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

NCT02770820 | Terminated Phase 1 Results DMC FDA Drug

• 5 other identifiers: 9296NCI-2016-00042P01CA018029P30CA015704RG9216011
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Myeloid Leukemia; EBV-Positive Neoplastic Cells Present; HLA-A*0201 Positive Cells Present; Blasts Under 5 Percent of Bone Marrow Nucleated Cells; Elevated WT1

Outcome Measures

Primary Outcomes (3)

• Number of Participants Who Experienced at Least One Serious Adverse Event (SAE)

  Evidence and nature of toxicities will be measured according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.This is the number of participants who experienced at least one adverse event (SAE).

  12 months after the last infusion

• Feasibility of Subsets

  Feasibility of generating TCR-transduced TN and TCM subsets for adoptive immunotherapy in a high-risk AML population. This is the proportion of subjects who sign the treatment consent, have a T cell product generated, and ultimately receive the study intervention.

  Up to 6 weeks

• Number of Participants Whose Treatment Resulted in TCRC4-transduced CD8+ Polyclonal TCM and TN Cell Persistence.

  Comparison of the relative frequencies and duration of persistence of adoptively transferred TCRC4-transduced CD8+ polyclonal TCM and TN cells, and of TCRC4-transduced TEBV CD8+ cells in blood and at the primary tumor site(s). This is the number of participants whose blood samples displayed TCRC4-transduced CD8+ polyclonal TCM and TN cell Persistence in follow up.

  12 months after the last infusion

Other Outcomes (4)

• Relative Maintenance

  Up to 15 years

• Patients With or Without Detectable MRD

  Up to 15 years

• Relative Frequencies at Primary Tumor Sites

  Up to 15 years

Study Arms (1)

Treatment (autologous CD8 T cells)

EXPERIMENTAL

Beginning 4 weeks after completion of last course of consolidation chemotherapy, patients receive autologous WT1-TCRc4 gene-transduced CD8+ TCM/TN lymphocytes IV over 1-4 hours on day 0 and again after a minimum of 3 weeks. Beginning 6 hours after the second infusion of T cells, patients also receive aldesleukin SC BID for 14 days in the absence of disease progression or unacceptable toxicity. Patients who have clinically benefitted from T cell therapy may receive additional infusions of T cells and aldesleukin at the discretion of the PI and the attending physician.

Biological: Aldesleukin; Biological: Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes; Other: Laboratory Biomarker Analysis

Interventions

Aldesleukin BIOLOGICAL

Given SC

Also known as: 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2, Recombinant Human Interleukin-2

Treatment (autologous CD8 T cells)

Autologous WT1-TCRc4 Gene-transduced CD8-positive Tcm/Tn Lymphocytes BIOLOGICAL

Given IV

Treatment (autologous CD8 T cells)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (autologous CD8 T cells)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with (non-M3) acute myeloid leukemia (AML)
• 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 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
• Demonstration of disease response to induction chemotherapy, in that patients must have achieve a morphologic remission (marrow that is at least 10% cellular with \< 5% blasts on morphologic review) after 1-2 induction cycles, regardless of minimal residual disease or incomplete hematologic recovery (CRi)/incomplete platelet recovery (CRp) status
• Determination of "high-risk" disease; subjects must meet one of the determinants of "high-risk disease", in terms of being at very high risk for relapse without allogeneic stem cell transplant, as per one of the follow criteria:
• A designation of "adverse" risk disease at the time of diagnosis, as defined by cytogenetic and molecular abnormalities specifically outlined in the 2017 European LeukemiaNet (ELN) guidelines for diagnosis and management of AML; these patients will meet "high-risk" designation, regardless of minimal residual disease or CRi/CRp status
• Relapsed leukemia; patients with cytogenetic or molecular classification other that adverse risk by ELN who go on to demonstrate disease relapse after a minimum duration of remission of 6 months, but who then attain a second complete remission with repeat induction chemotherapy; these patients will meet "high-risk" designation, regardless of minimal residual disease or CRi/CRp status
• Minimal residual disease, as defined by having detectable disease by one of the following criteria, but otherwise being in morphologic remission
• MRD by flow cytometry at any time after induction chemotherapy or during consolidation chemotherapy, when patients are otherwise classified as being in morphologic remission, and as defined by any abnormal myeloid blasts identified by flow cytometric analysis
• Cytogenetic MRD, as defined by a disease-specific abnormal karyotype at any point in patients who are otherwise in morphologic remission
• Molecular minimal residual disease (MRD) with one of the following markers, as specified below, in patients who are otherwise in morphologic remission:

You may not qualify if:

• 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 (untreated or detectable viral load within 3 months of enrollment)
• Acute promyelocytic leukemia (M3 leukemia, per French-American-British classification)
• 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
• 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
• If a patient meets other treatment eligibility but otherwise demonstrates delayed or poor recovery of peripheral blood counts to the above neutrophil and/or platelet thresholds, then treatment with the T cell intervention will be allowed if:
• Neutrophil and/or platelet counts remain below the thresholds after a period of at least 6 weeks from last systemic chemotherapy; OR neutrophil and/or platelet counts remain below the thresholds in the setting of a maintenance therapy, such as midostaurin; and
• The patient has detectable leukemia (e.g. flow cytometry positive or MRD by FISH or molecular testing); and
• The P.l. or treating physician documents that the likely cause of cytopenias is underlying disease as opposed to another cause (e.g. medication)

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

aldesleukin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Dr. Aude Chapuis
• Organization: FHCRC

achapuis@fredhutch.org

2066674369

Study Officials

• Aude Chapuis

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 25, 2016
• First Posted: May 12, 2016
• Study Start: November 6, 2017
• Primary Completion: June 1, 2020
• Study Completion: June 1, 2020
• Last Updated: October 29, 2021
• Results First Posted: June 23, 2021

Record last verified: 2021-08

Locations

US (1)