a phase i study of wt1 peptides to induce anti-leukemia immune responses following transplantation

Conditions: Acute Myelogenous Leukemia (AML); Chronic Myelogenous Leukemia (CML); Acute Lymphoblastic Leukemia (ALL); Myelodysplastic Syndrome (MDS); B Cell Malignancies

Summary: the purpose of this study is to determine the safety and effectiveness of administering wilms tumor gene 1 (wt1) cancer peptides. cancer peptides are short pieces of protein that are made in a laboratory to be like the peptides that can be found in cancer. these peptides are intended to be given as a "vaccine" to activate the immune cells in a person to attack his/her cancer. these peptides are mixed with an oily substance called montanide isa-51 and a white cell growth factor called granulocyte-macrophage colony-stimulating factor (gm-csf) which may help make the immune response stronger.

two subgroups with 2 dose cohorts of up to 6 patients each will be enrolled in this exploratory study in order to attempt to obtain immunologic and clinical data on patients with a variety of hematologic malignancies and amongst those in remission and early relapse. the 2 subgroups of patients will be treated with different schemas depending upon whether they are undergoing or have undergone autologous or allogeneic stem cell transplantation. for the autologous transplant patients: immune monitoring will require 90ml peripheral blood before the first immunization, 3-5 ml from the leukapheresis product, 40-90ml peripheral blood before the 4th immunization immunizations, after the last immunization (week 6-8), and at the discretion of the immune monitoring lab, every two months if immunizations are continued. for the allogeneic transplant patients: immune monitoring will require 90ml peripheral blood before the first immunization, 40-90ml peripheral blood before the 4th immunization immunizations, after the last immunization (week 6-8), and at the discretion of the immune monitoring lab, every two months if immunizations are continued. subjects will be monitored with blood pressure, temperature, and pulse, pre-injection, at 15 and 30 minutes after injection, prior to being allowed to leave the clinic. diphenhydramine 50 mg, solumedrol 100 mg, and epinephrine 1:1000 (1 ml) must be available bedside (or a clinic code cart must be available). if hypotension (sbp \ 110mmhg or \> 20 mmhg decrease for those with baseline sbp\ 101.5, acetaminophen 650 mg may be given orally.

Eligibility criteria:
inclusion criteria: there are two subgroups of patients: those undergoing autologous stem cell transplantation and those undergoing allogeneic stem cell transplantation. autologous transplant subgroup: -patients with the following hematologic malignancies (aml, cml, all, b cell malignancies, and myelodysplastic syndrome) who will be undergoing autologous stem cell transplantation. allogeneic transplantation subgroup: -patients with the following hematologic malignancies (aml, cml, all, b cell malignancies, and myelodysplastic syndrome) who have undergone allogeneic stem cell transplantation. there is no limitation on whether myeloablative or non-myeloablative chemotherapy is administered. a 3/6 or greater match is required for patients who have had an allogeneic stem cell transplant. both subgroups: * subject must be one of the following hla types: hla a2, a24, dr15 or drw53 (includes hla-dr4, -dr7, and drw9) * karnofsky performance status must be greater than or equal to 70%. * age ≥ 18 years. * ability to understand and provide signed informed consent that fulfills institutional review board guidelines. * patient must agree to use adequate contraception defined as: for women, one of the following (1) surgical sterilization, (2) approved hormonal contraceptives (such as birth control pills, depo-provera, or lupron depot), (3) barrier methods (such as a condom or diaphragm) used with a spermicide, or (4) an intrauterine device (iud); for men, one of the following: (1) surgical sterilization, or (2) a condom used with a spermicide. * in order to receive their immunizations, subjects should be: for autologous transplants: * at least 2 weeks from prior chemotherapy. * injections 1 and 2 must be completed prior to administration of any growth factor mobilization * injections 3, 4, 5, and 6, to resume 2 or more weeks from the time of their stem cell infusion if there has been no grade 3 or 4 non-hematologic, major organ toxicity within the preceding 1 week. non-major organ toxicities must have resolved to grade 2 or less. for allogeneic transplants, * at least 2 weeks from the time of their stem cell infusion. * without grade 3 or 4 non-hematologic major organ toxicity within the preceding 1 week; non major organ toxicities must have resolved to grade 2 or less. * we will require demonstration of \>50% donor myeloid hematopoiesis, based on microsatellite polymorphisms, prior to enrolling the patients with mds on the study. * adequate laboratory data as follows: hematologic function: wbc ≥ 3000/microliter, hemoglobin ≥ 9 g/dl (may transfuse or use erythropoietin to achieve this level), platelets ≥ 50,000/microliter ((may transfuse). renal and hepatic function: serum creatinine \< 1.5 mg/dl, bilirubin \< 1.5 mg/dl (except a bilirubin of \<2.0 will be permitted for patents with gilbert's syndrome), sgot/sgpt \< 2 x upper limit of normal. * subjects must have a cd4+ count is \> 200/mm. there is no specified requirement for cd8+ t cell count. * urine protein/creatinine ratio (upc) must be less than 1. exclusion criteria: * corticosteroid (greater than 10mg per day of prednisone or an equipotent dose of another corticosteroid) or other immunosuppressive therapy within the prior 1 week. * pregnant women and nursing mothers. * current or prior history of brain metastases. * more than 12 months since their stem cell transplant. * hiv +, hepatitis bsag +, hepatitis c ab+.

Keywords: autologous transplantation allogeneic transplantation