A Pilot Trial of WT1 Peptide-Loaded Allogeneic Dendritic Cell Vaccine and Donor Lymphocyte Infusion for WT1-Expressing Hematologic Malignancies

- INCLUSION CRITERIA:

Inclusion Criteria:

Patient (i.e., transplant recipient)

Age greater than 1 year and less than 75 years.

One of the following WT1-expressing hematologic malignancies:

1. Acute lymphocytic leukemia (ALL), less than or equal to 25 percent marrow blasts.

2. Acute myelogenous leukemia (AML), less than or equal to 25 percent marrow blasts.

3. Chronic myelogenous leukemia (CML).

- Chronic phase, recurrent after or resistant to DLI or resistant to available abl
kinase inhibitors

- Accelerated phase, less than 20 percent marrow blasts

- Blastic phase, less than or equal to 25 percent marrow blasts

4. Myelodysplastic syndrome (MDS), less than 20 percent marrow blasts.

5. Non-Hodgkin's lymphoma (NHL), stage 4, less than or equal to 25 percent marrow
blasts.

6. Hodgkin's lymphoma (HL)

7. There will be no restriction on the volume of extramedullary disease, with the
exceptions of exclusions for central nervous system involvement or progression deemed
unacceptably rapid.

WT1 expression will be confirmed by at least one of the following criteria:

- Greater than 15 percent of malignant cells react with anti-WT1 by
immunohistochemistry.

- Positive quantitative RT-PCR of WT1 compared with a negative control.

HLA-A2 plus (heterozygous expression is acceptable).

Prior SCT: Prior HLA-matched (5-6/6 antigen or 8-10/10 allele) related or unrelated
allogeneic SCT required. Must be at least 42 days post-transplant, have had recovery
of transplant-associated toxicity to less than grade 2, and have post-transplant
donor engraftment as defined by donor chimerism greater than 50 percent (peripheral
blood), neutrophil recovery to an ANC greater than 500/microl independent of myeloid
growth factors, and platelet recovery to greater than 20,000/microL independent of
transfusion.

Disease status: Post-transplant residual or relapsed disease. Minimal residual
disease (MRD) by PCR or flow cytometry is acceptable in accordance with standard
disease-specific diagnostic criteria.

Availability of previous allogeneic donor to donate cells again.

Prior therapy: Disease-specific therapy must be stopped at least 14 days prior to
protocol Cycle 1 Day 1 (C1D1) and recovery of treatment-associated toxicity to
greater than grade 2 is required prior to initiation of protocol therapy. Patients
may have received prior DLI, but the last dose must be at least 28 days prior to C1D1
and there must be no active GVHD greater than grade 1 acute or extensive chronic.
Systemic immunosuppression must be stopped at least 28 days prior to protocol C1D1
and there must be no active GVHD greater than grade 1 acute or extensive chronic.
There is no time restriction in regard to prior intrathecal chemotherapy provided
there is complete recovery from any acute toxic effects of such. Patients receiving
hydroxyurea are allowed.

Performance status of 0, 1, 2, or 3.

Renal function: Patients must have a serum creatinine less than or equal to 1.5 times
the upper limit of normal based on age-specific normal range OR a creatinine
clearance greater than or equal to 60 mL/min/1.73 m(2).

Hepatic function: Patients must have a total bilirubin less than or equal to 2.0
mg/dl and ALT less than or equal to 5 times the upper limit of normal based on age-
specific normal ranges.

Ability to give informed consent. For patients less than 18 years of age, their legal
guardian must give informed consent. Pediatric patients will be included in age
appropriate discussion in order to obtain verbal assent.

Recipients of unrelated donor transplants must sign a release of information form to
authorize NMDP transfer of information to the NIH.

Subjects of childbearing or child-fathering potential must be willing to use a
medically acceptable form of birth control, which includes abstinence, while they are
being treated on this study.

Inclusion Criteria:

Donor

Weight greater than or equal to 18 kg, and for unrelated donors only age greater than
or equal to 18 years

Previous HLA-matched related or unrelated allogeneic donor. Donors must be 5-6/6
antigen or 8-10/10 allele matched.

HLA-A2 plus (heterozygous expression is acceptable).

Adequate venous access for peripheral apheresis, or consent to use a temporary
central venous catheter for apheresis.

Donor selection will be in accordance with NIH/CC Department of Transfusion Medicine
(DTM) criteria and, in the case of an unrelated donor, the National Marrow Donor
Program (NMDP) standards. When a potentially eligible recipient of an unrelated donor
product is identified, the recipient will complete an NMDP search transfer request to
allow NIH NMDP staff to contact the NMDP Coordinating Center, who will, in turn,
contact the donor's prior Donor Center. The NMDP Policy for Subsequent Donation
Requests will be followed and the appropriate forms (Subsequent Donation Request form
and Therapeutic T Cell Collection Prescription) will be submitted as required.

Ability to give informed consent. For donors less than 18 years of age, their legal
guardian must give informed consent. Pediatric donors must give verbal assent and be
cleared by social work and a mental health specialist to participate.

EXCLUSION CRITERIA:

Exclusion Criteria: Patient

Active GVHD greater than grade 1 acute or extensive chronic.

Breast feeding or pregnant females (due to risk to fetus or newborn).

Central nervous system (CNS) malignancy by any of the following criteria:

- Demonstration of malignant cells in the cerebrospinal fluid (CSF) in patients
with leukemia or MDS as manifested by CSF WBC greater than 5/microL and
confirmation of CSF blasts.

- Cranial neuropathies deemed secondary to the underlying malignancy.

- CNS mass lesions deemed secondary to the underlying malignancy.

- NB: History of CNS involvement without current evidence of CNS malignancy is NOT
an exclusion.

Rapidly progressive malignancy and/or clinically significant systemic illness (e.g.,
severe unstable infections or organ dysfunction) that in the judgment of the PI would
likely compromise the patient's ability to tolerate this therapy or interfere with
the study procedures, including but not limited to a life expectancy of less than 3
months.

High risk of inability to comply with protocol requirements as determined by
principal investigator, social work, and primary team.

HIV infection or HTLV-1 infection (due to associated immune suppression and decreased
likelihood of developing an immune response to the vaccine and increased risk of
severe infection).

Active hepatitis B or C infection as defined by seropositive for hepatitis B (HbSAg)
or hepatitis C and elevated liver transaminases.

Corticosteroids (dexamethasone equivalent up to 0.1 mg/kg/day) will be permitted.
Topical agents and/or inhaled corticosteroids are permitted.

Exclusion Criteria: Donor

History of medical illness that in the estimation of the PI or DTM/NMDP physician
poses prohibitive risk to donation.

Anemia (Hb less than 10 gm/dl) or thrombocytopenia (less than 100,000/microliter).

Breast feeding or pregnant females (due to risk to fetus or newborn).

High risk of inability to comply with protocol requirements as determined by the
principal investigator and donor center team.

Positive screening test for transfusion-transmissible infection in accordance with
DTM or NMDP donation standards.

Kaposi's sarcoma