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CTLA-4 Blockade and Low Dose Cyclophosphamide in Patients With Advanced Malignant Melanoma

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ClinicalTrials.gov Identifier: NCT01740401
Recruitment Status : Terminated (Primary Endpoint not met)
First Posted : December 4, 2012
Results First Posted : April 26, 2017
Last Update Posted : December 6, 2017
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Nina Bhardwaj, Icahn School of Medicine at Mount Sinai

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Melanoma
Intervention Drug: Cyclophosphamide
Enrollment 10
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Cyclophosphamide, Ipilimumab
Hide Arm/Group Description

Treatment:

Cyclophosphamide 300 mg/m^2 po - Day 1 of Weeks 1, 4, 7, and 10, for a total of 4 doses; (premedication prior to each dose of Cyclophosphamide 8mg Zofran po, then prn)

Ipilimumab 10 mg/kg iv - Day 3 of Weeks 1, 4, 7, and 10 for a total of 4 doses Maintenance treatment will be given on Weeks 24, 36, and 48 Ipilimumab 10 mg/kg iv

Cyclophosphamide, Ipilimumab: This study consists of a Treatment Period, D1 Zofran 8mg pre-Cyclophosphamide 300mg/mg2 po and D3 Ipilimumab 10mg/kg iv wks 1,4,7 and 10; Tumor assessment at week 12; Follow-Up period weeks 13,16,and 20 with no treatment; Maintenance Period, D1 10mg/kg iv wks 24,36,48 and 60. Week 40=end of treatment; week 60=end of study

Period Title: Overall Study
Started 10
Completed 0
Not Completed 10
Reason Not Completed
Progression of disease             6
Adverse Event             2
Did not reach primary endpoint             2
Arm/Group Title Cyclophosphamide, Ipilimumab
Hide Arm/Group Description

Treatment:

Cyclophosphamide 300 mg/m^2 po - Day 1 of Weeks 1, 4, 7, and 10, for a total of 4 doses; (premedication prior to each dose of Cyclophosphamide 8mg Zofran po, then prn)

Ipilimumab 10 mg/kg iv - Day 3 of Weeks 1, 4, 7, and 10 for a total of 4 doses Maintenance treatment will be given on Weeks 24, 36, and 48 Ipilimumab 10 mg/kg iv

Cyclophosphamide, Ipilimumab: This study consists of a Treatment Period, D1 Zofran 8mg pre-Cyclophosphamide 300mg/mg2 po and D3 Ipilimumab 10mg/kg iv wks 1,4,7 and 10; Tumor assessment at week 12; Follow-Up period weeks 13,16,and 20 with no treatment; Maintenance Period, D1 10mg/kg iv wks 24,36,48 and 60. Week 40=end of treatment; week 60=end of study

Overall Number of Baseline Participants 10
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 10 participants
59
(36 to 75)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
Female
2
  20.0%
Male
8
  80.0%
Malignant Melanoma (MM) site  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
Cutaneous MM
7
  70.0%
Ocular MM
2
  20.0%
Unknown Primary MM
1
  10.0%
1.Primary Outcome
Title The Anti-tumor Activity of the Combination of Low Dose Cyclophosphamide and CTLA-4 Blockade Using Objective Response Rate (ORR)
Hide Description Objective response rate (ORR) using mWHO RC. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cyclophosphamide, Ipilimumab
Hide Arm/Group Description:

Treatment:

Cyclophosphamide 300 mg/m^2 po - Day 1 of Weeks 1, 4, 7, and 10, for a total of 4 doses; (premedication prior to each dose of Cyclophosphamide 8mg Zofran po, then prn)

Ipilimumab 10 mg/kg iv - Day 3 of Weeks 1, 4, 7, and 10 for a total of 4 doses Maintenance treatment will be given on Weeks 24, 36, and 48 Ipilimumab 10 mg/kg iv

