An Early Phase 1 interventional study of Aldesleukin and Anti-thyroglobulin mTCR-transduced Autologous Peripheral Blood Lymphocytes in HLA-A2 Positive Cells Present, Metastatic Malignant Neoplasm and Metastatic Malignant Neoplasm in the Brain, sponsored by Albert Einstein College of Medicine. Terminated at 1 site in United States. Open to participants aged 18 Years to 66 Years. Per ClinicalTrials.gov, last updated 2023-08-04.
Sponsored by Albert Einstein College of Medicine · Early Phase 1, Interventional, and Treatment
This pilot clinical trial studies the side effects of anti-ESO (cancer/test antigen) murine T-cell receptor (mTCR)-transduced autologous peripheral blood lymphocytes and combination chemotherapy with cyclophosphamide and fludarabine phosphate in treating patients with cancer that has spread to other places in the body (metastatic) and expresses the gene NY-ESO-1. Donor white blood cells that are treated in the laboratory with anti-cluster of differentiation (CD)3 may help treat metastatic cancer. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine phosphate, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Aldesleukin may stimulate white blood cells, including natural killer cells, to kill metastatic cancer cells. Giving anti-ESO (cancer/test antigen) mTCR-transduced autologous peripheral blood lymphocytes together with combination chemotherapy and aldesleukin may kill more cancer cells.
PRIMARY OBJECTIVES:
I. To determine the safety and tolerability of the administration of anti-ESO (cancer/test antigen) mTCR (T cell receptor)-engineered peripheral blood lymphocytes (anti-thyroglobulin mTCR-transduced autologous peripheral blood lymphocytes) plus high-dose aldesleukin following a nonmyeloablative lymphoid depleting preparative regimen in human leukocyte antigen (HLA)-A2 positive patients with metastatic cancer expressing the ESO antigen.
SECONDARY OBJECTIVES:
I. Determine the in vivo survival of T-cell receptor (TCR) gene-engineered cells.
II. Determine the objective response rate by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
OUTLINE:
Patients receive standard cyclophosphamide intravenously (IV) over 1 hour on days -7 to -6 and fludarabine phosphate via intravenous piggy back (IVPB) over 30 minutes on days -5 to -1 followed by anti-ESO (cancer/test antigen) mTCR-transduced autologous peripheral blood lymphocytes IV over 20-30 minutes on day 0 and aldesleukin IV over 15 minutes approximately every 8 hours on days 0-4. Patients also receive filgrastim subcutaneously (SC) on days 1-4.
After completion of study treatment, patients are followed up at 6 weeks, annually for 5 years, and then periodically for 10 years thereafter.
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Serology:
Exclusion Criteria:
Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%; testing is required in patients with:
Pulmonary function testing in patients with:
Patients receive standard cyclophosphamide IV over 1 hour on days -7 to -6 and fludarabine phosphate via IVPB over 30 minutes on days -5 to -1 followed by anti-ESO (cancer/test antigen) mTCR-transduced autologous peripheral blood lymphocytes IV over 20-30 minutes on day 0 and aldesleukin IV over 15 minutes approximately every 8 hours on days 0-4. Patients also receive filgrastim SC on days 1-4.
Biological: Aldesleukin · Biological: Anti-thyroglobulin mTCR-transduced Autologous Peripheral Blood Lymphocytes · Drug: Cyclophosphamide · Biological: Filgrastim · Drug: Fludarabine Phosphate · Other: Laboratory Biomarker Analysis
Given IV
Also known as: 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2, Recombinant Human Interleukin-2
Given IV
Also known as: Anti-thyroglobulin mTCR-transduced Autologous PBL
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
Given SC
Also known as: Filgrastim XM02, G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, Tbo-filgrastim, Tevagrastim
Given IVPB
Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, Oforta, SH T 586
Correlative studies
Number of Participants With Toxicity Graded According to NCI-CTCAE Version 4.0
Toxicity graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0.
Time frame: Up to 15 years
Number of Participants Demonstrating in Vivo Survival of TCR Gene-engineered Cells
TCR and vector presence will be quantitated in PBMC samples (5-10mL) using established PCR techniques. This will provide data to estimate the in vivo survival of lymphocytes derived from the infused cells. In addition, measurement of CD4+ and CD8+ T-cells will be conducted and studies of these T-cell subsets in the circulation will be determined by using specific PCR assays capable of detecting the unique DNA sequence for each retroviral vector engineered T-cell. Descriptive statistics will be used to determine the in vivo survival of TCR gene-engineered cells.
Time frame: 6 weeks post evaluations scan and at 3, 6, and 12 months and annually thereafter
Number of Participants Demonstrating Objective Response Rate (Complete Response + Partial Response) Using RECIST Criteria
Objective Response Rate will be graded based on the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study Descriptive statistics will be used to determine the objective response rate.
Time frame: Up to 15 years
| Milestone | Treatment (mTCR, Aldesleukin) |
|---|---|
| Started | 3 |
| Completed | 2 |
| Not completed | 1 |
| Withdrew: Lost to follow-up | 1 |
Toxicity graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0.
| Participants | Treatment (mTCR, Aldesleukin) |
|---|---|
| Number of Participants With Toxicity Graded According to NCI-CTCAE Version 4.0 | 2 |
TCR and vector presence will be quantitated in PBMC samples (5-10mL) using established PCR techniques. This will provide data to estimate the in vivo survival of lymphocytes derived from the infused cells. In addition, measurement of CD4+ and CD8+ T-cells will be conducted and studies of these T-cell subsets in the circulation will be determined by using specific PCR assays capable of detecting the unique DNA sequence for each retroviral vector engineered T-cell. Descriptive statistics will be used to determine the in vivo survival of TCR gene-engineered cells.
No measurements were reported for this outcome.
Objective Response Rate will be graded based on the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study Descriptive statistics will be used to determine the objective response rate.
No measurements were reported for this outcome.
Collected over 9 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Treatment (mTCR, Aldesleukin) | 2/3 (66.7%) | 0/3 (0%) | 2/3 (66.7%) |
| Event | Treatment (mTCR, Aldesleukin) |
|---|---|
| HeadacheNervous system disorders | 2/3 |
| Weight GainInvestigations | 2/3 |
| VomitingGastrointestinal disorders | 2/3 |
| ChillsGeneral disorders | 2/3 |
| HypotensionVascular disorders | 2/3 |
| Neutrophil Count DecreasedInvestigations | 2/3 |
| Edema limbsGeneral disorders | 1/3 |
| DiarrheaGastrointestinal disorders | 1/3 |
| NauseaGastrointestinal disorders | 1/3 |
| ErythemaSkin and subcutaneous tissue disorders | 1/3 |
| Age, Categorical(Participants) | Treatment (mTCR, Aldesleukin) |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 3 |
| >=65 years | 0 |
| Sex: Female, Male(Participants) | Treatment (mTCR, Aldesleukin) |
|---|---|
| Female | 1 |
| Male | 2 |
| Race (NIH/OMB)(Participants) | Treatment (mTCR, Aldesleukin) |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 3 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
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Albert Einstein College of Medicine