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

NCT ID: NCT01640301

Last Updated: 2022-07-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-06
• Study Completion Date: 2020-03-20

Brief Summary

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.

Detailed Description

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.

Conditions

Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Therapy-Related Acute Myeloid Leukemia; Donor; Hematopoietic Cell Transplant Recipient; HLA-A*0201 Positive Cells Present; Recurrent Acute Myeloid Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I (high-risk for relapse after HCT)

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

Group Type: EXPERIMENTAL

Aldesleukin

Intervention Type: BIOLOGICAL

Given SC

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

WT1-Sensitized Allogeneic T-Lymphocytes

Intervention Type: BIOLOGICAL

Given IV

Arm II (relapsed after HCT)

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.

Group Type: EXPERIMENTAL

Aldesleukin

Intervention Type: BIOLOGICAL

Given SC

Cyclophosphamide

Intervention Type: DRUG

Given IV

Fludarabine Phosphate

Intervention Type: DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

WT1-Sensitized Allogeneic T-Lymphocytes

Intervention Type: BIOLOGICAL

Given IV

Interventions

Aldesleukin

Given SC

Intervention Type: BIOLOGICAL

Cyclophosphamide

Given IV

Intervention Type: DRUG

Fludarabine Phosphate

Given IV

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

WT1-Sensitized Allogeneic T-Lymphocytes

Given IV

Intervention Type: BIOLOGICAL

Other Intervention Names

125-L-Serine-2-133-interleukin 2; Proleukin; r-serHuIL-2; Recombinant Human IL-2; Recombinant Human Interleukin-2; (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CTX; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Cytoxan; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; 2-F-ara-AMP; 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-; Beneflur; Fludara; SH T 586

Eligibility Criteria

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, as patients with lower weight would be incapable of providing high volume and frequent blood samples for monitoring and analysis
• 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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Aude Chapuis

Associate Professor, Program in Immunology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Aude Chapuis

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Countries

United States

References

Chapuis AG, Egan DN, Bar M, Schmitt TM, McAfee MS, Paulson KG, Voillet V, Gottardo R, Ragnarsson GB, Bleakley M, Yeung CC, Muhlhauser P, Nguyen HN, Kropp LA, Castelli L, Wagener F, Hunter D, Lindberg M, Cohen K, Seese A, McElrath MJ, Duerkopp N, Gooley TA, Greenberg PD. T cell receptor gene therapy targeting WT1 prevents acute myeloid leukemia relapse post-transplant. Nat Med. 2019 Jul;25(7):1064-1072. doi: 10.1038/s41591-019-0472-9. Epub 2019 Jun 24.

Reference Type: DERIVED

PMID: 31235963 (View on PubMed)

Oda SK, Daman AW, Garcia NM, Wagener F, Schmitt TM, Tan X, Chapuis AG, Greenberg PD. A CD200R-CD28 fusion protein appropriates an inhibitory signal to enhance T-cell function and therapy of murine leukemia. Blood. 2017 Nov 30;130(22):2410-2419. doi: 10.1182/blood-2017-04-777052. Epub 2017 Oct 17.

Reference Type: DERIVED

PMID: 29042364 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2011-03362

Identifier Type: REGISTRY

Identifier Source: secondary_id

2498

Identifier Type: -

Identifier Source: secondary_id

2498.00

Identifier Type: OTHER

Identifier Source: secondary_id

P01CA018029

Identifier Type: NIH

Identifier Source: secondary_id

View Link

RG9212029

Identifier Type: OTHER

Identifier Source: secondary_id

2498.00

Identifier Type: -

Identifier Source: org_study_id