Cyclophosphamide, Ipilimumab: This study consists of a Treatment Period, D1 Zofran 8mg pre-Cyclophosphamide 300mg/mg2 po and D3 Ipilimumab 10mg/kg iv wks 1,4,7 and 10; Tumor assessment at week 12; Follow-Up period weeks 13,16,and 20 with no treatment; Maintenance Period, D1 10mg/kg iv wks 24,36,48 and 60. Week 40=end of treatment; week 60=end of study

Overall Number of Participants Analyzed 10
Measure Type: Count of Participants
Unit of Measure: Participants
Stable disease
4
  40.0%
Progression of disease
6
  60.0%
2.Secondary Outcome
Title Progression-free Survival
Hide Description Progression-free survival is measured from date of entry to date of 1st documented evidence of recurrence, confirmation of PD, or death (whichever is 1st). T regulatory cells are measured on D1 (pre CTX) & D3 of each cycle.
Time Frame Week 60
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Endpoint not met, study terminated, data not collected
Arm/Group Title Cyclophosphamide, Ipilimumab
Hide Arm/Group Description:

Treatment:

Cyclophosphamide 300 mg/m^2 po - Day 1 of Weeks 1, 4, 7, and 10, for a total of 4 doses; (premedication prior to each dose of Cyclophosphamide 8mg Zofran po, then prn)

Ipilimumab 10 mg/kg iv - Day 3 of Weeks 1, 4, 7, and 10 for a total of 4 doses Maintenance treatment will be given on Weeks 24, 36, and 48 Ipilimumab 10 mg/kg iv

Cyclophosphamide, Ipilimumab: This study consists of a Treatment Period, D1 Zofran 8mg pre-Cyclophosphamide 300mg/mg2 po and D3 Ipilimumab 10mg/kg iv wks 1,4,7 and 10; Tumor assessment at week 12; Follow-Up period weeks 13,16,and 20 with no treatment; Maintenance Period, D1 10mg/kg iv wks 24,36,48 and 60. Week 40=end of treatment; week 60=end of study

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title T Regulatory Cell Profile in Peripheral Blood
Hide Description Peripheral blood taken at baseline/various therapeutic time points/possibly maintenance cycles to evaluate T regulatory cells identified, serially monitored by polychromatic flow cytometry using FoxP3+/CD4+/CD127low/CD25hi markers.
Time Frame Week 60
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Endpoint not met, study terminated, data not collected
Arm/Group Title Cyclophosphamide, Ipilimumab
Hide Arm/Group Description:

Treatment:

Cyclophosphamide 300 mg/m^2 po - Day 1 of Weeks 1, 4, 7, and 10, for a total of 4 doses; (premedication prior to each dose of Cyclophosphamide 8mg Zofran po, then prn)

Ipilimumab 10 mg/kg iv - Day 3 of Weeks 1, 4, 7, and 10 for a total of 4 doses Maintenance treatment will be given on Weeks 24, 36, and 48 Ipilimumab 10 mg/kg iv

Cyclophosphamide, Ipilimumab: This study consists of a Treatment Period, D1 Zofran 8mg pre-Cyclophosphamide 300mg/mg2 po and D3 Ipilimumab 10mg/kg iv wks 1,4,7 and 10; Tumor assessment at week 12; Follow-Up period weeks 13,16,and 20 with no treatment; Maintenance Period, D1 10mg/kg iv wks 24,36,48 and 60. Week 40=end of treatment; week 60=end of study

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
4.Other Pre-specified Outcome
Title Tumor-specific T Cell Responses Will be Measured in a Subset of Patients Who Have Biopsy Accessible Tumor and Have Tumor Biopsies Taken.
Hide Description One of the tumor punch biopsy will be put in formalin for paraffin-embedding. The other tumor punch biopsy will be processed to obtain lysates to be used as antigens for the T cell assays. Two tumor punch biopsies (4mm in diameter) will be obtained before and after therapy (baseline and week 12, and optional during weeks 24, 36, and 48) if patients have accessible tumors.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Endpoint not met, study terminated, data not collected
Arm/Group Title Cyclophosphamide, Ipilimumab
Hide Arm/Group Description:

Treatment:

