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| ID | Type | Description | Link |
|---|---|---|---|
| 14-C-0022 |
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Background:
Objectives:
- To determine if there is a difference in the rate of response between patients who have received prior anti-PD1 and those who have not.
Eligibility:
- Individuals at least 18 years and less than or equal to 70 years of age who have metastatic melanoma.
Design:
Background:
Objectives:
Eligibility:
Design:
Not provided
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1N -Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin | Experimental | Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen in participants without prior treatment pembrolizumab or nivolumab Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) Young TIL: Day 0: Cells will be infused intravenously (IV) |
|
| Arm 1P - Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin | Experimental | Standard Chemo Prep Regimen Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen in participants previously treated with pembrolizumab or nivolumab. Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) Young TIL: Day 0: Cells will be infused intravenously (IV) |
|
| Arm 2/Foll By Arm 1P-Low dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin | Experimental | Decreased Chemo Prep Regimen+Retreat. Young TIL+High Dose Interleukin-2, Decreased Chemo Preparative Regimen. Young TIL+High Dose Interleukin-2, Standard Chemo (Retreat). Lower dose preparative regimen + Young TIL Cells. Aldesleukin: 720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 30 mg/kg/day intravenous piggy-back (IVPB) daily for 3 days. Cyclophosphamide: Days -5 to -3 (low-dose arm): Cyclophosphamide 300 mg/m^2 IV over 60 minutes. Young TIL: Day 0: Cells will be infused IV. Retreatment: Standard Chemo Prep Regimen. Aldesleukin: 720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days. Cyclophosphamide: 60 mg/kg/day X 2 days IV. Young TIL: Day 0: Cells will be infused IV. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Aldesleukin | Drug | 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Number of participants with Grades 3-5 treatment-related adverse events were compared in Arm 1N and Arm 1P; and adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 3 is severe. Grade 4 is life-threatening, and Grade 5 is death related to adverse event. | 30 days after end of treatment |
| Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | Clinical response to treatment was assessed by the Response Evaluation Criteria In Solid Tumors (RECIST v1.0). Complete Response (CR) is disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Progressive Disease (PD) is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD. | 4 weeks after cell infusion, then every 3 months x 3 and then every 6 months for 5 years, then per Principal Investigator (PI) discretion up to 5 years or disease progression |
| Overall Response Rate (ORR) | Overall response is the best response recorded from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.0). Progression is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | Date of cells until time of disease progression, up to approximately 67.2 months. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Treatment-related Adverse Events for Participants Who Received Pembrolizumab | Number of treatment-related adverse events for participants who received pembrolizumab. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. | Date treatment consent signed until approximately 4 weeks following last dose of Pembrolizumab, up to 4 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) | Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. |
-INCLUSION CRITERIA:
Measurable metastatic melanoma with at least one lesion that is resectable for tumor infiltrating lymphocytes (TIL) generation and at least one other lesion that can be measured by Response Evaluation Criteria In Solid Tumors (RECIST) criteria.
Confirmation of diagnosis of metastatic melanoma by the Laboratory of Pathology of National Cancer Institute (NCI).
Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible.
Greater than or equal to 18 years of age and less than or equal to 70 years of age.
Ability of subject to understand and the willingness to sign the Informed Consent Document
Willing to sign a durable power of attorney.
Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2.
Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to four months after treatment.
Serology:
Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus.
Hematology:
Chemistry:
More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo). Patients must have progressive disease after prior treatment.
Note: Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less.
Subjects must be co-enrolled in 03-C-0277
EXCLUSION CRITERIA:
Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
Active systemic infections, (e.g.: requiring anti-infective treatment), coagulation disorders or any other active major medical illnesses.
Concurrent systemic steroid therapy.
History of severe immediate hypersensitivity reaction to any of the agents used in this study.
History of coronary revascularization or ischemic symptoms.
