Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Chemotherapy Followed by ESO-1 Lymphocytes and Aldesleukin to Treat Metastatic Cancer

This study has been terminated.
(A more highly selected protocol with ESO TCR opened for pts with melanoma)
Sponsor:
Information provided by (Responsible Party):
Steven Rosenberg, M.D., National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00670748
First received: May 1, 2008
Last updated: October 26, 2016
Last verified: October 2016
Results First Received: May 19, 2016  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Metastatic Melanoma
Metastatic Renal Cell Cancer
Metastatic Cancer
Interventions: Biological: Anti-NY ESO-1 T-cell receptor PBL
Drug: aldesleukin
Drug: Cyclophosphamide
Drug: fludarabine phosphate
Biological: ALVAC NY ESO-1 vaccine

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
#1 Anti-NY-ESO-1 TCR PBL+HD IL-2 Mel/RCC

Biological/Vaccine: Anti-NY ESO-1 T-cell receptor PBL Patients will receive non-myeloablative lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine followed by the administration of anti-NY ESO-1 T-cell receptor (TCR) peripheral blood lymphocytes (PBL) and high dose aldesleukin. On day 0,cells (1x10e8 to 1x10e11)will be infused intravenously on the Patient Care Unit over 20-30 minutes.

Drug: aldesleukin Aldesleukin 720,000 IU/kg intravenous (IV) (based on total body weight)over 15 minutes every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 5 days(maximum of 15 doses) Drug: Cyclophosphamide Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml dextrose 5% in water (D5W) with Mesna 15 mg/kg/day X 2 days over 1 hr.

Drug: fludarabine phosphate Fludarabine 25 mg/m2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days.

#2 Anti-NY-ESO-1 TCR PBL+HD IL-2 OtherCa

Biological/Vaccine: Anti-NY ESO-1 T-cell receptor PBL Patients will receive non-myeloablative lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine followed by the administration of anti-NY ESO-1 T-cell receptor (TCR) peripheral blood lymphocytes (PBL) and high dose aldesleukin. On day 0,cells (1x10e8 to 1x10e11)will be infused intravenously on the Patient Care Unit over 20-30 minutes.

Drug: aldesleukin Aldesleukin 720,000 IU/kg intravenous (IV) (based on total body weight)over 15 minutes every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 5 days(maximum of 15 doses) Drug: Cyclophosphamide Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml dextrose 5% in water (D5W) with Mesna 15 mg/kg/day X 2 days over 1 hr.

Drug: fludarabine phosphate Fludarabine 25 mg/m2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days.

#3ESO1 TCR PBL+ALVAC ESO1+HD IL2 Mel/RCC

Pts will receive non-myeloablative lymphodepleting prep regimen:cyclophosphamide & fludarabine followed by the anti-NY ESO-1 T-cell receptor (TCR) peripheral blood lymphocytes (PBL) & high dose aldesleukin. On day 0,cells (1x10e8 to 1x10e11)will be infused intravenously on the Pt Care Unit over 20-30 min. Aldesleukin 720,000 IU/kg intravenous (IV) (based on total body wt)over 15 min. every 8 hrs (+/-1 hr) beginning within 24 hrs of cell infusion and continuing for up to 5 days(max. of 15 doses).Cyclophosphamide 60 mg/kg/dayX2 days IV in 250 ml dextrose 5% in water (D5W) with Mesna 15 mg/kg/dayX2 days over 1 hr.

Fludarabine 25 mg/m2/day intravenous piggyback (IVPB) daily over 30 min. for 5 days.

ALVAC NY ESO-1 vaccine:Approx. 2hrs prior to cell infusion, pts will receive 0.5 mL containing a target dose of 10e7 cell culture infectious dose 50 (CCID50)(with a range of approx. 10e6.4 to 10e7.9 / mL) of the ESO-1 ALVAC virus S.C. in each extremity (total of 4 x 10e7 CCID50/2 mL.