Cyclophosphamide 300 mg/m^2 po - Day 1 of Weeks 1, 4, 7, and 10, for a total of 4 doses; (premedication prior to each dose of Cyclophosphamide 8mg Zofran po, then prn)

Ipilimumab 10 mg/kg iv - Day 3 of Weeks 1, 4, 7, and 10 for a total of 4 doses Maintenance treatment will be given on Weeks 24, 36, and 48 Ipilimumab 10 mg/kg iv

Cyclophosphamide, Ipilimumab: This study consists of a Treatment Period, D1 Zofran 8mg pre-Cyclophosphamide 300mg/mg2 po and D3 Ipilimumab 10mg/kg iv wks 1,4,7 and 10; Tumor assessment at week 12; Follow-Up period weeks 13,16,and 20 with no treatment; Maintenance Period, D1 10mg/kg iv wks 24,36,48 and 60. Week 40=end of treatment; week 60=end of study

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cyclophosphamide, Ipilimumab
Hide Arm/Group Description

Treatment:

Cyclophosphamide 300 mg/m^2 po - Day 1 of Weeks 1, 4, 7, and 10, for a total of 4 doses; (premedication prior to each dose of Cyclophosphamide 8mg Zofran po, then prn)

Ipilimumab 10 mg/kg iv - Day 3 of Weeks 1, 4, 7, and 10 for a total of 4 doses Maintenance treatment will be given on Weeks 24, 36, and 48 Ipilimumab 10 mg/kg iv

Cyclophosphamide, Ipilimumab: This study consists of a Treatment Period, D1 Zofran 8mg pre-Cyclophosphamide 300mg/mg2 po and D3 Ipilimuab 10mg/kg iv wks 1,4,7 and 10; Tumor assessment at week 12; Follow-Up period weeks 13,16,and 20 with no treatment; Maintenance Period, D1 10mg/kg iv wks 24,36,48 and 60. Week 40=end of treatment; week 60=end of study

All-Cause Mortality
Cyclophosphamide, Ipilimumab
Affected / at Risk (%)
Total   0/10 (0.00%) 
Hide Serious Adverse Events
Cyclophosphamide, Ipilimumab
Affected / at Risk (%)
Total   4/10 (40.00%) 
Blood and lymphatic system disorders   
Thromboembolic event  1/10 (10.00%) 
Endocrine disorders   
Hypothyroidism  1/10 (10.00%) 
Gastrointestinal disorders   
Diarrhea  2/10 (20.00%) 
Hepatobiliary disorders   
Lipase elevation  1/10 (10.00%) 
Amylase elevation  1/10 (10.00%) 
1
Term from vocabulary, CTCAE (4.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Cyclophosphamide, Ipilimumab
Affected / at Risk (%)
Total   7/10 (70.00%) 
Gastrointestinal disorders   
Abdominal cramping  1/10 (10.00%) 
Diarrhea  1/10 (10.00%) 
General disorders   
Anorexia  1/10 (10.00%) 
Fatigue  4/10 (40.00%) 
Nausea  3/10 (30.00%) 
Nasal congestion  2/10 (20.00%) 
Musculoskeletal and connective tissue disorders   
Lower back discomfort  1/10 (10.00%) 
Nervous system disorders   
Pain  1/10 (10.00%) 
Skin and subcutaneous tissue disorders   
Depigmentation  2/10 (20.00%) 
Erythemia  1/10 (10.00%) 
Pruritus  2/10 (20.00%) 
1
Term from vocabulary, CTCAE (4.0)
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Nina Bhardwaj
Organization: Icahn School of Medicine at Mount Sinai
Phone: 212-824-8427
EMail: nina.bhardwaj@mssm.edu
Layout table for additonal information
Responsible Party: Nina Bhardwaj, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT01740401    
Other Study ID Numbers: GCO 14-0677
114660 ( Other Identifier: CA184-061 )
First Submitted: November 29, 2012
First Posted: December 4, 2012
Results First Submitted: March 15, 2017
Results First Posted: April 26, 2017
Last Update Posted: December 6, 2017