Any patient known to have an left ventricular ejection fraction (LVEF) less than or equal to 45%
Documented LVEF of less than or equal to 45%, note: testing is required in patients with:
Patients who are receiving other investigational agents
Documented forced expiratory volume (FEV1) less than or equal to 60% predicted tested in patients with:
Not provided
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| Name | Affiliation | Role |
|---|---|---|
| Stephanie L Goff, M.D. | National Cancer Institute (NCI) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland | 20892 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18809613 | Background | Dudley ME, Yang JC, Sherry R, Hughes MS, Royal R, Kammula U, Robbins PF, Huang J, Citrin DE, Leitman SF, Wunderlich J, Restifo NP, Thomasian A, Downey SG, Smith FO, Klapper J, Morton K, Laurencot C, White DE, Rosenberg SA. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol. 2008 Nov 10;26(32):5233-9. doi: 10.1200/JCO.2008.16.5449. Epub 2008 Sep 22. | |
| 11230486 |
| Label | URL |
|---|---|
| NIH Clinical Center Detailed Web Page | View source |
Not provided
All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.
Clinical data will be available during the study and indefinitely.
Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the Study Principal Investigator (PI).
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm 1N -Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin | Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen in participants without prior treatment pembrolizumab or nivolumab Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) Young TIL: Day 0: Cells will be infused intravenously (IV) |
| FG001 | Arm 1P - Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin | Standard Chemo Prep Regimen Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen in participants previously treated with pembrolizumab or nivolumab. Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) Young TIL: Day 0: Cells will be infused intravenously (IV) |
| FG002 | Arm 2/Foll By Arm 1P-Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin | Decreased Chemo Prep Regimen+Retreat. Young TIL+High Dose Interleukin-2, Decreased Chemo Preparative Regimen. Young TIL+High Dose Interleukin-2, Standard Chemo (Retreat). Lower dose preparative regimen + Young TIL Cells. Aldesleukin: 720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 30 mg/kg/day intravenous piggy-back (IVPB) daily for 3 days. Cyclophosphamide: Days -5 to -3 (low-dose arm): Cyclophosphamide 300 mg/m^2 IV over 60 minutes. Young TIL: Day 0: Cells will be infused IV. Retreatment: Standard Chemo Prep Regimen. Aldesleukin: 720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days. Cyclophosphamide: 60 mg/kg/day X 2 days IV. Young TIL: Day 0: Cells will be infused IV. |
| FG003 | Arm 2- Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin | Decreased Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2 Lower Dose preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 30 mg/kg/day intravenous piggy-back (IVPB) daily for 3 days Cyclophosphamide: Days -5 to -3 (low-dose arm): Cyclophosphamide 30 mg/kg IV over 60 minutes for 2 days. Young TIL: Day 0: Cells will be infused intravenously (IV) |
| FG004 | Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin | Standard Chemo Prep Regimen(SCPR)+Retreat. Young TIL+High Dose(HD) Interleukin-2, SCPR. Young TIL+HD Interleukin-2, SC(Retreat). SCPR+Young TIL Cells retreatment with SCPR+Young TIL Cells+pembrolizumab. Aldesleukin:720,000 IU/kgIV every eight hours (+/-1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine:25 mg/m^2/day intravenous piggy-back(IVPB) daily for 5 days. Cyclophosphamide:60 mg/kg/day X 2 days IV. Young TIL:Day 0: Cells will be infused IV. Retreatment with standard preparative regimen+Young TIL Cells+pembrolizumab. Aldesleukin:720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine:25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days. Cyclophosphamide:60 mg/kg/day X 2 days IV. Young TIL: Day 0:Cells will be infused IV. Pembrolizumab:2 mg/kg IV on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Drug Administration |
|
| ||||||||||||||||||
| Retreatment After First Drug Administrat |
|
Not provided
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm 1N -Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin | Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen in participants without prior treatment pembrolizumab or nivolumab Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) Young TIL: Day 0: Cells will be infused intravenously (IV) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P | Number of participants with Grades 3-5 treatment-related adverse events were compared in Arm 1N and Arm 1P; and adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 3 is severe. Grade 4 is life-threatening, and Grade 5 is death related to adverse event. | One participant was not treated on Arm 1N. Pre-specified by the protocol, there are two combined reporting groups for this outcome. The first combined group (n=23) is all who received standard chemo (Arm 1N, Arm 1P, the retreatment of Arm 2/1P, and the initial treatment of Arm 1P/R). The second combined group (n=12) is all who received the reduced dose chemo (Arm 2, and the initial treatment of Arm 2/1P) This separates reporting of adverse events by the intensity of chemotherapy. | Posted | Count of Participants | Participants | 30 days after end of treatment |
