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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2018-01034 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| 2016-0400 | Other Identifier | M D Anderson Cancer Center |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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This phase I/Ib trial studies the side effects and best dose of utomilumab and how well it works with CD8-positive T-lymphocyte (T-cell infusion) and aldesleukin in treating patients with ovarian cancer that has come back. Aldesleukin may stimulate white blood cells to kill ovarian cancer cells. Giving white blood cells (T-cells) that have been activated by a vaccine with aldesleukin may kill more tumor cells. Immunotherapy with utomilumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving T-cell infusion with aldesleukin and utomilumab may work better in treating patients with ovarian cancer.
PRIMARY OBJECTIVES:
I. Assess the safety and toxicity of adoptively transferred central memory-type CTL targeting ovarian cancer antigens administered alone, and in combination with, utomilumab, an agonistic anti-CD137 antibody, in patients with platinum-resistant ovarian cancer.
II. Evaluate the functional and numeric in vivo persistence of adoptively transferred central memory-type CTL with and without utomilumab.
SECONDARY OBJECTIVES:
I. Evaluate the anti tumor effect of adoptively transferred central memory-type CTL targeting ovarian cancer antigens as measured by best overall response rate (BORR) and progression free survival (PFS).
OUTLINE: This is a dose escalation study of utomilumab.
Patients undergo leukapheresis. Patients then receive cyclophosphamide intravenously (IV) on day -2, CD8-positive T-lymphocyte via infusion on day 0, and aldesleukin subcutaneously (SC) every 12 hours for 14 days. Beginning 24 hours after CD8-positive T-lymphocyte, patients also receive utomilumab IV over 90 minutes on days 1, 29, 57, 85, 113, and 141 in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at days 3, 7, 14, 22, 28, 35, 43, 49, 56, 64, 70, 77, 84, 112, and 140.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (T-cell infusion, aldesleukin, utomilumab) | Experimental | Patients undergo leukapheresis. Patients then receive cyclophosphamide IV on day -2, CD8-positive T-lymphocyte via infusion on day 0, and aldesleukin SC every 12 hours for 14 days. Beginning 24 hours after CD8-positive T-lymphocyte, patients also receive utomilumab IV over 90 minutes on days 1, 29, 57, 85, 113, and 141 in the absence of disease progression or unacceptable toxicity. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Aldesleukin | Biological | Given IV |
|
| Measure | Description | Time Frame |
|---|---|---|
| Assess Safety and Toxicity of Adoptively Transferred Central Memory-type CTL Targeting Ovarian Cancer Antigens Administered Alone, and in Combination With, Utomilumab, an Agonistic Anti-CD137 Antibody, in Patients With Platinum Resistant Ovarian Cancer | Due to lack of funding, the study was not able to accrue a sample size large enough to address the primary and secondary objectives | will continue to be monitored on study with visits every 8 weeks or as often as clinically indicated unless the disease gets worse, participants starts another therapy, or the participants are taken off study |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluate the Anti Tumor Effect of Adoptively Transferred Central Memory-type CTL Targeting Ovarian Cancer Antigens as Measured by Best Overall Response Rate (BORR) and Progression Free Survival (PFS). | Due to lack of funding, the study was not able to accrue a sample size large enough to address the primary and secondary objectives | will continue to be monitored on study with visits every 8 weeks or as often as clinically indicated unless the disease gets worse, participants starts another therapy, or the participants are taken off study |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Amir A Jazaeri | M.D. Anderson Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| M D Anderson Cancer Center | Houston | Texas | 77030 | United States |
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| Label | URL |
|---|---|
| M D Anderson Cancer Center | View source |
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The study was activated on 07/16/2018 and the first participant was enrolled on 09/04/2018. The study was completd on 09/04/2020 when the last particiapnt treated was taken off study and the study was terminated on 12/20/2023. All screening and recruitment was done in a medical clinic setting.
