A Phase I Dose Escalation Trial of WT1-Sensitized T Cells for Residual or Relapsed Leukemia After Allogeneic Hematopoietic Progenitor Cell Transplantation

Memorial Sloan Kettering Cancer Center1 site in 1 country22 target enrollmentFebruary 8, 2008

ConditionsLeukemia Myelodysplastic Syndrome

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Leukemia
Sponsor: Memorial Sloan Kettering Cancer Center
Enrollment: 22
Locations: 1
Primary Endpoint: assess toxicity of in vitro expanded allogeneic WT1 peptide-specific T-cells derived from transplant donor,when given to patients with leukemia or other WT1+ hematologic malignancy having relapsed after transplant or persistent minimal residual disease
Status: Completed
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This study will test the safety of giving you specialized white cells from your donor. They are called WT1 sensitized T cells. They have been grown in the lab and are immunized against a protein. The protein is called the Wilms' tumor protein, or WT1. Your leukemic cells make too much of this protein. We want to learn whether the WT1 sensitized T cells will attack the protein and kill the leukemia cells.

Registry

clinicaltrials.gov

Start Date

February 8, 2008

End Date

February 26, 2021

Last Updated

5 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Memorial Sloan Kettering Cancer Center

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Prior to receiving treatment, some patients may undergo diagnostic and/or other testing of their WT1 malignancies to determine if their disease is likely to respond to treatment with WT1 specific T cells. Alternatively, blood samples may be required for research tests to ascertain that the WT1-specific T-cells do not contain any cells that could react against the patient. These patients will sign a separate pre-treatment consent. If it is determined that a patient will qualify for and might benefit from infusions of WT1 CTLs, he/she will go on to sign the standard treatment consent for MSKCC IRB # 07-055 and be enrolled and treated on trial, if all other eligibility criteria are met.
•Patients eligible for this trial will include patients with a pathologically confirmed diagnosis of leukemia or myelodysplastic syndrome (MDS) who, following an allogeneic hematopoietic cell transplant, have relapsed with leukemia as demonstrated morphologically on peripheral blood smear or bone marrow aspirate, or have recurrent persistent minimal residual disease as demonstrated by at least 2 sequential testings separated by at least 1 week demonstrating molecular evidence of residual leukemia or MDS by FISH or cytogenetics. In addition, patients who are to receive an allogeneic hematopoietic cell transplant as treatment for a leukemia or myelodysplastic syndrome that has an expected of risk of relapse post transplant of \>30% will be eligible to have donor-derived WT1 peptide specific T cells generated prior to or at the time of transplant for immediate use post transplant at such time that the patient is found to have minimal residual disease or relapse. This includes patients with AML or ALL that is either refractory to primary induction therapy or is at any stage later than first relapse for AML or ALL, CML in a secondary chronic phase, accelerated disease or after treatment for blast crisis or RAEB or RAEBT stages of MDS which have not responded to or recurred following induction therapy. Furthermore, the patient's leukemic or MDS blasts should be documented to express the WT1 protein detectable by immunohistopathologic analysis of diagnostic paraffin embedded marrow biopsies, obtained at diagnosis of relapse or be of a type known to commonly express WT1 at high frequency. Expression of WT1 will be assessed by a modification of the technique of Dupont and Soslow (36) and graded according to an adaptation of the German Immunoreactive Score (IRS) which is the product of subscores for intensity of immunoreactivity (0-3+) and distribution of immunoreactivity (0-4+). For this study, leukemic blasts with IRS scores of 4-12 will be considered positive.
•A pathologically confirmed diagnosis of leukemia or MDS.
•Patients who have already received an allogeneic hematopoietic cell transplant and have either a documented relapse of leukemia or MDS or have recurrent persistent minimal residual disease as documented by at least 2 sequential testings, separated by 1 week, demonstrating molecular evidence of leukemia or MDS by FISH, cytogenetics or fluorescent immunocytometry.
•Patients who are to receive an allogeneic hematopoietic cell transplant as treatment for a leukemia or myelodysplastic syndrome that has an expected risk of relapse exceeding 30% will be eligible to have donor-derived WT1 peptide sensitized T cells generated prior to or at the time of transplant for immediate use post transplant at such time that the patient is found to have minimal residual disease or relapse. This includes patients with:
•ALL, AML or MDS refractory to primary induction therapy
•ALL or AML at any stage later than 1° relapse
•CML in 2° or greater chronic phase after chemotherapy
•CML in persistent accelerated phase or blast crisis
•High risk MDS (RAEB and RAEB+) which has failed to respond or has recurred following induction chemotherapy

Exclusion Criteria

•Patients with active (grade 2-4) acute graft vs. host disease (GVHD), chronic GVHD or an overt autoimmune disease (e.g. hemolytic anemia) requiring high doses of glucocorticosteroid (\>0.5 mg/kg/day prednisone or its equivalent) as treatment.
•Patients with other conditions not related to leukemic relapse (e.g. veno-occlusive disease or uncontrolled bacterial, viral or invasive fungal infection) which are also life-threatening and which would preclude evaluation of the effects of a T cell infusion.
•Patients who are pregnant.
•Donor Eligibility for Donation of Blood Lymphocytes for Generation of Donor-Derived WT-1-Specific T Cells.
•The eligibility criteria for the donor of blood to be used to generate WT1 peptide sensitized T cells are:
•The donor of WT-1 specific T. lymphocytes will be the same donor who provided the patient's hematopoietic stem cell transplant (HSCT). These normal donors will be evaluated for evidence of prior sensitization to EBV by EBV serology. If the donor is seropositive, and donor T cells are sensitized with the donor's WT-1 peptide- loaded EBV transformed B cells, EBV-specific T-cells will also be generated from seropositive donors generating WT-1 specific T-cells, and their growth and persistence post transfer will be compared to that of the WT 1 specific T-cells.
•Since the donor will have already undergone an extensive evaluation of his/her health to ascertain eligibility for donating the patient's HSCT, re-evaluation for this blood donation will be limited to a clinical history, physical examination and blood tests to insure against any new condition which, in the opinion of the donor's physician, preclude the donor from donating the blood required.
•New health conditions which would exclude a transplant donor from a second blood donation are limited, but include:
•New onset of an HIV infection
•Other uncontrolled infection which could be transmitted to the patient by blood cells and would place the patient at significant increased risk of severe morbidity or death.

Outcomes

Primary Outcomes

assess toxicity of in vitro expanded allogeneic WT1 peptide-specific T-cells derived from transplant donor,when given to patients with leukemia or other WT1+ hematologic malignancy having relapsed after transplant or persistent minimal residual disease

Time Frame: conclusion of the study

Secondary Outcomes

to assess the effects of the adoptively transferred T cells on the progression of disease(conclusion of the study)
to quantitate the number of WT1 peptide-specific T cells in the blood at defined intervals post infusion in order to determine their survival and proliferation in the host.(conclusion of the study)