|
Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm 1N -Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin | Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen in participants without prior treatment pembrolizumab or nivolumab Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) Young TIL: Day 0: Cells will be infused intravenously (IV) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ALT, SGPT (serum glutamic pyruvic transaminase) | Investigations | CTCAE (4.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ALT, SGPT (serum glutamic pyruvic transaminase) | Investigations | CTCAE (4.0) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Stephanie L. Goff | National Cancer Institute | 240-760-6214 | stephanie.goff@nih.gov |
Not provided
| 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 | Feb 15, 2019 | Sep 14, 2022 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Mar 11, 2019 | Sep 14, 2022 | ICF_001.pdf |
Not provided
| ID | Term |
|---|---|
| D008545 | Melanoma |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
Not provided
Not provided
| ID | Term |
|---|---|
| C082598 | aldesleukin |
| C024352 | fludarabine |
| C042382 | fludarabine phosphate |
| D003520 | Cyclophosphamide |
| C582435 | pembrolizumab |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
Not provided
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|
| Arm 2- Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin | Experimental | Decreased Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2 Lower Dose preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 30 mg/kg/day intravenous piggy-back (IVPB) daily for 3 days Cyclophosphamide: Days -5 to -3 (low-dose arm): Cyclophosphamide 30 mg/kg IV over 60 minutes for 2 days. Young TIL: Day 0: Cells will be infused intravenously (IV) |
|
| Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin | Experimental | Standard Chemo Prep Regimen(SCPR)+Retreat. Young TIL+High Dose(HD) Interleukin-2, SCPR. Young TIL+HD Interleukin-2, SC(Retreat). SCPR+Young TIL Cells retreatment with SCPR+Young TIL Cells+pembrolizumab. Aldesleukin:720,000 IU/kgIV every eight hours (+/-1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine:25 mg/m^2/day intravenous piggy-back(IVPB) daily for 5 days. Cyclophosphamide:60 mg/kg/day X 2 days IV. Young TIL:Day 0: Cells will be infused IV. Retreatment with standard preparative regimen+Young TIL Cells+pembrolizumab. Aldesleukin:720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine:25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days. Cyclophosphamide:60 mg/kg/day X 2 days IV. Young TIL: Day 0:Cells will be infused IV. Pembrolizumab:2 mg/kg IV on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days). |
|
|
| Fludarabine | Drug | 25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days |
|
|
| Fludarabine | Drug | 30 mg/kg/day intravenous piggy-back (IVPB) daily for 3 days. |
|
|
| Cyclophosphamide | Drug | 60 mg/kg/day X 2 days intravenous (IV) |
|
|
| Cyclophosphamide | Drug | Days -5 to -3 (low-dose arm):30 mg/kg IV over 60 minutes for 2 days |
|
|
| Cyclophosphamide | Drug | Days -5 to -3 (low-dose arm): 300 mg/m^2 IV over 60 minutes. |
|
|
| Young TIL | Biological | Day 0: Cells will be infused intravenously (IV) |
|
|
| Pembrolizumab | Drug | 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days). |
|
|
| Progression-free Survival (PFS) | PFS is defined as the time to disease progression following the start of treatment, and time to death following the start of treatment. Progression was assessed by the Response Evaluation Criteria In Solid Tumors (RECIST) v1.0 and is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | Date of cells until time of disease progression up to approximately 67.2 months. |
| Overall Survival | Overall survival is defined as the time from treatment start date until date of death, or date last known alive. | Date of cells until time to death, up until 90.1 months. |
| Overall Survival | Overall survival is defined as the time from treatment start date until date of death, or date last known alive. | An average of 25.6 months. |
| Overall Progression Free Survival (PFS) | PFS is defined as the time to disease progression following the start of treatment, and time to death following the start of treatment. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0 and is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | Time to progression and time to death, approximately up to 67.2 months. |
| Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively. |
| Background |
| O'Brien SM, Kantarjian HM, Cortes J, Beran M, Koller CA, Giles FJ, Lerner S, Keating M. Results of the fludarabine and cyclophosphamide combination regimen in chronic lymphocytic leukemia. J Clin Oncol. 2001 Mar 1;19(5):1414-20. doi: 10.1200/JCO.2001.19.5.1414. |
| COMPLETED |
|
