CompletedNCT01993719Updated Jan 18, 2023Results posted

Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Melanoma

A Phase 2 interventional study of Aldesleukin and Fludarabine in Metastatic Melanoma, sponsored by National Cancer Institute (NCI). Completed at 1 site in United States. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2023-01-18.

Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 33
Allocation: Non-randomized
Ages: 18 Years to 70 Years
Sex: All

Study summary

Background:

The National Cancer Institute (NCI) Surgery Branch has developed an experimental therapy that involves taking white blood cells from patients' tumors, growing them in the laboratory in large numbers, and then giving the cells back to the patient. These cells are called Tumor Infiltrating Lymphocytes, or TIL and we have given this type of treatment to over 400 patients with melanoma.
In this trial, we are determining if there is a difference in the response between patients who have received prior anti-programmed cell death-1 (PD-1) treatment to those who have not received this prior ant-PD1 treatment.

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:

Work up stage: Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.
Surgery: Surgery or biopsy will be performed to obtain tumor from which to grow white blood cells. White blood cells will be grown from the tumor in the laboratory.
Leukapheresis: Participants will have leukapheresis to collect additional white blood cells. (Leukapheresis is a common procedure which removes only the white blood cells from the patient.)
Treatment: Participants will receive standard dose chemotherapy to prepare their immune system to accept the white blood cells. Participants will receive an infusion of their own white blood cells grown from tumor. They will also receive aldesleukin for up to five days to boost the immune system s response to the white blood cells. They will stay in the hospital for about 4 weeks for the treatment.
Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits take up to 2 days.

Read the detailed description

Background:

Adoptive cell therapy (ACT) using autologous tumor infiltrating lymphocytes can mediate the regression of bulky metastatic melanoma when administered along with high-dose aldesleukin (IL-2) following a non-myeloablative lymphodepleting chemotherapy preparative regimen consisting of cyclophosphamide and fludarabine.
In a series of consecutive trials using this chemotherapy preparative regimen alone or with 2 Gray (Gy) or 12 Gy total body irradiation (TBI) objective response rates using Response Evaluation Criteria In Solid Tumors (RECIST) criteria were 49%, 52%, and 72%, respectively. Of the 20 complete regressions seen in this trial, 19 are on-going at 70 to 114 months.
The chemotherapy alone preparative regimen required in-patient treatment and was associated with significant neutropenia and thrombocytopenia requiring multiple transfusions and treatment for febrile neutropenia.

Objectives:

With amendment D, 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; both groups will receive non-myeloablative lymphoid depleting preparative regimen followed by autologous young tumor infiltrating lymphocytes (TIL) and administration of high dose aldesleukin.
To determine the toxicity of the treatment.

Eligibility:

Age greater than or equal to 18 and less than or equal to 70 years
Evaluable metastatic melanoma
Metastatic melanoma lesion suitable for surgical resection for the preparation of TIL
No contraindications to high-dose aldesleukin administration
No concurrent major medical illnesses or any form of immunodeficiency

Design:

Patients with metastatic melanoma will have lesions resected and after TIL growth is established, patients will receive ACT with TIL plus aldesleukin following high dose chemotherapy preparative regimen.
Up to 64 patients may be enrolled over 4-5 years.

Conditions studied

Metastatic Melanoma

Browse trials for

Melanoma 3,006

Keywords

Melanoma
Adoptive Cell Therapy

In context

Melanoma

3,006 studies on the registry are indexed under Melanoma; 520 are open to participants now.

This study's enrollment of 33 is below the median of 38 across 2,351 interventional studies indexed under Melanoma.

Browse Melanoma studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 70 Years
Sexes eligible: All
Accepts healthy volunteers: No

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:
- Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus are less responsive to the experimental treatment and more susceptible to its toxicities.)
- Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by reverse transcription polymerase chain reaction (RT-PCR) and be hepatitis C virus (HCV) ribonucleic acid (RNA) negative.
Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus.
Hematology:
- Absolute neutrophil count greater than 1000/mm(3) without the support of filgrastim
- White blood cell (WBC) greater than or equal to 3000/mm(3)
- Platelet count greater than or equal to 100,000/mm(3)
- Hemoglobin > 8.0 g/dl
Chemistry:
- Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than or equal to 2.5 times the upper limit of normal
- Serum Creatinine less than or equal to 1.6 mg/dl
- Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.
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

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:
- Age greater than or equal to 65 years old
- Clinically significant atrial and or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or history of ischemic heart disease or chest pain.
Patients who are receiving other investigational agents
Documented forced expiratory volume (FEV1) less than or equal to 60% predicted tested in patients with:
- A prolonged history of cigarette smoking (20 pack (pk)/year of smoking within the past 2 years).
- Symptoms of respiratory dysfunction

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 33 participants (actual)

