Allogeneic Transplant in HIV Patients (BMT CTN 0903)

Overview

  • Study type

    Interventional
  • Study phase

    II
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Scottsdale/Phoenix, Arizona: 12-003862
    • Rochester, Minnesota: 12-003862
    NCT ID: NCT01410344
    Sponsor Protocol Number: BMT CTN 0903

About this study

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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

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 greater than or equal to 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 greater than or equal to 15 years of age.
  • Hematological malignancy associated with a poor prognosis with medical therapy alone. Diagnoses to be included:
    1. Patients with the diagnosis of Acute Myeloid or Lymphocytic Leukemia (AML or ALL) in first or second complete remission;
    2. Patients with advanced myelodysplastic syndromes (MDS), including those with International Prognostic Scoring System (IPSS) Int-2 and high-risk disease with less than 10 percent 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;
    3. Hodgkin Lymphoma beyond first remission achieving at least a partial response to most recent therapy with no evidence of progression prior to transplant;
    4. 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:
    1. 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;
    2. 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:
    1. Cardiac -Left ventricular ejection fraction at rest greater than or equal to 40 percent demonstrated by 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;
    2. Hepatic
      1. Total Bilirubin less than 2.0 mg/dL (except for isolated hyperbilirubinemia attributed to Gilbert syndrome or antiretroviral therapy as specified in the protocol Appendix E) and ALT and AST less than 5x the upper limit of normal;
      2. 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;
    3. Renal: Creatinine clearance (calculated creatinine clearance is permitted) greater than 40 mL/min;
    4. Pulmonary: DLCO, FEV1, FVC greater than or equal to 45 percent of predicted (corrected for hemoglobin).
  • Signed Informed Consent

Exclusion Criteria:

  • Karnofsky/Lansky performance score less than 70 percent.
  • Active CNS malignancy; however, patients with a history of positive 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 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 greater than 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. 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.

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Lisa Sproat, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Lisa Sproat, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

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CLS-20116804

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