| NOT COMPLETED |
|
| BG001 | Arm 1P - Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin | Standard Chemo Prep Regimen Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen in participants previously treated with pembrolizumab or nivolumab. Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) Young TIL: Day 0: Cells will be infused intravenously (IV) |
| BG002 | Arm 2/Foll By Arm 1P-Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin | Decreased Chemo Prep Regimen+Retreat. Young TIL+High Dose Interleukin-2, Decreased Chemo Preparative Regimen. Young TIL+High Dose Interleukin-2, Standard Chemo (Retreat). Lower dose preparative regimen + Young TIL Cells. Aldesleukin: 720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 30 mg/kg/day intravenous piggy-back (IVPB) daily for 3 days. Cyclophosphamide: Days -5 to -3 (low-dose arm): Cyclophosphamide 300 mg/m^2 IV over 60 minutes. Young TIL: Day 0: Cells will be infused IV. Retreatment: Standard Chemo Prep Regimen. Aldesleukin: 720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days. Cyclophosphamide: 60 mg/kg/day X 2 days IV. Young TIL: Day 0: Cells will be infused IV. |
| BG003 | Arm 2- Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin | Decreased Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2 Lower Dose preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 30 mg/kg/day intravenous piggy-back (IVPB) daily for 3 days Cyclophosphamide: Days -5 to -3 (low-dose arm): Cyclophosphamide 30 mg/kg IV over 60 minutes for 2 days. Young TIL: Day 0: Cells will be infused intravenously (IV) |
| BG004 | Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin | Standard Chemo Prep Regimen(SCPR)+Retreat. Young TIL+High Dose(HD) Interleukin-2, SCPR. Young TIL+HD Interleukin-2, SC(Retreat). SCPR+Young TIL Cells retreatment with SCPR+Young TIL Cells+pembrolizumab. Aldesleukin:720,000 IU/kgIV every eight hours (+/-1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine:25 mg/m^2/day intravenous piggy-back(IVPB) daily for 5 days. Cyclophosphamide:60 mg/kg/day X 2 days IV. Young TIL:Day 0: Cells will be infused IV. Retreatment with standard preparative regimen+Young TIL Cells+pembrolizumab. Aldesleukin:720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine:25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days. Cyclophosphamide:60 mg/kg/day X 2 days IV. Young TIL: Day 0:Cells will be infused IV. Pembrolizumab:2 mg/kg IV on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days). |
| BG005 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| 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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Grade 3 is severe. Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m^2 IV over 60 minutes. Young TIL: Day 0: Cells will be infused intravenously (IV) |
| OG001 | Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Grade 3 is severe. Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m^2 IV over 60 minutes. Young TIL: Day 0: Cells will be infused intravenously (IV) |
| OG002 | Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Grade 3 is severe. Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m^2 IV over 60 minutes. Young TIL: Day 0: Cells will be infused intravenously (IV) |
| OG003 | Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Grade 4 is life-threatening. Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m^2 IV over 60 minutes. Young TIL: Day 0: Cells will be infused intravenously (IV) |
| OG004 | Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Grade 4 is life-threatening. Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m^2 IV over 60 minutes. Young TIL: Day 0: Cells will be infused intravenously (IV) |
| OG005 | Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Grade 4 is life-threatening. Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m^2 IV over 60 minutes. Young TIL: Day 0: Cells will be infused intravenously (IV) |
| OG006 | Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P | Grade 5 is death related to adverse event. Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m^2 IV over 60 minutes. Young TIL: Day 0: Cells will be infused intravenously (IV) |
| OG007 | Grade 3 - Possibly Related Arm 2, Arm 2/1P | Grade 3 is severe. Cohort 1: 01 -> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat). Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m^2 IV over 60 minutes. Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days). |
| OG008 | Grade 3 - Probably Related Arm 2, Arm 2/1P | Grade 3 is severe. Cohort 1: 01 -> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat). Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m^2 IV over 60 minutes. Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days). |
| OG009 | Grade 3 - Definitely Related Arm 2, Arm 2/1P | Grade 3 is severe. Cohort 1: 01 -> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat). Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m^2 IV over 60 minutes. Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days). |