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| ID | Title | Description |
|---|---|---|
| FG000 | Dose Level 1 | Cyclophosphamide (300 mg/m2) IV 2 days prior to infusion of T-Cells IV on Day 0 followed by IL-2 SC injections every 12 hours for 14 days |
| FG001 | Dose Level 2 | Cyclophosphamide (300 mg/m2) IV 2 days prior to infusion of T Cells IV on Day 0 followed by IL-2 SC injections every 12 hours for 14 days; low-dose anti-CD137 IV beginning on Day 1 and then every 4 weeks x6 doses |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 15, 2020 |
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| CD8-Positive T-Lymphocyte | Drug | Given IV |
|
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| Cyclophosphamide | Drug | Given IV |
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| Leukapheresis | Procedure | Undergo leukapheresis |
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| Utomilumab | Biological | Given IV |
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| FG002 | Dose Level 3 | Cyclophosphamide (300 mg/m2) IV 2 days prior to infusion of T Cells IV on Day 0 followed by IL-2 SC injections every 12 hours for 14 days; high-dose anti-CD137 IV beginning on Day 1 and then every 4 weeks x6 doses |
| COMPLETED |
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| NOT COMPLETED |
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Due to lack of funding, dose level 3 did not recruit any participants
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| ID | Title | Description |
|---|---|---|
| BG000 | Dose Level 1 | Cyclophosphamide (300 mg/m2) IV 2 days prior to infusion of T-Cells IV on Day 0 followed by IL-2 SC injections every 12 hours for 14 days |
| BG001 | Dose Level 2 | Cyclophosphamide (300 mg/m2) IV 2 days prior to infusion of T Cells IV on Day 0 followed by IL-2 SC injections every 12 hours for 14 days; low-dose anti-CD137 IV beginning on Day 1 and then every 4 weeks x6 doses |
| BG002 | Dose Level 3 | Cyclophosphamide (300 mg/m2) IV 2 days prior to infusion of T Cells IV on Day 0 followed by IL-2 SC injections every 12 hours for 14 days; high-dose anti-CD137 IV beginning on Day 1 and then every 4 weeks x6 doses |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Assess Safety and Toxicity of Adoptively Transferred Central Memory-type CTL Targeting Ovarian Cancer Antigens Administered Alone, and in Combination With, Utomilumab, an Agonistic Anti-CD137 Antibody, in Patients With Platinum Resistant Ovarian Cancer | Due to lack of funding, the study was not able to accrue a sample size large enough to address the primary and secondary objectives | Data were not collected due to lack of funding; the study was not able to accrue a sample size large enough to address the primary and secondary objectives | Posted | will continue to be monitored on study with visits every 8 weeks or as often as clinically indicated unless the disease gets worse, participants starts another therapy, or the participants are taken off study |
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| Secondary | Evaluate the Anti Tumor Effect of Adoptively Transferred Central Memory-type CTL Targeting Ovarian Cancer Antigens as Measured by Best Overall Response Rate (BORR) and Progression Free Survival (PFS). | Due to lack of funding, the study was not able to accrue a sample size large enough to address the primary and secondary objectives | Data were not collected due to lack of funding; the study was not able to accrue a sample size large enough to address the primary and secondary objectives | Posted | will continue to be monitored on study with visits every 8 weeks or as often as clinically indicated unless the disease gets worse, participants starts another therapy, or the participants are taken off study |
|
Through study completion, an average of 18 months
CTCAE V5.0
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dose Level 1 | Cyclophosphamide (300 mg/m2) IV 2 days prior to infusion of T-Cells IV on Day 0 followed by IL-2 SC injections every 12 hours for 14 days | 0 | 3 | 1 | 3 | 3 | 3 |
| EG001 | Dose Level 2 | Cyclophosphamide (300 mg/m2) IV 2 days prior to infusion of T Cells IV on Day 0 followed by IL-2 SC injections every 12 hours for 14 days; low-dose anti-CD137 IV beginning on Day 1 and then every 4 weeks x6 doses | 0 | 2 | 0 | 2 | 2 | 2 |
| EG002 | Dose Level 3 | Cyclophosphamide (300 mg/m2) IV 2 days prior to infusion of T Cells IV on Day 0 followed by IL-2 SC injections every 12 hours for 14 days; high-dose anti-CD137 IV beginning on Day 1 and then every 4 weeks x6 doses | 0 | 0 | 0 | 0 | 0 | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Syncope | Nervous system disorders | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal distension | Gastrointestinal disorders | Systematic Assessment |
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| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
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| Ascites | Gastrointestinal disorders | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Dizziness | Nervous system disorders | Systematic Assessment |
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| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Fatigue | General disorders | Systematic Assessment |
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| Hypotension | Vascular disorders | Systematic Assessment |
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| Neutrophil count increased | Investigations | Systematic Assessment |
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| Lymphocyte count decreased | Investigations | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Platelet count decreased | Investigations | Systematic Assessment |
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| Urine output decreased | Investigations | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | Systematic Assessment |
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| White blood cell decreased | Investigations | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Amir A. Jazaeri, MD | M D Anderson Cancer Center | 713-792-2921 | aajazaeri@mdanderson.org |
| Oct 10, 2024 |
| Prot_SAP_001.pdf |
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| ID | Term |
|---|---|
| D010051 | Ovarian Neoplasms |
| ID | Term |
|---|---|
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
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| ID | Term |
|---|---|
| C082598 | aldesleukin |
| C409469 | CD8 antigen, alpha chain |
| D016827 | CD8 Antigens |
| D003520 | Cyclophosphamide |
| D007937 | Leukapheresis |
| C577122 | utomilumab |
| ID | Term |
|---|---|
| D000945 | Antigens, Differentiation, T-Lymphocyte |
| D000943 | Antigens, Differentiation |
| D000954 | Antigens, Surface |
| D000941 | Antigens |
| D001685 | Biological Factors |
| D015415 | Biomarkers |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D016238 | Cytapheresis |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D001781 | Blood Component Removal |
| D047589 | Leukocyte Reduction Procedures |
| D002469 | Cell Separation |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D008919 | Investigative Techniques |
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| Between 18 and 65 years |
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| >=65 years |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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