Clinical Trial Detail

Clinical Trials

Clinical Trial Detail

Laboratory-Treated (Central Memory/Naive) CD8+ T Cells in Treating Patients With Newly Diagnosed or Relapsed Acute Myeloid Leukemia

Complete title: Phase I/II study of Autologous (Central Memory / Naïve) CD8+ T cells that have been Transduced to Express a WT1-specific T cell Receptor for Treatment of AML

Research Study Number 9296
 
Principal Investigator Daniel Egan
 
Phase I/II

Research Study Description

This phase I/II trial studies the side effects of laboratory-treated (central memory/naive) cluster of differentiation 8+ T cells (autologous Wilms tumor [WT]1-T cell receptor [TCRc]4 gene-transduced CD8-positive central memory T-cells [TCM]/naive T cells [TN] lymphocytes) and how well it works in treating patients with acute myeloid leukemia that is newly diagnosed or has come back. Genetically modified therapies, such as autologous WT1-TCRc4 gene-transduced CD8-positive TCM/TN lymphocytes, are taken from a patient's blood, modified in the laboratory so they specifically may kill cancer cells with a protein called WT1, and safely given back to the patient. The "genetically modified" T-cells have genes added in the laboratory to allow them to recognize leukemia cells that express WT1 and kill them.

Eligibility Criteria (must meet the following to participate in this study)

Ages Eligible for Study: Child, Adult, Senior

Sexes Eligible for Study: All

- Newly diagnosed (non-M3) AML patients

- Patients must be >= 15 kg

- Patients or parents/legal guardian must be able to give informed consent

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

- Elevated expression above of WT1 in pre-treatment bone marrow or peripheral blood by either of two methods:

-- * Increased expression of WT1 determined if the number of copies of WT1 divided by the number of copies of ABL x 10^4 is > 250 for bone marrow, or > 50 for peripheral blood;

-- * Demonstration of WT1 overexpression will be determined by immunohistochemical staining (IHC) in blasts as compared to adjacent normal myeloid and erythroid precursors, as determined by a Fred Hutchinson/Seattle Cancer Care Alliance pathologist

ELIGIBILITY FOR APHERESIS/BLOOD COLLECTION

- Human leukocyte antigen (HLA)-A*02:01 expression

- Elevated expression above of WT1 in bone marrow or peripheral blood: increased expression of WT1 will be determined if the number of copies of WT1 divided by the number of copies of ABL x 10^4 is > 250 for bone marrow, or > 50 for peripheral blood; or when available, demonstration of WT1 overexpression will be determined by immunohistochemical staining (IHC) in blasts as compared to adjacent normal myeloid and erythroid precursors, as determined by Fred Hutchinson/Seattle Cancer Care Alliance hematopathology

ELIGIBILITY FOR TREATMENT WITH TCRC4-TRANSDUCED CD8+ CELLS

- Response to therapy and completion of at least one cycle of consolidation therapy, and with disease status meeting one of the following criterion at the time of post-induction disease restaging:

-- * Minimal residual disease, as defined by detectable disease by flow cytometry but with marrow that is at least 10% cellular with < 5% blasts on morphologic review

-- * Complete remission with incomplete blood count recovery (Cri)/complete remission with incomplete platelet recovery (CRp), as defined by absence of detectable disease by flow cytometry, and marrow that is at least 10% cellular with < 5% blasts on morphologic review, but with neutrophil count < 1000/ul (Cri) and/or platelet count < 100,000/ul (CRp); in pediatric patients, a platelet threshold of < 80,000/ ul will be used, as per consensus pediatric response criteria

- Recovery from induction therapy (absolute neutrophil count [ANC] > 200/ul, platelet count > 20,000/ul)

- Continued CR, CRp, or Cri within 3 weeks of first dose WT-1 specific CD8+ T cells

- HLA-A*02:01 expression

- No plan for allogeneic stem cell transplantation within 3 months

- Elevated expression above baseline of WT1 in bone marrow or peripheral blood

- Additionally, patients treated in stage 1, cohort #3 must be EBV seropositive, given the inclusion of T cells derived from an EBV-specific subset in this group

ELIGIBILITY FOR OBSERVATION ARM

- Response to therapy and completion of at least one cycle of consolidation therapy, and with disease status meeting one of the following criterion