| OG010 | Grade 4 - Possibly Related Arm 2, Arm 2/1P | Grade 4 is life-threatening. Cohort 1: 01 -> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat). Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m^2 IV over 60 minutes. Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days). |
| OG011 | Grade 4 - Probably Related Arm 2, Arm 2/1P | Grade 4 is life-threatening. Cohort 1: 01 -> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat). Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m^2 IV over 60 minutes. Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days). |
| OG012 | Grade 4 - Definitely Related Arm 2, Arm 2/1P | Grade 4 is life-threatening. Cohort 1: 01 -> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat). Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m^2 IV over 60 minutes. Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days). |
| OG013 | Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P | Grade 5 is death related to adverse event. Cohort 1: 01 -> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat). Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m^2 IV over 60 minutes. Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days). |
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| Primary | Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression) | Clinical response to treatment was assessed by the Response Evaluation Criteria In Solid Tumors (RECIST v1.0). Complete Response (CR) is disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Progressive Disease (PD) is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD. | The first combined group (n=16) is Arm 1P, the second treatment of Arm 2/1P, the initial treatment of Arm 1P/R. The second group (n=7) is Arm 1N (1/8 participants was not treated). The third group (n=12) is Arm 2 and the initial treatment of Arm 2/1P. The final group (n=2) will report the second treatment of Arm 1P/R. This enables reporting of the 37 treatments among the 32 treated participants separated by exposure to pembrolizumab/nivolumab and chemo dose. | Posted | Count of Participants | Participants | 4 weeks after cell infusion, then every 3 months x 3 and then every 6 months for 5 years, then per Principal Investigator (PI) discretion up to 5 years or disease progression |
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| Primary | Overall Response Rate (ORR) | Overall response is the best response recorded from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.0). Progression is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | Retreat Arm 1N and Arm 2 Foll By Arm 1P not treated. | Posted | Number | 95% Confidence Interval | percentage of participants | Date of cells until time of disease progression, up to approximately 67.2 months. |
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| Secondary | Number of Treatment-related Adverse Events for Participants Who Received Pembrolizumab | Number of treatment-related adverse events for participants who received pembrolizumab. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. | Posted | Number | Adverse events | Date treatment consent signed until approximately 4 weeks following last dose of Pembrolizumab, up to 4 weeks |
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| Secondary | Progression-free Survival (PFS) | PFS is defined as the time to disease progression following the start of treatment, and time to death following the start of treatment. Progression was assessed by the Response Evaluation Criteria In Solid Tumors (RECIST) v1.0 and is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | The first combined group (n=16) is Arm 1P, the second treatment of Arm 2/1P, the initial treatment of Arm 1P/R. The second group (n=7) is Arm 1N (1/8 participants was not treated). The third group (n=12) is Arm 2 and the initial treatment of Arm 2/1P. The final group (n=2) will report the second treatment of Arm 1P/R. This enables reporting of the 37 treatments among the 32 treated participants separated by exposure to pembrolizumab/nivolumab and chemo dose. 0 participants analyzed= not treated. | Posted | Median | Full Range | Months | Date of cells until time of disease progression up to approximately 67.2 months. |
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| Secondary | Overall Survival | Overall survival is defined as the time from treatment start date until date of death, or date last known alive. | As pre-specified by the protocol, participants will be reported by the initial treatment arm: Arm 1N (n=7; 1/8 participants were not treated), Arm 1P (n=13), Arm 2 (n=12). | Posted | Median | Full Range | Months | Date of cells until time to death, up until 90.1 months. |
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| Secondary | Overall Survival | Overall survival is defined as the time from treatment start date until date of death, or date last known alive. | 1/8 participants were not treated in Arm 1N. | Posted | Median | Full Range | Months | An average of 25.6 months. |
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| Secondary | Overall Progression Free Survival (PFS) | PFS is defined as the time to disease progression following the start of treatment, and time to death following the start of treatment. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0 and is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | 1/8 participants were not treated in Arm 1N. | Posted | Median | Full Range | Months | Time to progression and time to death, approximately up to 67.2 months. |