#4ESO1 TCR PBL+ALVAC ESO1+HD IL2 OtherCa Anti-NY ESO-1 T-cell receptor PBL; Pts will receive non-myeloablative lymphodepleting prep regimen cyclophosphamide and fludarabine followed by anti-NY ESO-1 T-cell receptor (TCR) peripheral blood lymphocytes (PBL) and high dose aldesleukin. On day 0,cells (1x10e8 to 1x10e11)will be infused intravenously on the Pt Care Unit over 20-30 min. Aldesleukin 720,000 IU/kg IV (based on total body wt)over 15 min. every 8 hours (+/-1 hr) beginning within 24 hrs of cell infusion and continuing for up to 5 days(max. of 15 doses). Cyclophosphamide 60 mg/kg/dayX2 days IV in 250 ml dextrose 5% in water (D5W) with Mesna 15 mg/kg/dayX2 days over 1 hr. Fludarabine 25 mg/m2/day IVPB daily over 30 min. for 5 days. ALVAC NY ESO-1 vaccine:Approx. 2 hrs prior to cell infusion, patients will receive 0.5 mL containing a target dose of 10e7 cell culture infectious dose 50 (CCID50) (with a range of approx.10e6.4 to 10e7.9 / mL) of the ESO-1 ALVAC virus S.C. in each extremity (total of 4 x 10e7 CCID50/2 mL.

Participant Flow:   Overall Study
    #1 Anti-NY-ESO-1 TCR PBL+HD IL-2 Mel/RCC   #2 Anti-NY-ESO-1 TCR PBL+HD IL-2 OtherCa   #3ESO1 TCR PBL+ALVAC ESO1+HD IL2 Mel/RCC   #4ESO1 TCR PBL+ALVAC ESO1+HD IL2 OtherCa
STARTED   17   16   7   5 
COMPLETED   14   14   5   4 
NOT COMPLETED   3   2   2   1 
Death during treatment                1                1                1                0 
Not off study                2                1                1                1 



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
#1 Anti-NY-ESO-1 TCR PBL+HD IL-2 Mel/RCC

Biological/Vaccine: Anti-NY ESO-1 T-cell receptor PBL Patients will receive non-myeloablative lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine followed by the administration of anti-NY ESO-1 T-cell receptor (TCR) peripheral blood lymphocytes (PBL) and high dose aldesleukin. On day 0,cells (1x10e8 to 1x10e11)will be infused intravenously on the Patient Care Unit over 20-30 minutes.

Drug: aldesleukin Aldesleukin 720,000 IU/kg intravenous (IV) (based on total body weight)over 15 minutes every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 5 days(maximum of 15 doses) Drug: Cyclophosphamide Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml dextrose 5% in water (D5W) with Mesna 15 mg/kg/day X 2 days over 1 hr.

Drug: fludarabine phosphate Fludarabine 25 mg/m2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days.

#2 Anti-NY-ESO-1 TCR PBL+HD IL-2 OtherCa

Biological/Vaccine: Anti-NY ESO-1 T-cell receptor PBL Patients will receive non-myeloablative lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine followed by the administration of anti-NY ESO-1 T-cell receptor (TCR) peripheral blood lymphocytes (PBL) and high dose aldesleukin. On day 0,cells (1x10e8 to 1x10e11)will be infused intravenously on the Patient Care Unit over 20-30 minutes.

Drug: aldesleukin Aldesleukin 720,000 IU/kg intravenous (IV) (based on total body weight)over 15 minutes every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 5 days(maximum of 15 doses) Drug: Cyclophosphamide Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml dextrose 5% in water (D5W) with Mesna 15 mg/kg/day X 2 days over 1 hr.

Drug: fludarabine phosphate Fludarabine 25 mg/m2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days.

#3ESO1 TCR PBL+ALVAC ESO1+HD IL2 Mel/RCC

Pts will receive non-myeloablative lymphodepleting prep regimen:cyclophosphamide & fludarabine followed by the anti-NY ESO-1 T-cell receptor (TCR) peripheral blood lymphocytes (PBL) & high dose aldesleukin. On day 0,cells (1x10e8 to 1x10e11)will be infused intravenously on the Pt Care Unit over 20-30 min. Aldesleukin 720,000 IU/kg intravenous (IV) (based on total body wt)over 15 min. every 8 hrs (+/-1 hr) beginning within 24 hrs of cell infusion and continuing for up to 5 days(max. of 15 doses).Cyclophosphamide 60 mg/kg/dayX2 days IV in 250 ml dextrose 5% in water (D5W) with Mesna 15 mg/kg/dayX2 days over 1 hr.

Fludarabine 25 mg/m2/day intravenous piggyback (IVPB) daily over 30 min. for 5 days.

