Back to results

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

Primary Purpose

Recurrent Adult Acute Myeloid Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Secondary Acute Myeloid Leukemia

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Aldesleukin

Cyclophosphamide

Fludarabine Phosphate

Laboratory Biomarker Analysis

WT1-Sensitized Allogeneic T-Lymphocytes

About this trial

This is an interventional treatment trial for Recurrent Adult Acute Myeloid Leukemia

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Fred Hutch/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Arm I (high-risk for relapse after HCT)

Arm II (relapsed after HCT)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Efficacy, in Terms of Relapse Rate (Arm I)

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

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

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

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

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

Treatment-related Toxicity Rate (Arm II)

Secondary Outcome Measures

Disease-free Survival After T Cell Therapy

Incidence of Relapse After T Cell Therapy (Arm II)

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

Maintenance of Function of Transduced T Cells (Arm I)

Time to Progression After T Cell Therapy (Arm I)

Full Information

NCT ID

NCT01640301

First Posted

November 29, 2011

Last Updated

June 28, 2022

Sponsor

Fred Hutchinson Cancer Center

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01640301

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2022

Overall Recruitment Status

Terminated

Why Stopped

Terminated due to slow accrual.

Study Start Date

December 6, 2012 (Actual)

Primary Completion Date

March 20, 2020 (Actual)

Study Completion Date

March 20, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Fred Hutchinson Cancer Center

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

47 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm I (high-risk for relapse after HCT)

Arm Type

Experimental

Arm Description

Arm Title

Arm II (relapsed after HCT)

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Aldesleukin

Other Intervention Name(s)

125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2, Recombinant Human Interleukin-2

Intervention Description

Given SC

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

(-)-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

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Fludarabine Phosphate

Other Intervention Name(s)

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

Intervention Description

Given IV

Intervention Type

Other

Intervention Name(s)

Laboratory Biomarker Analysis

Intervention Description

Correlative studies

Intervention Type

Biological

Intervention Name(s)

WT1-Sensitized Allogeneic T-Lymphocytes

Intervention Description

Given IV

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Up to 1 year

Title

Efficacy, in Terms of Relapse Rate (Arm I)

Time Frame

At 1 year post-transplant

Title

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

Time Frame

Up to 1 year

Title

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

Time Frame

Up to 1 year

Title

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

Time Frame

Up to 1 year following infusion per patient

Title

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

Time Frame

Up to 1 year

Title

Treatment-related Toxicity Rate (Arm I)

Description

Time Frame

Up to 30 days after last study intervention per patient

Title

Treatment-related Toxicity Rate (Arm II)

Description

Time Frame

Up to 30 days after last study intervention per patient

Secondary Outcome Measure Information:

Title

Disease-free Survival After T Cell Therapy

Time Frame

Up to 1 year

Title

Incidence of Relapse After T Cell Therapy (Arm II)

Time Frame

Up to 1 year

Title

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

Time Frame

Up to 28 days post intervention per patient

Title

Maintenance of Function of Transduced T Cells (Arm I)

Time Frame

Up to 28 days post intervention per patient

Title

Time to Progression After T Cell Therapy (Arm I)

Time Frame

Up to 1 year

10. Eligibility

Sex

All

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Aude Chapuis

Organizational Affiliation

Fred Hutch/University of Washington Cancer Consortium

Official's Role

Principal Investigator

Facility Information:

Facility Name

Fred Hutch/University of Washington Cancer Consortium

City

Seattle

State/Province

Washington

ZIP/Postal Code

98109

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

31235963

Citation

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.

Results Reference

derived

PubMed Identifier

29042364

Citation

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.

Results Reference

derived

Learn more about this trial

We'll reach out to this number within 24 hrs