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
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| ClinicalTrials.gov Identifier: NCT01640301 |
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Recruitment Status :
Terminated
(Terminated due to slow accrual.)
First Posted : July 13, 2012
Results First Posted : June 23, 2022
Last Update Posted : July 14, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| 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 | Biological: Aldesleukin Drug: Cyclophosphamide Drug: Fludarabine Phosphate Other: Laboratory Biomarker Analysis Biological: WT1-Sensitized Allogeneic T-Lymphocytes | Phase 1 Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 47 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | December 6, 2012 |
| Actual Primary Completion Date : | March 20, 2020 |
| Actual Study Completion Date : | March 20, 2020 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: 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.
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Biological: Aldesleukin
Given SC
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Biological: WT1-Sensitized Allogeneic T-Lymphocytes Given IV |
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Experimental: 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.
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Biological: Aldesleukin
Given SC
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Fludarabine Phosphate Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Biological: WT1-Sensitized Allogeneic T-Lymphocytes Given IV |
- Anti-leukemic Potential Efficacy, in Terms of Duration of Response (Arm II) [ Time Frame: Up to 1 year ]
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) [ Time Frame: At 1 year post-transplant ]
- Count of Participants Who Experienced Chronic Graft Versus Host Disease (GVHD) (Arm I) [ Time Frame: Up to 1 year ]
- Count of Participants Who Experienced Chronic Graft Versus Host Disease (GVHD) (Arm II) [ Time Frame: Up to 1 year ]
- 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 ]
- Count of Participants Who Experienced Grade III-IV Acute Graft-versus-host Disease (GVHD) (Arm I) [ Time Frame: Up to 1 year ]
- Treatment-related Toxicity Rate (Arm I) [ Time Frame: Up to 30 days after last study intervention per patient ]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) [ Time Frame: Up to 30 days after last study intervention per patient ]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
- Disease-free Survival After T Cell Therapy [ Time Frame: Up to 1 year ]
- Incidence of Relapse After T Cell Therapy (Arm II) [ Time Frame: Up to 1 year ]
- 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 ]
- Maintenance of Function of Transduced T Cells (Arm I) [ Time Frame: Up to 28 days post intervention per patient ]
- Time to Progression After T Cell Therapy (Arm I) [ Time Frame: Up to 1 year ]
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| Ages Eligible for Study: | Child, Adult, Older Adult |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients must express HLA-A*0201
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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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01640301
| United States, Washington | |
| Fred Hutch/University of Washington Cancer Consortium | |
| Seattle, Washington, United States, 98109 | |
| Principal Investigator: | Aude Chapuis | Fred Hutch/University of Washington Cancer Consortium |
Documents provided by Aude Chapuis, Fred Hutchinson Cancer Center:
| Responsible Party: | Aude Chapuis, Associate Professor, Program in Immunology, Fred Hutchinson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT01640301 |
| Other Study ID Numbers: |
2498.00 NCI-2011-03362 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 2498 2498.00 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium ) P01CA018029 ( U.S. NIH Grant/Contract ) RG9212029 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium ) |
| First Posted: | July 13, 2012 Key Record Dates |
| Results First Posted: | June 23, 2022 |
| Last Update Posted: | July 14, 2022 |
| Last Verified: | June 2022 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Recurrence Neoplasms by Histologic Type Neoplasms Disease Attributes Pathologic Processes Aldesleukin Cyclophosphamide Fludarabine Fludarabine phosphate Interleukin-2 Immunosuppressive Agents Immunologic Factors |
Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antimetabolites, Antineoplastic Antimetabolites Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Anti-HIV Agents Anti-Retroviral Agents |