Microtransplantation to Treat Refractory or Relapsed Hematologic Malignancies in Younger Patients

PRIMARY OBJECTIVES:

- To assess the safety and feasibility of standard chemotherapy plus GCSF-mobilized
Hematopoietic Progenitor Cell, Apheresis (HPC-A) in pediatric patients with relapsed or
refractory hematologic malignancies.

- To estimate the response rates to standard chemotherapy plus GCSF-mobilized HPC-A in
pediatric patients with relapsed or refractory hematologic malignancies.

SECONDARY OBJECTIVES:

- To describe the event-free and overall survival of patients treated with standard
chemotherapy plus GCSF-mobilized HPC-A.

- To estimate the time to neutrophil and platelet recovery after treatment with standard
chemotherapy plus GCSF-mobilized HPC-A.

- To determine the cumulative incidence of acute and chronic graft-versus-host disease
(GVHD).

OTHER PRESPECIFIED OBJECTIVES:

- To characterize donor chimerism and microchimerism.

Patients will receive standard chemotherapy followed by infusion of donor peripheral blood
mononuclear cells 2 days after the completion of chemotherapy. Patients who have at least a
partial response are eligible to receive a second cycle.

Diagnostic lumbar puncture and intrathecal (IT) chemotherapy will be given prior to cycle 1.
Patients without evidence of central nervous system (CNS) leukemia will receive no further IT
therapy during cycle 1. Patients with CNS disease will receive weekly IT therapy
(age-adjusted methotrexate, hydrocortisone, and cytarabine) until the cerebrospinal fluid
(CSF) becomes free of leukemia (minimum of 4 doses).

Bone marrow aspiration (BMA) and biopsy to assess response will be performed on approximately
day 29 of therapy.

For hematopoietic stem cell mobilization, donors will receive G-CSF (Filgrastim) (Neupogen®)
each day for 5 days given subcutaneously (SQ) prior to HPC-A collected by leukapheresis on
day 6.

INCLUSION CRITERIA - AML and MDS PARTICIPANTS

- Participants must have a diagnosis of AML or myelodysplastic syndrome (MDS), ALL, and
must have disease that has relapsed or is refractory to chemotherapy, or that has
relapsed after HSCT.

- Refractory disease is defined as persistent disease after at least two courses of
induction chemotherapy.

- Patients with AML must have ≥ 5% leukemic blasts in the bone marrow or have
converted from negative minimal residual disease (MRD) status to positive MRD
status in the bone marrow as assessed by flow cytometry. If an adequate bone
marrow sample cannot be obtained, patients may be enrolled if there is
unequivocal evidence of leukemia in the peripheral blood.

- Participant is ≤ 21 years of age (i.e., has not reached 22nd birthday).

- Adequate organ function defined as the following:

- Total bilirubin ≤ upper limit of normal (ULN) for age, or if total bilirubin is >
ULN, direct bilirubin is ≤ 1.5 mg/dL

- AST (SGOT)/ALT (SGPT) < 5 x ULN

- Calculated creatinine clearance > 50 ml/min/1.73m^2 as calculated by the Schwartz
formula for estimated glomerular filtration rate >

- Left ventricular ejection fraction ≥ 40% or shortening fraction ≥ 25%.

- Has an available HPC-A donor.

- Performance status: Lansky ≥ 50 for patients who are ≤ 16 years old and Karnofsky ≥
50% for patients who are > 16 years old.

- Does not have an uncontrolled infection requiring parenteral antibiotics, antivirals,
or antifungals within one week prior to first dose. Infections controlled on
concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per
institutional guidelines is acceptable.

- Patient has fully recovered from the acute effects of all prior therapy and must meet
the following criteria.

- At least 14 days must have elapsed since the completion of myelosuppressive
therapy.

- At least 24 hours must have elapsed since the completion of hydroxyurea, low-dose
cytarabine (up to 200 mg/m^2/day), and intrathecal chemotherapy.

- At least 30 days must have elapsed since the use of investigational agents.

- For patients who have received prior HSCT, there can be no evidence of GVHD and
greater than 60 days must have elapsed since the HSCT. Patients cannot be
receiving therapy, including steroids, for GVHD.

- Post-menarchal female has had negative serum pregnancy test within 7 days prior to
enrollment.

- Male or female of reproductive potential has agreed to use effective contraception for
the duration of study participation.

- Not breastfeeding

INCLUSION CRITERIA - HPC-A CELL DONOR

- At least 18 years of age.

- Family member (first degree relatives).

- Not pregnant as confirmed by negative serum or urine pregnancy test within 7 days
prior to enrollment (if female).

- Not breast feeding.

- Meets donation eligibility requirements as outlined by 21 CFR 1271.