Study arms

Experimental
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)
Drug: Aldesleukin · Drug: Fludarabine · Drug: Cyclophosphamide · Biological: Young TIL
Experimental
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)
Drug: Aldesleukin · Drug: Fludarabine · Drug: Cyclophosphamide · Biological: Young TIL
Experimental
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.
Drug: Aldesleukin · Drug: Fludarabine · Drug: Cyclophosphamide · Biological: Young TIL
Experimental
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)
Drug: Aldesleukin · Drug: Fludarabine · Drug: Cyclophosphamide · Biological: Young TIL
Experimental
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).
Drug: Aldesleukin · Drug: Fludarabine · Drug: Cyclophosphamide · Biological: Young TIL · Drug: Pembrolizumab

Interventions

DrugAldesleukin
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).
Also known as: Proleukin
DrugFludarabine
25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days
Also known as: Fludara
DrugFludarabine
30 mg/kg/day intravenous piggy-back (IVPB) daily for 3 days.
Also known as: Fludara
DrugCyclophosphamide
60 mg/kg/day X 2 days intravenous (IV)
Also known as: Cytoxan
DrugCyclophosphamide
Days -5 to -3 (low-dose arm):30 mg/kg IV over 60 minutes for 2 days
Also known as: Cytoxan
DrugCyclophosphamide
Days -5 to -3 (low-dose arm): 300 mg/m\^2 IV over 60 minutes.
Also known as: Cytoxan
BiologicalYoung TIL
Day 0: Cells will be infused intravenously (IV)
Also known as: Young Tumor Infiltrating Lymphocytes
DrugPembrolizumab
2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
Also known as: Keytruda

What researchers measure

Primary outcomes

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.
Time frame: 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.
Time frame: 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.
Time frame: Date of cells until time of disease progression, up to approximately 67.2 months.

Secondary outcomes

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.
Time frame: Date treatment consent signed until approximately 4 weeks following last dose of Pembrolizumab, up to 4 weeks
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 frame: 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.
Time frame: 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.
Time frame: 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 frame: Time to progression and time to death, approximately up to 67.2 months.

Other outcomes

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.
Time frame: 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.

Results

Posted Jan 18, 2023

Participant flow

First Drug Administration

Participant flow — First Drug Administration
Milestone	Arm 1N -Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1P - Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 2/Foll By Arm 1P-Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 2- Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
Started	8	11	3	9	2
Completed	7	11	3	9	2
Not completed	1	0	0	0	0
Withdrew: Not treated	1	0	0	0	0

Retreatment After First Drug Administrat

Participant flow — Retreatment After First Drug Administrat
Milestone	Arm 2/Foll By Arm 1P-Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
Started	3	2
Completed	3	2
Not completed	0	0

Outcome measures

PrimaryNumber 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.

Time frame:: 30 days after end of treatment
Reported as:: Count of participants · Participants

Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
Participants	Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P	Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P	Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P	Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P	Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P	Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P	Grade 3 - Possibly Related Arm 2, Arm 2/1P	Grade 3 - Probably Related Arm 2, Arm 2/1P	Grade 3 - Definitely Related Arm 2, Arm 2/1P	Grade 4 - Possibly Related Arm 2, Arm 2/1P	Grade 4 - Probably Related Arm 2, Arm 2/1P	Grade 4 - Definitely Related Arm 2, Arm 2/1P
ALT, SGPT (serum glutamic pyruvic transaminase)	0	2	0	0	0	0	1	0	0	0	0	0
AST, SGOT(serum glutamic oxaloacetic transaminase)	0	1	0	0	0	0	1	1	0	0	0	0
Allergic reaction/hypersensitivity (including drug fever)	0	1	0	0	0	0	0	0	0	0	0	0
Bilirubin (hyperbilirubinemia)	0	1	1	0	0	0	0	0	0	0	0	0
Confusion	0	0	0	0	1	0	0	0	0	0	0	0
Creatinine	0	1	3	0	0	0	0	0	0	0	0	0
Diarrhea	0	0	1	0	0	0	0	0	0	0	0	0
Febrile neutropenia	0	3	4	0	2	0	0	0	0	0	0	0
Hemoglobin	4	2	6	1	0	0	2	1	3	0	0	0
Hemorrhage, GU::Vagina	0	1	0	0	0	0	0	0	0	0	0	0
Hypotension	0	2	0	0	0	0	0	3	0	1	0	0
Hypoxia	0	2	0	0	0	0	0	0	0	0	0	0
Infection (documented clinically or microbiologically) w/Grade 3/4 neutrophils(ANC <1.0x10e9/L)Blood	1	2	1	0	1	0	0	0	0	0	0	0
Left ventricular systolic dysfunction	0	1	0	0	0	0	0	0	0	0	0	0
Leukocytes (total WBC)	0	0	1	0	0	1	0	0	0	0	0	0
Lymphopenia	0	0	1	0	2	14	0	0	0	0	2	9
Nausea	0	0	0	1	0	0	0	0	0	0	0	0
Neutrophils/granulocytes (ANC/AGC)	0	0	2	0	1	14	0	0	2	0	0	4
PTT (Partial Thromboplastin Time)	0	2	2	0	0	0	0	2	0	0	0	0
Phosphate, serum-low (hypophosphatemia)	1	0	0	0	0	0	0	0	0	0	0	0
Platelets	0	1	4	0	0	11	0	0	0	0	0	2
Renal failure	0	2	0	0	0	0	0	2	0	0	0	0
Renal/Genitourinary - Other (Specify, oliguria)	0	1	0	0	0	0	0	1	0	0	0	0
Uric acid, serum-high (hyperuricemia)	0	0	0	0	1	0	0	0	0	0	1	0
Vomiting	0	0	0	1	0	0	0	0	0	0	0	0
Weight loss	1	0	0	0	0	0	0	0	0	0	0	0

