Autologous Transplant in HIV Patients (BMT CTN 0803)
Condition: Lymphoma; HIV
MeSH terms: Lymphoma
Intervention: Autologous transplant; BCNU; Etoposide; Cytarabine; Melphalan
Intervention description: Participants will receive the BEAM conditioning regimen followed by autologous HCT.; Participants will receive BCNU 300 mg/m^2 Day -6; Participants will receive Etoposide 100 mg/m^2 BID Days -5 to -2; Participants will receive Cytarabine 100 mg/m^2 BID Days -5 to -2; Participants will receive Melphalan 140 mg/m^2 Day -1
Intervention MeSH terms: Cytarabine; Etoposide; Melphalan; Carmustine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 43.0
Sex: All
Minimum age: 15 Years
Healthy volunteers: No
Keywords: HIV; B-cell Lymphoma; Burkitt's Lymphoma; Follicular Lymphoma; Hodgkin's Lymphoma

Summary:

      This study is a Phase II, multicenter trial assessing overall survival after autologous
      hematopoietic stem cell transplantation using a BEAM transplant regimen (carmustine,
      etoposide, cytarabine, melphalan) in lymphoma patients with HIV.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of persistent or recurrent World Health Organization (WHO) classification
             diffuse large B-cell lymphoma, composite lymphoma with > 50% diffuse large B-cell
             lymphoma, mediastinal B-cell lymphoma, immunoblastic, plasmablastic, Burkitt's or
             Burkitt-like or classical Hodgkin's lymphoma. Patients transformed from follicular
             lymphoma are eligible for the study, pending fulfillment of other criteria.

          -  15 years old or older

          -  Three or fewer prior regimens of chemotherapy over the entire course of their disease
             treatment (including one induction chemotherapy and no more than 2 salvage
             chemotherapies). Monoclonal antibody therapy and involved field radiation therapy will
             not be counted as prior therapies.

          -  All patients must have chemosensitive disease as demonstrated by at least a partial
             response to induction or salvage therapy.

          -  Less than or equal to 10% bone marrow involvement.

          -  Patients with adequate organ function as measured by: a)Cardiac: American Heart
             Association Class I: Patients with cardiac disease but without resulting limitation of
             physical activity. Ordinary physical activity does not cause undue fatigue,
             palpitation, dyspnea, or anginal pain. Additionally, all patients must have a left
             ventricular ejection fraction at rest greater than or equal to 40% demonstrated by
             Multi Gated Acquisition Scan (MUGA) or echocardiogram; b)Hepatic: (i) Bilirubin less
             than 2.0 mg/dL (except for isolated hyperbilirubinemia attributed to Gilbert syndrome
             or antiretroviral therapy) and alanine transaminase (ALT) and aspartate transaminase
             (AST) greater than 3x the upper limit of normal; (ii) Concomitant Hepatitis: Patients
             with chronic hepatitis B or C may be enrolled on the trial providing the above
             criteria are met. In addition, no active viral replication - undetectable (viral load
             less than 500 copies/ml) hepatitis B DNA level by PCR and no clinical or pathologic
             evidence of irreversible chronic liver disease; c)Renal: Creatinine clearance
             (calculated creatinine clearance is permitted) greater than 40 mL/min; d)Pulmonary:
             Carbon Monoxide Diffusing Capacity (DLCO), forced expiratory volume in 1 second
             (FEV1), forced vital capacity (FVC) greater than or equal to 45% of predicted
             (corrected for hemoglobin).

          -  Autologous peripheral stem cell graft with a minimum of greater than or less than 1.5
             x 10^6 CD 34+ cells/kg (target greater than or less than 2.0 x 10^6 CD 34+ cells/kg)
             or if peripheral blood stem cell (PBSC) mobilization fails, cells can be obtained by
             bone marrow harvest per institutional practices (in cases where bone marrow will be
             used for transplantation, the required CD34+ dose does not apply and institutional
             requirements for total nucleated cell dose should apply).

          -  Initiate conditioning therapy within 3 months of mobilization or bone marrow harvest.

          -  Signed informed consent.

          -  Patients on antiretroviral therapies (ARVs) can either have: a) Undetectable HIV viral
             load (VL less than 50 copies); b) If VL detectable at less than 2000 copies/mL must
             have review of previous antiretroviral regimens or previous genotypic or phenotypic
             testing which indicate the ability to fully suppress virus by addition of sensitive
             drugs. This review will be carried out by the Infectious Disease (ID) specialist
             caring for the patient; c)If VL detectable at greater than 2000 copies/mL, a current
             HIV genotype and/or phenotype must be obtained. If a HAART regimen to which the
             patient's virus is sensitive can be determined based on genotype and previous
             antiretroviral experience, then the patient will be considered eligible in this
             regard. This review will be carried out by the ID specialist caring for the patient.

        Exclusion Criteria:

          -  Karnofsky performance score less than 70%.

          -  Uncontrolled bacterial, viral or fungal infection (currently taking medication and
             with progression or no clinical improvement).

          -  Prior malignancy in the 5 years prior to enrollment except resected basal cell
             carcinoma, treated cervical carcinoma in situ or Kaposi's sarcoma: a)Symptomatic
             Kaposi's sarcoma currently requiring therapy is excluded (patients receiving topical
             therapy for minimal disease are not included in this definition); b)Prior treatment
             with topical agents, local radiation, or up to 6 cycles of cytotoxic chemotherapy at
             least six months prior is permitted; c) Other cancers treated with curative intent
             less than 5 years previously will not be allowed unless approved by the Medical
             Monitor or Protocol Chair; d)Cancer treated with curative intent more than 5 years
             previously will be allowed.

          -  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 autologous or allogeneic HCT.

          -  Patients with evidence of Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML)
             or abnormal cytogenetic analysis indicative of MDS on the pre-transplant bone marrow
             examination. Pathology report documentation need not be submitted.