Clinical Trial Detail

This phase I/II trial studies the side effects of laboratory-treated T cells and to see how well they work in treating patients with high-risk relapsed acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelogenous leukemia (CML) previously treated with donor stem cell transplant. Biological therapies, such as cellular adoptive immunotherapy, may stimulate the immune system in different ways and stop cancer cells from growing. Placing a gene that has been created in the laboratory into a person's T cells may make the body build an immune response to kill cancer cells

Genders Eligible for Study: Both

- Patients must express human leukocyte antigen (HLA)-A*0201

- Patients undergoing matched allogeneic hematopoietic cell transplantation (HCT) for:

-- A) Acute Myeloid Leukemia (AML) including:

---- i) AML beyond first remission, therapy-related AML at any stage, primary refractory AML, AML in relapse (before or after HCT), AML with evidence of minimal residual disease (MRD) at time of HCT or after HCT (by multiparameter flow cytometry, cytogenetics, fluorescence in situ hybridization [FISH] or molecular studies); AML at any stage arising in a patient with an antecedent diagnosis of a hematologic disorder including myelodysplastic or myeloproliferative syndrome (e.g. chronic myelomonocytic leukemia, polycythemia vera, essential thrombocytosis, and agnogenic myeloid metaplasia with myelofibrosis)

---- ii) AML at any stage with unfavorable cytogenetic or molecular abnormalities: Monosomal karyotype (presence of two or more distinct autosomal chromosome monosomies or a single autosomal monosomy associated with at least one structural abnormality), del(5q)/-5, -7/del(7q), abn 3q, 9q, 11q, 20q, 21q, 17p, t(6;9), t(9;22), complex karyotype (>= 3 unrelated abnormalities), Inv(3) or t(3;3), t(6;11), +8 sole,+8 with 1 other abnormality other than t(8;21), t(9;11), inv (16), t(16;16), t(11;19), or normal cytogenetics with fms-related tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) mutation

-- B) Myelodysplastic syndrome (MDS) including:

---- i) Intermediate-2 or high risk category patients according to the International Prognostic Scoring System (IPSS >= 1.5) or poor risk karyotype defined as abnormalities involving chromosome 7 or complex karyotype (>= 3 unrelated abnormalities)

---- ii) Relapsed disease post HCT

-- C) Chronic Myeloid Leukemia (CML) including:

---- i) CML beyond chronic phase

---- ii) Relapsed disease post-HCT

- Patients who previously underwent allogeneic HCT for AML, MDS or CML and have experienced overt relapse or minimal residual disease at any time post-HCT can be offered enrollment on the protocol and may undergo therapy on Arm 2 of the protocol

- Patients must have an HLA-matched donor of hematopoietic stem cells (related or unrelated)

- Patients must be able to provide blood and bone marrow samples and undergo the procedures required for this protocol

- Patients must be >= 50 kg

- Patients must be able to give informed consent; parent or legal representative will be asked to consent for patients younger than 18 year old

- DONOR: Patient and donor (related or unrelated) must be HLA-matched and express HLA-A*0201

- DONOR: Donor must be Epstein-Barr virus (EBV) or cytomegalovirus (CMV) seropositive

- DONOR: Donor must be age 18 or older

- DONOR: In good general health

- DONOR: Able to give informed consent

Other eligibility criteria may apply.

- Central nervous system (CNS) tumor refractory to intrathecal chemotherapy and/or cranio-spinal radiation

- In patients whose leukemic cells are available for evaluation, expression of WT1 will be determined, and, if leukemic cells are negative for WT1 expression by polymerase chain reaction (PCR), the patient will be excluded from the study; patients with no evaluable leukemia will be eligible for enrollment based on the high frequency of positive leukemias (> 90%), and leukemia will be evaluated for WT1 expression if recurrence is detected

- Human immunodeficiency virus (HIV) seropositive

- Significant medical or psychological conditions that would make the patient unsuitable candidate for cell therapy at the discretion of the principal investigator (PI)

- Pregnancy or breast-feeding; women of childbearing potential must have a negative serum or urine beta-human chorionic gonadotropin (hCG) pregnancy test result within 7 days before the first dose of WT1-specific T cell infusion; woman of non-childbearing potential will be defined as being postmenopausal greater than one year or who have had a bilateral tubal ligation or hysterectomy; all recipients of WT1-specific T cells will be counseled to use effective birth control during participation in this study and for 12 months after the last T cell infusion

- DONOR: Less than 18 years old

- DONOR: Active infectious hepatitis

- DONOR: HIV or human T-lymphotropic virus (HTLV) seropositive

- DONOR: Pregnancy or nursing

- DONOR: Significant medical conditions (e.g. immunosuppressive therapy) that would make the donor unsuitable T cell donor

- DONOR: Unable to give informed consent

Other exclusion criteria may apply.