PrimaryNumber 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.

Time frame:: 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
Reported as:: Count of participants · Participants

Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression)
Participants	Arm 1P - Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1N -Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 2/Foll By Arm 1P-Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
First Treatment - Complete Response	0	2	0	NA
First Treatment - Partial Response	2	2	2	NA
First Treatment - Progressive Disease	8	2	0	NA
First Treatment - Stable Disease	3	1	1	NA
Second Treatment - Complete Response	0	NA	NA	0
Second Treatment - Partial Response	1	NA	NA	1
Second Treatment - Progressive Disease	1	NA	NA	1
Second Treatment - Stable Disease	1	NA	NA	0

PrimaryOverall 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.

Time frame:: Date of cells until time of disease progression, up to approximately 67.2 months.
Reported as:: Number · percentage of participants

Overall Response Rate (ORR)
percentage of participants	Arm 1P - Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1N -Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 2/Foll By Arm 1P-Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
Initial Treatment	23.10 (8.2 to 50.3)	57.10 (25 to 84.1)	16.70 (3 to 44.8)	—
Retreat	33.30 (1.7 to 88.2)	—	—	50 (2.6 to 97.4)

SecondaryNumber 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.

Time frame:: Date treatment consent signed until approximately 4 weeks following last dose of Pembrolizumab, up to 4 weeks
Reported as:: Number · Adverse events

Number of Treatment-related Adverse Events for Participants Who Received Pembrolizumab
Adverse events	Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
Number of Treatment-related Adverse Events for Participants Who Received Pembrolizumab	16

SecondaryProgression-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 frame:: Date of cells until time of disease progression up to approximately 67.2 months.
Reported as:: Median · Months

Progression-free Survival (PFS)
Months	Arm 1P - Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1N -Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 2/Foll By Arm 1P-Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
Initial Treatment	3.1 (1.3 to 14.6)	7.9 (2 to NA)	2.1 (0.9 to 12.8)	—
Retreat	1.6 (0.1 to 5.3)	—	—	32.5 (2.3 to NA)

SecondaryOverall Survival

Overall survival is defined as the time from treatment start date until date of death, or date last known alive.

Time frame:: Date of cells until time to death, up until 90.1 months.
Reported as:: Median · Months

Overall Survival
Months	Arm 1P - Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1N -Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 2- Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
Overall Survival	14.3 (2.3 to NA)	NA (18.7 to NA)	15.1 (5.4 to NA)

SecondaryOverall Survival

Overall survival is defined as the time from treatment start date until date of death, or date last known alive.

Time frame:: An average of 25.6 months.
Reported as:: Median · Months

Overall Survival
Months	All Participants in Arms 1N, 1P, Arm 2/Foll By Arm 1P, Arm 2, and Arm 1P/Foll By Arm 1P/R
Overall Survival	17.5 (2.3 to NA)

SecondaryOverall 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 frame:: Time to progression and time to death, approximately up to 67.2 months.
Reported as:: Median · Months

Overall Progression Free Survival (PFS)
Months	All Participants in Arms 1N, 1P, Arm 2/Foll By Arm 1P, Arm 2, and Arm 1P/Foll By Arm 1P/R
Overall Progression Free Survival (PFS)	3 (0.9 to NA)

Other pre-specifiedNumber 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.