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| Other Pre-specified | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) | Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. | 1/8 participants were not treated on Arm 1N. | Posted | Count of Participants | Participants | Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively. |
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| 2 |
| 7 |
| 3 |
| 7 |
| 7 |
| 7 |
| EG001 | Arm 1P - Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin | Standard Chemo Prep Regimen Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen in participants previously treated with pembrolizumab or nivolumab. Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) Young TIL: Day 0: Cells will be infused intravenously (IV) | 9 | 11 | 6 | 11 | 9 | 11 |
| EG002 | Arm 2/Foll By Arm 1P-Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin | Decreased Chemo Prep Regimen+Retreat. Young TIL+High Dose Interleukin-2, Decreased Chemo Preparative Regimen. Young TIL+High Dose Interleukin-2, Standard Chemo (Retreat). Lower dose preparative regimen + Young TIL Cells. Aldesleukin: 720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 30 mg/kg/day intravenous piggy-back (IVPB) daily for 3 days. Cyclophosphamide: Days -5 to -3 (low-dose arm): Cyclophosphamide 300 mg/m^2 IV over 60 minutes. Young TIL: Day 0: Cells will be infused IV. Retreatment: Standard Chemo Prep Regimen. Aldesleukin: 720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days. Cyclophosphamide: 60 mg/kg/day X 2 days IV. Young TIL: Day 0: Cells will be infused IV. | 2 | 3 | 1 | 3 | 3 | 3 |
| EG003 | Arm 2- Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin | Decreased Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2 Lower Dose preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 30 mg/kg/day intravenous piggy-back (IVPB) daily for 3 days Cyclophosphamide: Days -5 to -3 (low-dose arm): Cyclophosphamide 30 mg/kg IV over 60 minutes for 2 days. Young TIL: Day 0: Cells will be infused intravenously (IV) | 8 | 9 | 2 | 9 | 9 | 9 |
| EG004 | Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin | Standard Chemo Prep Regimen(SCPR)+Retreat. Young TIL+High Dose(HD) Interleukin-2, SCPR. Young TIL+HD Interleukin-2, SC(Retreat). SCPR+Young TIL Cells retreatment with SCPR+Young TIL Cells+pembrolizumab. Aldesleukin:720,000 IU/kgIV every eight hours (+/-1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine:25 mg/m^2/day intravenous piggy-back(IVPB) daily for 5 days. Cyclophosphamide:60 mg/kg/day X 2 days IV. Young TIL:Day 0: Cells will be infused IV. Retreatment with standard preparative regimen+Young TIL Cells+pembrolizumab. Aldesleukin:720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine:25 mg/m^2/day intravenous piggy-back (IVPB) daily for 5 days. Cyclophosphamide:60 mg/kg/day X 2 days IV. Young TIL: Day 0:Cells will be infused IV. Pembrolizumab:2 mg/kg IV on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days). | 1 | 2 | 1 | 2 | 2 | 2 |
| AST, SGOT(serum glutamic oxaloacetic transaminase) | Investigations | CTCAE (4.0) | Systematic Assessment |
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| Allergic reaction/hypersensitivity (including drug fever) | Immune system disorders | CTCAE (4.0) | Systematic Assessment |
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| Confusion | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
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| Febrile neutropenia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment | (fever of unknown origin without clinically or microbiologically documented infection)(ANC <1.0 x 10e9/L, fever >=38.5 degrees C) |
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| Hemoglobin | Investigations | CTCAE (4.0) | Systematic Assessment |
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| Hypotension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
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| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment | (documented clinically or microbiologically) with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L)::Blood |
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| Left ventricular systolic dysfunction | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
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| Lymphopenia | Investigations | CTCAE (4.0) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Neutrophil count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
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| Neutrophils/granulocytes (ANC/AGC) | Investigations | CTCAE (4.0) | Systematic Assessment |
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| Platelets | Investigations | CTCAE (4.0) | Systematic Assessment |
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| Renal failure | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Weight loss | Investigations | CTCAE (4.0) | Systematic Assessment |
