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

NCT01640301 | Terminated Phase 1 Results DMC FDA Drug

• 5 other identifiers: 2498.00NCI-2011-033622498P01CA018029RG9212029
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (8)

• Anti-leukemic Potential Efficacy, in Terms of Duration of Response (Arm II)

  Response is assessed throughout the 1 year post treatment timeframe. Morphologic criteria for response: Complete Response (CR) = Bone Marrow blasts \<5%; no blasts with Auer rods; no extramedullary disease. Transfusion independent. Platelets ≥ 100,000/μl Absolute neutrophil count \>1000/μl (CRi: incomplete hematologic recovery CRp: incomplete platelet recovery) Partial Response (PR) = Decrease of at least 50% in the percentage of blasts to 5-25% in the bone marrow and the normalization of blood counts as for CR. (PRi and PRp if incomplete hematologic or platelet recovery) Stable Disease (SD) = Failure to achieve at least PR, but no evidence of progression for \>4 weeks.

  Up to 1 year

• Efficacy, in Terms of Relapse Rate (Arm I)

  At 1 year post-transplant

• Count of Participants Who Experienced Chronic Graft Versus Host Disease (GVHD) (Arm I)

  Up to 1 year

• Count of Participants Who Experienced Chronic Graft Versus Host Disease (GVHD) (Arm II)

  Up to 1 year

• Count of Participants Who Experienced Grade III-IV Acute Graft Versus Host Disease (GVHD) (Arm II)

  Up to 1 year following infusion per patient

• Count of Participants Who Experienced Grade III-IV Acute Graft-versus-host Disease (GVHD) (Arm I)

  Up to 1 year

• Treatment-related Toxicity Rate (Arm I)

  Outcome will be reported as a count of participants that experienced adverse events. Toxicity will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 4.0

  Up to 30 days after last study intervention per patient

• Treatment-related Toxicity Rate (Arm II)

  Outcome will be reported as a count of participants that experienced adverse events. Toxicity will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 4.0

  Up to 30 days after last study intervention per patient

Secondary Outcomes (5)

• Disease-free Survival After T Cell Therapy

  Up to 1 year

• Incidence of Relapse After T Cell Therapy (Arm II)

  Up to 1 year

• Maintenance of T Cell Receptor (TCR) Expression of Transduced T Cells (Arm I) i.e. Persistence

  Up to 28 days post intervention per patient

• Maintenance of Function of Transduced T Cells (Arm I)

  Up to 28 days post intervention per patient

• Time to Progression After T Cell Therapy (Arm I)

  Up to 1 year

Study Arms (2)

Arm I (high-risk for relapse after HCT)

EXPERIMENTAL

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.

Biological: Aldesleukin; Other: Laboratory Biomarker Analysis; Biological: WT1-Sensitized Allogeneic T-Lymphocytes

Arm II (relapsed after HCT)

EXPERIMENTAL

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.

Biological: Aldesleukin; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Biological: WT1-Sensitized Allogeneic T-Lymphocytes

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

Arm I (high-risk for relapse after HCT); Arm II (relapsed after HCT)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-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

Arm II (relapsed after HCT)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Arm II (relapsed after HCT)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (high-risk for relapse after HCT); Arm II (relapsed after HCT)

WT1-Sensitized Allogeneic T-Lymphocytes BIOLOGICAL

Given IV

Arm I (high-risk for relapse after HCT); Arm II (relapsed after HCT)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

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

Related Publications (2)

• 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.

  PMID: 31235963 DERIVED

• 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.

  PMID: 29042364 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

aldesleukin; Cyclophosphamide; fludarabine phosphate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Dr. Aude Chapuis
• Organization: Fred Hutchinson Cancer Research Center

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Program in Immunology

Study Record Dates

• First Submitted: November 29, 2011
• First Posted: July 13, 2012
• Study Start: December 6, 2012
• Primary Completion: March 20, 2020
• Study Completion: March 20, 2020
• Last Updated: July 14, 2022
• Results First Posted: June 23, 2022

Record last verified: 2022-06

Locations

US (1)