Donor Cellular Therapy After Cytarabine in Treating Patients With Intermediate-Risk Acute Myeloid Leukemia in Remission

PRIMARY OBJECTIVES:

I. To assess 2-year disease-free survival (as defined by time to death from any cause or
disease relapse, whichever is earlier) for patients < 60 years of age with intermediate-risk
acute myeloid leukemia (AML), in complete remission (CR) after induction chemotherapy, who
receive microtransplantation, compared to patients who received consolidation chemotherapy
only in a historical published comparable cohort of patients.

SECONDARY OBJECTIVES:

I. To obtain estimates of rate of relapse, treatment related mortality (TRM), all cause
mortality, in the microtransplantation (MST) group and compare it with allogeneic stem cell
group (historical cohort).

II. To obtain estimates of rate acute graft-versus-host disease (GVHD), chronic GVHD, time to
recovery of absolute neutrophil counts and platelets in patients with intermediate risk AML
receiving of chemotherapy in combination with microtransplantation.

TERTIARY OBJECTIVES:

I. Presence or absence of detectable donor chimerism post-microtransplantation until 6 months
after the last infusion.

II. Characteristics of the infused cells and composition of the graft. III. Dynamics of
T-cell clonality. IV. Immune cell subset analysis.

OUTLINE:

Approximately 4-6 weeks after completion of induction chemotherapy, patients receive
cytarabine intravenously (IV) over 1-3 hours twice daily (BID) on days -7 to -2 and
granulocyte colony stimulating factor (G-CSF) mobilized peripheral blood cells
(microtransplant) IV over 15-20 minutes on day 0. Treatment repeats every 8-10 weeks for 3
courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at least every 3 months for 2
years.

Inclusion Criteria:

- PATIENT INCLUSION CRITERIA:

- Acute myeloid leukemia-intermediate risk as defined by standard World Health
Organization (WHO) criteria for AML (at least 20% blasts in the peripheral blood or
bone marrow) at the time of initial diagnosis

- Diagnosis of AML according to WHO diagnostic criteria (at least 20% blasts in the
peripheral blood or bone marrow), with French-American-British (FAB)
classification other than M3 (acute promyelocytic leukemia), documented by bone
marrow aspiration and biopsy performed within 14 days prior to administration of
1st dose of remission induction chemotherapy

- Intermediate risk based on National Comprehensive Cancer Network (NCCN)

- In CR or complete remission with incomplete blood count recovery (CRi) after 1-2
induction chemotherapy documented by a bone marrow examination done within 2 weeks of
starting cytarabine in this protocol

- Must have achieved CR/CRi with less than 2 induction regimens that contain cytarabine
and anthracycline

- No 10/10 matched sibling donor available or not financially eligible for allogeneic
stem cell transplantation

- Must be within 3 months from the last induction regimen at the time of starting
cytarabine chemotherapy in this protocol

- Patient has at least one medically fit first- or second-degree family member expected
to be human leukocyte antigen (HLA) mismatched at 2-9/10 loci; in addition, the
prospective donor is willing to voluntarily donate hematopoietic stem cells and sign
consent forms

- Absolute neutrophil count (ANC) > 1500, unless due to direct bone marrow involvement
of disease

- Platelets > 75,000, unless due to direct bone marrow involvement of disease

- Hemoglobin > 8.0 gm/dL, transfusion allowed

- Serum creatinine < 2.0 x the upper limits of institutional normal (ULN)

- Total bilirubin < 1.5 x the upper limits of institutional normal

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 x the upper
limits of institutional normal (=< 5 x ULN for patients with suspected liver
involvement of leukemia)

- Cardiac left ventricular ejection fraction (LVEF) > 45%

- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2, and
estimated survival of at least 3 months

- Patients must be able to understand and agree to sign an Institutional Review Board
(IRB)-approved informed consent form

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control) prior to study entry, for the duration
of study, and for two months after study participation; should a woman become pregnant
or suspect she is pregnant while participating in this study, she should inform her
treating physician immediately

- DONOR INCLUSION CRITERIA:

- Donor screening; all donors will meet the standard blood donor criteria established by
the participating local blood center, American Association of Blood Banks (AABB)

- Donors will be selected from among the subject's relatives, adult children preferred

- Infectious disease testing will be done per Hemacare policy and AAAB guidelines

- Donor and intended recipient red cell type and compatibility will be determined

- Donors will be pre-selected on the basis of HLA haploidentity

- If patient is cytomegalovirus (CMV)-negative, donors who are CMV-negative will be
preferred; CMV serology of the donor will be tested prior to the allogeneic cell
donation; donations from CMV-positive donors to CMV-negative recipients will be given
if no CMV negative donor is available, and CMV surveillance and pre-emptive treatment
given as per guidelines below

Exclusion Criteria:

- PATIENT EXCLUSION CRITERIA:

- Acute promyelocytic leukemia

- High risk AML (see NCCN risk criteria)

- Low risk AML (see NCCN risk criteria)

- Fludarabine based therapy within 6 months of enrollment

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Who are pregnant and/or lactating

- Who have had non-biopsy surgery in the last 10 days

- Who have active central nervous system (CNS) disease; patients with previously treated
leptomeningeal disease without evidence of remaining leukemia cells by spinal fluid
will be eligible

- Patients with known active autoimmune disorder

- Patients known to be have active hepatitis B or C; (hepatitis B positive patients are
allowed if they are on appropriate antiviral agents such as lamivudine)

- Patients concurrently taking the following drugs are excluded: mycophenolate,
cyclosporine, prednisone > 20 mg/day, or immunosuppressive agents

- Researchers think that any life-threatening illness, condition or organ system
dysfunction can damage the safety of subjects

- Failure to demonstrate adequate compliance with medical therapy and follow-up

- DONOR EXCLUSION CRITERIA:

- Personal or family history of severe sickle cell disease or variant (unless donor has
tested negative); testing for the presence of hemoglobin S is not required

- Positive infectious disease test as dictated by blood collection center's standard
operating procedure (SOP)

- Current uncontrolled hypertension

- Pregnant or breast-feeding

- Currently taking lithium therapy

- History of autoimmune disease