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| AST, SGOT(serum glutamic oxaloacetic transaminase) | Investigations | CTCAE (4.0) | Systematic Assessment |
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| Allergic reaction/hypersensitivity (including drug fever) | Immune system disorders | CTCAE (4.0) | Systematic Assessment |
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| Anorexia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
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| Bilirubin (hyperbilirubinemia) | Investigations | CTCAE (4.0) | Systematic Assessment |
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| Confusion | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
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| Creatinine | Investigations | CTCAE (4.0) | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Dyspnea (shortness of breath) | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Fatigue (asthenia, lethargy, malaise) | General disorders | CTCAE (4.0) | Systematic Assessment |
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| Febrile neutropenia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
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| Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L) | General disorders | CTCAE (4.0) | Systematic Assessment |
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| Hemoglobin | Investigations | CTCAE (4.0) | Systematic Assessment |
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| Hemorrhage, GU::Vagina | Reproductive system and breast disorders | CTCAE (4.0) | Systematic Assessment |
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| Hypopigmentation | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
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| Hypotension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
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| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment | (documented clinically or microbiologically) with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L)::Blood |
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| Leukocytes (total WBC) | Investigations | CTCAE (4.0) | Systematic Assessment |
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| Lymphopenia | Investigations | CTCAE (4.0) | Systematic Assessment |
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| Mood alteration::Agitation | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Neutrophils/granulocytes (ANC/AGC) | Investigations | CTCAE (4.0) | Systematic Assessment |
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| PTT (Partial Thromboplastin Time) | Investigations | CTCAE (4.0) | Systematic Assessment |
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| Pain::Head/headache | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
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| Pain::Tumor pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | CTCAE (4.0) | Systematic Assessment |
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| Phosphate, serum-low (hypophosphatemia) | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
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| Platelets | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Pruritus/itching | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Psychosis (hallucinations/delusions) | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
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| Rash/desquamation | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
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| Renal failure | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
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| Renal/Genitourinary - Other (oliguria) | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
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| Rigors/chills | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Supraventricular and nodal arrhythmia::Sinus tachycardia | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| Thrombosis/thrombus/embolism | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| Thyroid function, low (hypothyroidism) | Endocrine disorders | CTCAE (4.0) | Systematic Assessment |
|
| Uric acid, serum-high (hyperuricemia) | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Uveitis | Eye disorders | CTCAE (4.0) | Systematic Assessment |
|
| Vision-blurred vision | Eye disorders | CTCAE (4.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Leukocytes (total white blood cell (WBC) | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Vision-blurred vision | Eye disorders | CTCAE (4.0) | Systematic Assessment |
|
Not provided
Not provided
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| First Treatment - Partial Response |
|
| First Treatment - Progressive Disease |
|
| First Treatment - Stable Disease |
|
| Second Treatment - Complete Response |
|
| Second Treatment - Partial Response |
|
| Second Treatment - Progressive Disease |
|
| Second Treatment - Stable Disease |
|
|
| Retreat |
|
|
|
| Retreat |
|
|