|Phase II||Biomarker/Laboratory analysis, Treatment||Active||15 and over||NCI, Other||710|
U01HL069294, BMT CTN 0903, NCT01410344
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.
Further Study Information
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 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.
- 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: a)Patients with the diagnosis of Acute Myeloid or Lymphocytic Leukemia (AML or ALL) in first or second complete remission; b)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; c)Hodgkin Lymphoma beyond first remission achieving at least a partial response to most recent therapy with no evidence of progression prior to transplant; d)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: a) 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; b) 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: a)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; bi)Hepatic - 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; bii)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) greater than 40 mL/min; d)Pulmonary: DLCO, FEV1, FVC greater than or equal to 45 percent of predicted (corrected for hemoglobin).
- Signed Informed Consent
- 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.
Trial Lead Organizations/Sponsors
Medical College of Wisconsin Cancer CenterNational Heart, Lung, and Blood Institute
National Cancer Institute
Blood and Marrow Transplant Clinical Trials Network
|Joseph Alvarnas||Study Chair|
|Richard Frederick Ambinder||Study Chair|
|Mary Horowitz, MD, MS|
|University of Florida Shands Cancer Center|
|John R Wingard, MD||Ph: 352-273-7760|
|H. Lee Moffitt Cancer Center and Research Institute at University of South Florida|
|Ernesto Ayala, MD||Ph: 813-745-1554|
|Hackensack University Medical Center Cancer Center|
|Scott Rowley, MD||Ph: 201-996-5828|
|Melissa Baker, MD|
|M. D. Anderson Cancer Center at University of Texas|
|Uday Popat, MD||Ph: 713-745-3055|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01410344
ClinicalTrials.gov processed this data on October 17, 2013
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