Allogeneic Transplant in HIV Patients (BMT CTN 0903)
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ClinicalTrials.gov Identifier: NCT01410344 |
Recruitment Status
:
Active, not recruiting
First Posted
: August 5, 2011
Last Update Posted
: March 21, 2018
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Condition or disease | Intervention/treatment | Phase |
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Leukemia Lymphoma HIV | Drug: Fludarabine and Busulfan Drug: Fludarabine and Melphalan Drug: Busulfan and Fludarabine Drug: Cyclophosphamide and Total Body Irradiation | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 18 participants |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Allogeneic Hematopoietic Cell Transplant for Hematological Cancers and Myelodysplastic Syndromes in HIV-Infected Individuals (BMT CTN #0903) |
Actual Study Start Date : | September 2011 |
Estimated Primary Completion Date : | June 2018 |
Estimated Study Completion Date : | December 2018 |

Arm | Intervention/treatment |
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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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Drug: Fludarabine and Busulfan
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 Name: Fludara and Busulfex
Drug: Fludarabine and Melphalan
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 Name: Fludara and Alkeran
Drug: Busulfan and Fludarabine
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 Name: Busulfex and Fludara
Drug: Cyclophosphamide and Total Body Irradiation
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 Name: Cytoxan® and radiation
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- Non-Relapse Mortality [ Time Frame: 100 days ]The events for non-relapse mortality are death due to any cause other than relapse of the underlying malignancy
- Disease Status Following Transplant [ Time Frame: 100 days ]Patients will be assessed for disease status at Day 100 post-HCT: complete remission, partial remission (HL, NHL), stable disease (HL, NHL), relapse.
- Chimerism [ Time Frame: 4 weeks, 100 days and 6 months ]Blood samples will be evaluated for T cell and myeloid chimerism at 4 weeks, 100 days and 6 months post-transplant.
- Incidence of Infections [ Time Frame: Date of transplant through one year post-transplant ]Microbiologically documented infections will be reported by site of disease, date of onset, severity, and resolution, if any.
- Six Month Overall Survival [ Time Frame: Six months post transplant ]Overall survival is defined as time from transplant to death or last follow-up.
- Acute Graft-versus-Host Disease (GVHD) [ Time Frame: 100 Days ]Acute GVHD will be graded according to the BMT CTN Manual of Procedures. The time to onset of acute grades II-IV GVHD and grades III-IV GVHD will be recorded, as well as the maximum grade achieved.
- Chronic Graft-versus-Host Disease (GVHD) [ Time Frame: 100 days, 6 months, 2 years ]Chronic GVHD will be scored according to the BMT CTN Manual of Procedures. The time to onset of limited and extensive chronic GVHD will be recorded.
- Immunologic Reconstitution [ Time Frame: 8 Weeks; 6, 12 and 24 Months ]This will be measured in all patients at 8 weeks, 6 months, 12 months and 24 months post-transplant. Tests to be performed on peripheral blood at those time points include CD2, CD3, CD4, CD8, CD19, CD3+/CD25+, CD45 RA/RO, CD56+/CD3-, and quantitative immunoglobulins (IgM, IgG and IgA).
- Impact of Therapy on the HIV Reservoir [ Time Frame: Day 100, 6 Months, 12 Months, and 24 Months ]HIV-1 RNA in plasma will be measured by standard real-time reverse transcription polymerase chain reaction (RT-PCR) (detection limit 40 copies/ml) and by the investigational single copy assay (SCA, detection limit 0.38 copy/ml). HIV-1 DNA in peripheral blood mononuclear cells (PBMCs) and other cells will be quantified using the same primers and probes used for SCA but without a reverse transcription step. HIV-1 RNA levels will be measured in plasma prior to the initiation of ablative chemotherapy, and at Day +100, 1 and 2 years post-transplant.
- Hematologic Function [ Time Frame: Day 100, 6 months ]Hematologic function will be defined by absolute neutrophil count (ANC) greater than 1500, Hemoglobin greater than 10g/dL without transfusion support, and platelets greater than 100,000 and measured at Day 100 and 6 months. Use of growth factors will be noted.

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Ages Eligible for Study: | 15 Years and older (Child, Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.
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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.
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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).
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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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01410344
United States, Arizona | |
Mayo Clinic - Phoenix | |
Phoenix, Arizona, United States, 85054 | |
United States, California | |
City of Hope National Medical Center | |
Duarte, California, United States, 91010 | |
University of CA, SF | |
San Francisco, California, United States, 94143-0324 | |
United States, Florida | |
H. Lee Moffitt Cancer Center | |
Tampa, Florida, United States, 33624 | |
United States, Georgia | |
Blood & Marrow Transplant Program at Northside Hospital | |
Atlanta, Georgia, United States, 30342 | |
United States, Maryland | |
Johns Hopkins | |
Baltimore, Maryland, United States, 21231 | |
United States, Minnesota | |
Mayo Clinic - Rochester | |
Rochester, Minnesota, United States, 55905 | |
United States, Pennsylvania | |
University of Pennsylvania Cancer Center | |
Philadelphia, Pennsylvania, United States, 19104 | |
United States, Texas | |
University of Texas/MD Anderson CRC | |
Houston, Texas, United States, 77030 | |
Texas Transplant Institute | |
San Antonio, Texas, United States, 78229 | |
United States, Wisconsin | |
Medical College of Wisconsin | |
Milwaukee, Wisconsin, United States, 53211 |
Study Director: | Mary Horowitz, MD | Center for International Blood and Marrow Transplant Research |
Additional Information:
Publications of Results:
Responsible Party: | Medical College of Wisconsin |
ClinicalTrials.gov Identifier: | NCT01410344 History of Changes |
Other Study ID Numbers: |
BMTCTN0903 U01HL069294 ( U.S. NIH Grant/Contract ) BMT CTN 0903 ( Other Identifier: Blood and Marrow Transplant Clinical Trials Network ) 5U24CA076518 ( U.S. NIH Grant/Contract ) |
First Posted: | August 5, 2011 Key Record Dates |
Last Update Posted: | March 21, 2018 |
Last Verified: | March 2018 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | Results will be published in a manuscript and supporting information submitted to NIH BioLINCC (including data dictionaries, case report forms, data submission documentation, documentation for outcomes dataset, etc where indicated). |
Supporting Materials: |
Study Protocol Informed Consent Form (ICF) |
Time Frame: | Within 6 months of official study closure at participating sites. |
Access Criteria: | Available to the public |
URL: | https://biolincc.nhlbi.nih.gov/home/ |
Keywords provided by Medical College of Wisconsin:
HIV ALL AML MDS Non-Hodgkin Lymphoma |
Additional relevant MeSH terms:
Cyclophosphamide Fludarabine phosphate Melphalan Busulfan Fludarabine Vidarabine Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents |
Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antimetabolites, Antineoplastic Antimetabolites Antiviral Agents Anti-Infective Agents |