Allogeneic Transplant in HIV Patients (BMT CTN 0903)

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.

Inclusion Criteria:

1. 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 ≥
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.

2. Patients must be willing to comply with effective Antiretroviral Therapy.

3. Patients must be ≥ 15 years of age.

4. 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% 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.

5. 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).

6. Patients with adequate organ function as measured by:

1. Cardiac: Left ventricular ejection fraction at rest ≥ 40% 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.

2. Hepatic:

i. Total Bilirubin < 2.0 mg/dL (except for isolated hyperbilirubinemia attributed to
Gilbert syndrome or antiretroviral therapy as specified in Appendix E) and alanine
aminotransferase (ALT) and aspartate aminotransferase (AST) < 5x the upper limit of
normal.

ii. 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) > 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) ≥ 45% of
predicted (corrected for hemoglobin).

7. Signed Informed Consent

Exclusion Criteria:

1. Karnofsky/Lansky performance score < 70%.

2. 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.

3. Uncontrolled bacterial, viral or fungal infection (currently taking medication and
with progression or no clinical improvement).

4. Active Cytomegalovirus (CMV) retinitis or other CMV-related organ dysfunction.

5. AIDS related syndromes or symptoms that pose a perceived excessive risk for
transplantation-related morbidity as determined by the principal investigator.

6. Untreatable HIV infection due to multidrug antiretroviral resistance. Patients with a
detectable viral load > 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 (described in Appendix D). This Review Committee will make the final
determination as to whether HIV viremia could potentially be suppressed with alternate
antiretroviral therapy. .

7. Pregnant (positive β-HCG) or breastfeeding.

8. Fertile men or women unwilling to use contraceptive techniques from the time of
initiation of mobilization until six-months post-transplant.

9. Prior allogeneic HCT.

10. Patients with psychosocial conditions that would prevent study compliance and
follow-up, as determined by the principal investigator.

11. T-cell depletion (including ATG or alemtuzumab) is not allowed.

12. Use of cord blood as the source of hematopoietic cells is not allowed.