ALVAC NY ESO-1 vaccine:Approx. 2hrs prior to cell infusion, pts will receive 0.5 mL containing a target dose of 10e7 cell culture infectious dose 50 (CCID50)(with a range of approx. 10e6.4 to 10e7.9 / mL) of the ESO-1 ALVAC virus S.C. in each extremity (total of 4 x 10e7 CCID50/2 mL.

#4ESO1 TCR PBL+ALVAC ESO1+HD IL2 OtherCa Anti-NY ESO-1 T-cell receptor PBL; Pts will receive non-myeloablative lymphodepleting prep regimen cyclophosphamide and fludarabine followed by anti-NY ESO-1 T-cell receptor (TCR) peripheral blood lymphocytes (PBL) and high dose aldesleukin. On day 0,cells (1x10e8 to 1x10e11)will be infused intravenously on the Pt Care Unit over 20-30 min. Aldesleukin 720,000 IU/kg IV (based on total body wt)over 15 min. every 8 hours (+/-1 hr) beginning within 24 hrs of cell infusion and continuing for up to 5 days(max. of 15 doses). Cyclophosphamide 60 mg/kg/dayX2 days IV in 250 ml dextrose 5% in water (D5W) with Mesna 15 mg/kg/dayX2 days over 1 hr. Fludarabine 25 mg/m2/day IVPB daily over 30 min. for 5 days. ALVAC NY ESO-1 vaccine:Approx. 2 hrs prior to cell infusion, patients will receive 0.5 mL containing a target dose of 10e7 cell culture infectious dose 50 (CCID50) (with a range of approx.10e6.4 to 10e7.9 / mL) of the ESO-1 ALVAC virus S.C. in each extremity (total of 4 x 10e7 CCID50/2 mL.
Total Total of all reporting groups

Baseline Measures
   #1 Anti-NY-ESO-1 TCR PBL+HD IL-2 Mel/RCC   #2 Anti-NY-ESO-1 TCR PBL+HD IL-2 OtherCa   #3ESO1 TCR PBL+ALVAC ESO1+HD IL2 Mel/RCC   #4ESO1 TCR PBL+ALVAC ESO1+HD IL2 OtherCa   Total 
Overall Participants Analyzed 
[Units: Participants]
 17   16   7   5   45 
Age 
[Units: Participants]
         
<=18 years   0   0   0   0   0 
Between 18 and 65 years   16   14   7   5   42 
>=65 years   1   2   0   0   3 
Age 
[Units: Years]
Mean (Standard Deviation)
 49.2  (11.6)   38.9  (14.1)   44.4  (10.4)   38.8  (16.0)   43.6  (13.3) 
Gender 
[Units: Participants]
         
Female   5   7   2   2   16 
Male   12   9   5   3   29 
Ethnicity (NIH/OMB) 
[Units: Participants]
         
Hispanic or Latino   2   1   1   0   4 
Not Hispanic or Latino   15   15   6   5   41 
Unknown or Not Reported   0   0   0   0   0 
Race (NIH/OMB) 
[Units: Participants]
         
American Indian or Alaska Native   0   0   0   0   0 
Asian   0   1   0   0   1 
Native Hawaiian or Other Pacific Islander   0   0   0   0   0 
Black or African American   0   0   0   0   0 
White   15   14   6   5   40 
More than one race   0   0   0   0   0 
Unknown or Not Reported   2   1   1   0   4 
Region of Enrollment 
[Units: Participants]
         
United States   17   16   7   5   45 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Clinical Response Per the Response Evaluation Criteria in Solid Tumors (RECIST)   [ Time Frame: Approximately 3 years ]

2.  Secondary:   Number of Participants With In Vivo Survival of T-Cell Receptor (TCR)-Engineered Cells   [ Time Frame: 1 month post treatment ]

3.  Secondary:   Number of Participants With Adverse Events   [ Time Frame: 66 months and 10 days ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Dr. Steven A. Rosenberg
Organization: National Cancer Institute
phone: 301-496-4164
e-mail: sar@mail.nih.gov


Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Steven Rosenberg, M.D., National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT00670748     History of Changes
Other Study ID Numbers: 080121
08-C-0121
Study First Received: May 1, 2008
Results First Received: May 19, 2016
Last Updated: October 26, 2016
Health Authority: United States: Federal Government
United States: Food and Drug Administration