helpful links
General Publications
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Cyclophosphamide
- Melphalan
- Fludarabine
- Fludarabine phosphate
- Busulfan
- Vidarabine
Other Study ID Numbers
- BMTCTN0903
- U01HL069294 (U.S. NIH Grant/Contract)
- 5U24CA076518 (U.S. NIH Grant/Contract)
- BMT CTN 0903 (Other Identifier: Blood and Marrow Transplant Clinical Trials Network)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- Study Protocol
- Informed Consent Form (ICF)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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