Time frame:: 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.
Reported as:: Count of participants · Participants

Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
Participants	Arm 1N -Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1P - Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 2/Foll By Arm 1P-Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 2- Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)	7	9	3	9	2

Adverse events

Collected over 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.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Arm 1N -Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	2/7 (28.6%)	3/7 (42.9%)	7/7 (100%)
Arm 1P - Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	9/11 (81.8%)	6/11 (54.5%)	9/11 (81.8%)
Arm 2/Foll By Arm 1P-Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	2/3 (66.7%)	1/3 (33.3%)	3/3 (100%)
Arm 2- Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	8/9 (88.9%)	2/9 (22.2%)	9/9 (100%)
Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	1/2 (50%)	1/2 (50%)	2/2 (100%)

Most frequent serious events

Showing 10 of 18

Most frequent serious events
Event	Arm 1N -Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1P - Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 2/Foll By Arm 1P-Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 2- Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
HemoglobinInvestigations	0/7	2/11	0/3	0/9	1/2
NauseaGastrointestinal disorders	0/7	0/11	0/3	0/9	1/2
VomitingGastrointestinal disorders	0/7	0/11	0/3	0/9	1/2
Weight lossInvestigations	0/7	0/11	0/3	0/9	1/2
InfectionInfections and infestations	3/7	1/11	0/3	0/9	0/2
LymphopeniaInvestigations	0/7	0/11	1/3	0/9	0/2
Renal failureRenal and urinary disorders	0/7	0/11	1/3	1/9	0/2
Febrile neutropeniaBlood and lymphatic system disorders	0/7	2/11	0/3	0/9	0/2
ConfusionPsychiatric disorders	1/7	0/11	0/3	0/9	0/2
Left ventricular systolic dysfunctionCardiac disorders	1/7	0/11	0/3	0/9	0/2

Most frequent other events

Showing 10 of 43

Most frequent other events
Event	Arm 1N -Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1P - Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 2/Foll By Arm 1P-Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 2- Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
HemoglobinInvestigations	2/7	4/11	3/3	2/9	1/2
LymphopeniaInvestigations	4/7	7/11	2/3	8/9	2/2
Neutrophils/granulocytes (ANC/AGC)Investigations	4/7	7/11	2/3	4/9	2/2
PlateletsInvestigations	4/7	6/11	2/3	0/9	2/2
Fatigue (asthenia, lethargy, malaise)General disorders	0/7	2/11	2/3	4/9	1/2
HypotensionVascular disorders	1/7	2/11	2/3	4/9	0/2
PTT (Partial Thromboplastin Time)Investigations	0/7	2/11	2/3	1/9	0/2
ConfusionPsychiatric disorders	1/7	1/11	0/3	0/9	1/2
Dyspnea (shortness of breath)Respiratory, thoracic and mediastinal disorders	1/7	0/11	1/3	1/9	1/2
Hemorrhage, GU::VaginaReproductive system and breast disorders	0/7	0/11	0/3	0/9	1/2

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Arm 1N -Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1P - Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 2/Foll By Arm 1P-Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 2- Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Total
<=18 years	0	0	0	0	0	0
Between 18 and 65 years	8	10	3	9	2	32
>=65 years	0	1	0	0	0	1

Age, Continuous
Age, Continuous(years)	Arm 1N -Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1P - Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 2/Foll By Arm 1P-Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 2- Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Total
Mean	46.28 ± 1.43	56.28 ± 13.39	31.07 ± 13.25	44.72 ± 3.66	53 ± 3.39	46.45 ± 13.97

Sex: Female, Male
Sex: Female, Male(Participants)	Arm 1N -Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1P - Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 2/Foll By Arm 1P-Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 2- Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Total
Female	2	2	2	4	1	11
Male	6	9	1	5	1	22

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Arm 1N -Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1P - Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 2/Foll By Arm 1P-Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 2- Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Total
Hispanic or Latino	0	0	0	0	0	0
Not Hispanic or Latino	8	11	3	9	2	33
Unknown or Not Reported	0	0	0	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Arm 1N -Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1P - Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 2/Foll By Arm 1P-Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 2- Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Total
American Indian or Alaska Native	0	0	0	0	0	0
Asian	0	0	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0
Black or African American	0	0	0	0	0	0
White	8	11	3	9	2	33
More than one race	0	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0	0

Region of Enrollment
Region of Enrollment(participants)	Arm 1N -Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1P - Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 2/Foll By Arm 1P-Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 2- Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin	Total
United States	8	11	3	9	2	33

Study locations

1 site

National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland 20892, United States

References and documents

Publications

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. PubMed 18809613 ↗
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. PubMed 11230486 ↗

Study documents

Protocol and statistical analysis plan · Feb 15, 2019
Informed consent form · Mar 11, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.

Supporting information: Study protocol, Sap, Icf

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jan 18, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01993719
Lead sponsor: National Cancer Institute (NCI)
Responsible party: Stephanie Goff (Principal Investigator, National Cancer Institute (NCI)) — Principal investigator
First posted: Nov 25, 2013
Start date: Dec 12, 2013
Primary completion: Oct 14, 2021
Completion: Jul 6, 2022
Results posted: Jan 18, 2023
Last update: Jan 18, 2023

Study contacts

Stephanie L Goff, M.D.

principal investigator · National Cancer Institute (NCI)

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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