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AzTrials

LeukemiaPhase 2NCT01410344

Allogeneic Transplant in HIV Patients (BMT CTN 0903)

A Phase 2 study testing Fludarabine and Busulfan, Fludarabine and Melphalan and Busulfan and Fludarabine in people with Leukemia and Lymphoma, run by Medical College of Wisconsin at 11 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 15 years and older
Conditions the study is for
Leukemia, Lymphoma, HIV
What is being tested?
Fludarabine and Busulfan, Fludarabine and Melphalan and Busulfan and Fludarabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
11 sitesUnited States
Study dates
Sep 2011to Jun 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 15 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.
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  • 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:
  • 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.
  • 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.
  • Renal: Creatinine clearance (calculated creatinine clearance is permitted) > 40 mL/min.
  • 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

Who cannot join

  • 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. .
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  • 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.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • Blood & Marrow Transplant Program at Northside Hospital

    Atlanta, Georgia, 30342

  • Johns Hopkins

    Baltimore, Maryland, 21231

  • City of Hope National Medical Center

    Duarte, California, 91010

  • University of Texas/MD Anderson CRC

    Houston, Texas, 77030

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53211

  • University of Pennsylvania Cancer Center

    Philadelphia, Pennsylvania, 19104

  • Mayo Clinic - Phoenix

    Phoenix, Arizona, 85054

  • Mayo Clinic - Rochester

    Rochester, Minnesota, 55905

  • Texas Transplant Institute

    San Antonio, Texas, 78229

  • University of CA, SF

    San Francisco, California, 94143-0324

  • H. Lee Moffitt Cancer Center

    Tampa, Florida, 33624

Other trials in United States

About this study

Official title: Allogeneic Hematopoietic Cell Transplant for Hematological Cancers and Myelodysplastic Syndromes in HIV-Infected Individuals (BMT CTN #0903)

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.

Read the detailed description

The study is designed to evaluate the feasibility and safety of reduced-intensity and fully-ablative allogeneic hematopoietic cell transplantation (HCT) for patients with hematological malignancies or myelodysplastic syndromes (MDS) who have HIV infection. The goal of the study is to assess the 100 day Non-relapse Mortality as well as immunological reconstitution in this patient population. Where feasible, an attempt will be made to identify human leukocyte antigen (HLA)-compatible hematopoietic stem cell donors who are homozygotes for the delta32 mutation of the chemokine receptor 5 (CCR5delta32). Patients will undergo a treatment plan review prior to registration on the trial. All patients will undergo allogeneic HCT from a matched sibling or unrelated donor.

Conditions
Leukemia, Lymphoma, HIV
Being tested
Fludarabine and Busulfan, Fludarabine and Melphalan, Busulfan and Fludarabine, Cyclophosphamide and Total Body Irradiation
Keywords
HIV, ALL, AML, MDS, Non-Hodgkin Lymphoma
Medical subject headings
Leukemia, Lymphoma, Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Fludarabine and BusulfanDrug

    Also called Fludara and Busulfex

    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.

  • Fludarabine and MelphalanDrug

    Also called Fludara and Alkeran

    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.

  • Busulfan and FludarabineDrug

    Also called Busulfex and Fludara

    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.

  • Cyclophosphamide and Total Body IrradiationDrug

    Also called Cytoxan® and radiation

    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.

Study groups in NCT01410344
Study groupRoleWhat they receive
Allogeneic TransplantOtherOne 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).
Receives: Drug: Fludarabine and Busulfan; Drug: Fludarabine and Melphalan; Drug: Busulfan and Fludarabine; Drug: Cyclophosphamide and Total Body Irradiation

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (9)

  1. Percentage of Participants With Overall Survival

    Overall survival is defined as the time from transplant to death from any cause.

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

  2. Percentage of Participants With Relapse/Progression

    Relapse/Progression is defined as relapse or progression of the primary malignancy.

    Measured: 1 Year Post-transplant

  3. Primary Cause of Death

    Measured: Up to 2 Years Post-transplant

  4. Disease Status

    Patients will be assessed for disease status at Day 100 post-HCT, classified as complete remission, partial remission, stable disease, and relapse/progressive disease.

    Measured: Day 100 Post-transplant

  5. Percentage of Participants Recovering Hematologic Function

    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.

    Measured: Days 28 and 100 Post-transplant

  6. Chimerism

    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).

    Measured: Week 4, Day 100, and 6 months Post-transplant

  7. Percentage of Participants With Acute Graft-Versus-Host Disease (GVHD)

    Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995:

    Skin stage:

    0: No rash

    1. Rash <25% of body surface area
    2. Rash on 25-50% of body surface area
    3. Rash on > 50% of body surface area
    4. Generalized erythroderma with bullous formation

    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

    1. Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD
    2. Diarrhea 1000-1499 mL/day
    3. Diarrhea >1500 mL/day
    4. Severe abdominal pain with or without ileus * If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1.

    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

    Measured: Day 100 Post-transplant

  8. Percentage of Participants With Chronic Graft-Versus-Host Disease (GVHD)

    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.

    Measured: 1 Year Post-transplant

  9. Infection Severity

    The maximum grade of infections reported by participants are described, as defined in the BMT CTN Technical MOP.

    Measured: 1 Year Post-transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Aug 2011 (estimated)
  2. Study startSep 2011
  3. Primary completionNov 2016
  4. Study completionJun 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01410344
Sponsor's protocol ID
BMTCTN0903
Other IDs
U01HL069294, BMT CTN 0903, 5U24CA076518
Status last verified
Dec 2022
First submitted
3 Aug 2011
Last updated
8 Dec 2022
Data monitoring committee
Yes
Individual data sharing
Yes: 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).

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.

    PubMed 28380315

  • 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.

    PubMed 31279752

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Fludarabine and Busulfan, Fludarabine and Melphalan and Busulfan and Fludarabine in people with Leukemia and Lymphoma, run by Medical College of Wisconsin at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 May 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Non-Relapse Mortality (time frame: Day 100, 1 Year, and 2 Years Post-transplant). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01410344, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Dec 2022.

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