Allogeneic Transplant in HIV Patients (BMT CTN 0903)
Basic Trial Information
|Phase II||Biomarker/Laboratory analysis, Treatment||15 and over||BMTCTN0903|
NCI-2014-00311, 710, U01HL069294, 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 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.
Signed Informed Consent
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 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; 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 alanine aminotransferase (ALT)
and aspartate aminotransferase (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:
Diffusing capacity of the lung for carbon monoxide (DLCO), forced expiratory volume
in one second (FEV1), or forced vital capacity (FVC) greater than or equal to 45
percent of predicted (corrected for hemoglobin).
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).
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.
Patients must be greater than or equal to 15 years of age.
Patients must be willing to comply with effective Antiretroviral Therapy.
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 Clinical Laboratory Improvement Amendments (CLIA)
certification, or its equivalent, may be used to document infection.
Use of cord blood as the source of hematopoietic cells is not allowed.
T-cell depletion (including anti-thymocyte globulin (ATG) or alemtuzumab) is not
Patients with psychosocial conditions that would prevent study compliance and
follow-up, as determined by the principal investigator.
Prior allogeneic HCT.
Fertile men or women unwilling to use contraceptive techniques from the time of
initiation of mobilization until six-months post-transplant.
Pregnant (positive β-HCG) or breastfeeding.
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
AIDS related syndromes or symptoms that pose a perceived excessive risk for
transplantation-related morbidity as determined by the principal investigator.
Active Cytomegalovirus (CMV) retinitis or other CMV-related organ dysfunction.
Uncontrolled bacterial, viral or fungal infection (currently taking medication and
with progression or no clinical improvement).
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.
Karnofsky/Lansky performance score less than 70 percent.
Trial Contact Information
Trial Lead Organizations / Sponsors / Collaborators
Froedtert and the Medical College of Wisconsin
- Blood and Marrow Transplant Clinical Trials Network
- National Cancer Institute
- National Heart Lung and Blood Institute
Moffitt Cancer Center
Johns Hopkins University/Sidney Kimmel Cancer Center
Richard F. Ambinder
Siteman Cancer Center at Washington University
Ohio State University Comprehensive Cancer Center
M D Anderson Cancer Center
Uday R. Popat
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01410344
Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.