Allogeneic Transplant in HIV Patients (BMT CTN 0903)

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Basic Trial Information

PhaseTypeAgeTrial IDs
Phase IIBiomarker/Laboratory analysis, Treatment15 and overBMTCTN0903
NCI-2014-00311, 710, U01HL069294, NCT01410344

Trial Description

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. 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.

Eligibility Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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

allowed.

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

therapy.

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

Medical College of Wisconsin

  • Blood and Marrow Transplant Clinical Trials Network
  • National Cancer Institute
  • National Heart Lung and Blood Institute

Trial Sites

U.S.A.

Florida
Tampa

Moffitt Cancer Center

Ernesto Ayala
Principal Investigator

Maryland
Baltimore

Johns Hopkins University/Sidney Kimmel Cancer Center

Richard F. Ambinder
Principal Investigator

Missouri
Saint Louis

Siteman Cancer Center at Washington University

Peter Westervelt
Principal Investigator

Ohio
Columbus

Ohio State University Comprehensive Cancer Center

Sumithira Vasu
Principal Investigator

Texas
Houston

M D Anderson Cancer Center

Uday R. Popat
Principal Investigator

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.