Laboratory-Treated T Cells in Treating Patients With High-Risk Relapsed Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia Previously Treated With Donor Stem Cell Transplant



Status:Active, not recruiting
Conditions:Blood Cancer, Women's Studies, Hematology
Therapuetic Areas:Hematology, Oncology, Reproductive
Healthy:No
Age Range:Any
Updated:3/13/2019
Start Date:December 6, 2012
End Date:October 1, 2030

Use our guide to learn which trials are right for you!

Phase I/II Study of Adoptive Immunotherapy After Allogeneic HCT With Virus Specific CD8+ T Cells That Have Been Transduced to Express a WT1-Specific T Cell Receptor for Patients With Relapsed AML

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 acute myeloid leukemia (AML),
myelodysplastic syndrome (MDS), or chronic myelogenous leukemia (CML) that has returned after
a period of improvement (relapsed), 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.

PRIMARY OBJECTIVES:

I. Determine the safety and potential toxicities associated with treating patients with high
risk or relapsed AML, MDS, and CML after allogeneic hematopoietic cell transplantation (HCT)
by adoptive transfer of virus-specific cluster of differentiation (CD)8 T cells
genetically-modified to express a high affinity Wilms tumor 1 (WT1)-specific T cell receptor
(TCR).

II. Determine the anti-leukemic activity associated with treating patients with relapsed AML,
MDS and CML after allogeneic HCT by adoptive transfer of virus-specific CD8 T cells
genetically-modified to express a high affinity WT1-specific T cell receptor (TCR).

SECONDARY OBJECTIVES:

I. Determine the in vivo persistence of transferred T cells and ability to migrate to and
accumulate in bone marrow.

II. Determine the maintenance of TCR expression and function of transduced T cells.

OUTLINE: Patients are assigned to 1 of 2 treatment arms.

ARM I: Patients with no evidence of leukemia post-HCT receive WT1-sensitized T cells
intravenously (IV) over 45 minutes (or longer for patients who are 15-30 kg) on days 0 and 14
and aldesleukin subcutaneously (SC) twice daily (BID) on days 14-28.

ARM II: Patients with evidence of AML (minimal residual disease or overt relapse) post-HCT
receive cyclophosphamide IV and fludarabine phosphate IV daily on days -4 to -2. Patients
also receive WT1-sensitized T cells IV over 45 minutes (or longer for patients who are 15-30
kg) on days 0 and 21 and aldesleukin SC BID on days 14-28.

After completion of study treatment, patients are followed up weekly for 4 weeks, at weeks 6
and 8, at 3, 6, 12 months, and then annually for up to 15 years.

Inclusion Criteria:

- Patients must express HLA-A*0201

- Patients who are currently undergoing or who previously underwent matched allogeneic
HCT for:

- AML: Prospective enrollment will now be limited to patients with relapsed disease
(overt relapse or minimal residual disease) at any time post allogeneic HCT

- MDS will no longer be a criterion for eligibility

- CML will no longer be a criterion for eligibility

- 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 >= 15 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

Exclusion Criteria:

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

- In patients whose leukemic cells are available for evaluation, the expression of WT1
in the patient's bone marrow will be determined; if WT1 expression in the patient's
bone marrow is not highly expressed 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; testing for HIV should be within 6
months of enrollment

- 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 (B-hCG) pregnancy test result within
14 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 an unsuitable T cell donor

- DONOR: Unable to give informed consent
We found this trial at
1
site
Seattle, Washington 98109
Principal Investigator: Daniel Egan
Phone: 206-667-4971
?
mi
from
Seattle, WA
Click here to add this to my saved trials