-- * Minimal residual disease, as defined by detectable disease by flow cytometry but with marrow that is at least 10% cellular with < 5% blasts on morphologic review

-- * Cri/CRp, as defined by absence of detectable disease by flow cytometry, and marrow that is at least 10% cellular with < 5% blasts on morphologic review, but with neutrophil count < 1000/ul and/or platelet count <100,000/ul. As previously stated, a platelet threshold of < 80,000/ul will be used to define CRp in pediatric patients, as per consensus pediatric response criteria

-- * Elevated expression above of WT1 in bone marrow or peripheral blood; (increased expression of WT1 will be determined if the number of copies of WT1 divided by the number of copies of ABL x 10^4 is > 250 for bone marrow, or > 50 for peripheral blood)

Other eligibility criteria may apply.

Exclusions (conditions that would prevent participation in this study)

- Active autoimmune disease (e.g. systemic lupus erythematosus, vasculitis, infiltrating lung disease, inflammatory bowel disease) in which possible progression during treatment would be considered unacceptable by the investigators

- Previous allogeneic hematopoietic cell transplant (HCT)

- Any condition or organ toxicity deemed by the principal investigator (PI) or the attending physician to place the patient at unacceptable risk for treatment on the protocol

- Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling or unable to use effective contraception or abstinence; women of childbearing potential must have a negative pregnancy test within two weeks prior to enrollment and initiation of treatment

- Clinically significant and ongoing immune suppression including, but not limited to: systemic immunosuppressive agents such as cyclosporine or corticosteroids (at an equivalent dose of 0.5 mg prednisone/kg per day, or higher), chronic lymphocytic leukemia (CLL), uncontrolled human immunodeficiency virus (HIV) infection

- Acute promyelocytic leukemia (M3 leukemia, per French-American-British classification)

EXCLUSION FOR TREATMENT WITH TCRC4-TRANSDUCED CD8+ CELLS

- Lack of HLA-A*02:01 expression

- Unable to generate antigen-specific WT1-specific CD8+ T cells for infusions; however, if a lower than planned number of cells is available, the patient will have the option to receive the generated WT1-specific T cells

- The expression of WT1 in the patient's peripheral blood and/or bone marrow will be determined; if WT1 expression in the patient specimen is within the normal physiologic range or is not detected, the patient will be ineligible for treatment with WT1-specific T cells (and will not be included in the observation cohort)

- Documented infections or oral temperature > 38.2 degree Celsius (C) fewer than 72 hours prior to receiving study treatment or systemic infection requiring chronic maintenance therapy; however, if these problems resolve, the start of treatment can be initiated on a delayed schedule

- Systemic steroids should be stopped 2 weeks before the start of treatment; topical and inhaled steroids are allowed

- Symptomatic and refractory central nervous system (CNS) leukemia

- Absolute neutrophil count (ANC) < 200/ul prior to treatment

- Platelets < 20,000/ul prior to treatment

- Ongoing >= grade 3 cardiac, pulmonary, renal, gastrointestinal or hepatic toxicities according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4 toxicity criteria

- Karnofsky performance status score (age >= 16 years) or Lansky play score (age < 16 years) =< 40%

- Medical or psychological conditions that, according to the PI, would make the patient unsuitable candidate for cell therapy

- Pregnancy or breast-feeding; women of childbearing potential must have a negative serum or urine beta-human chorionic gonadotropin (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

- Treatment with alemtuzumab or other T cell-depleting antibodies within 6 months of T cell therapy

Other exclusion criteria may apply.

Research Study Number 9296
 
Contact Seattle Cancer Care Alliance Intake Office
 
Telephone 800-804-8824 / 206-606-1024
 

Keywords: Leukemia, Acute Myeloid (AML); Hematologic Malignancies; Leukemia; Pediatric Cancers, Miscellaneous; Leukemia, Myeloid; Neoplasms; Hematologic Diseases

Disclaimer: We update this information regularly. However, what you read today may not be completely up to date.

Please remember:

  • Talk to your health care providers first before making decisions about your health care.
  • Whether you are eligible for a research study depends on many things. There are specific requirements to be in research studies. These requirements are different for each study.

Subscribe to an RSS feed of all trials