Trial Outcomes & Findings for CTLA-4 Blockade and Low Dose Cyclophosphamide in Patients With Advanced Malignant Melanoma (NCT NCT01740401)

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

10 participants

Primary outcome timeframe

12 weeks

Results posted on

2017-12-06

Participant Flow

Participant milestones

Participant milestones
Measure	Cyclophosphamide, Ipilimumab 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 Study STARTED	10
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Cyclophosphamide, Ipilimumab 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 Study Progression of disease	6
Overall Study Adverse Event	2
Overall Study Did not reach primary endpoint	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cyclophosphamide, Ipilimumab n=10 Participants 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
Age, Continuous	59 years n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants
Malignant Melanoma (MM) site Cutaneous MM	7 Participants n=5 Participants
Malignant Melanoma (MM) site Ocular MM	2 Participants n=5 Participants
Malignant Melanoma (MM) site Unknown Primary MM	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

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.

Outcome measures

Outcome measures
Measure	Cyclophosphamide, Ipilimumab n=10 Participants 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
The Anti-tumor Activity of the Combination of Low Dose Cyclophosphamide and CTLA-4 Blockade Using Objective Response Rate (ORR) Stable disease	4 Participants
The Anti-tumor Activity of the Combination of Low Dose Cyclophosphamide and CTLA-4 Blockade Using Objective Response Rate (ORR) Progression of disease	6 Participants

SECONDARY outcome

Timeframe: Week 60

Population: Primary Endpoint not met, study terminated, data not collected

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 60

Population: Primary Endpoint not met, study terminated, data not collected

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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 48

Population: Primary Endpoint not met, study terminated, data not collected

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.

Outcome measures

Outcome data not reported

Adverse Events

Cyclophosphamide, Ipilimumab

Serious events: 4 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cyclophosphamide, Ipilimumab n=10 participants at risk 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
Hepatobiliary disorders Lipase elevation	10.0% 1/10
Hepatobiliary disorders Amylase elevation	10.0% 1/10
Gastrointestinal disorders Diarrhea	20.0% 2/10
Endocrine disorders Hypothyroidism	10.0% 1/10
Blood and lymphatic system disorders Thromboembolic event	10.0% 1/10

Other adverse events

Other adverse events
Measure	Cyclophosphamide, Ipilimumab n=10 participants at risk 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
General disorders Anorexia	10.0% 1/10
Gastrointestinal disorders Abdominal cramping	10.0% 1/10
Skin and subcutaneous tissue disorders Depigmentation	20.0% 2/10
Gastrointestinal disorders Diarrhea	10.0% 1/10
Musculoskeletal and connective tissue disorders Lower back discomfort	10.0% 1/10
Skin and subcutaneous tissue disorders Erythemia	10.0% 1/10
General disorders Fatigue	40.0% 4/10
General disorders Nausea	30.0% 3/10
General disorders Nasal congestion	20.0% 2/10
Nervous system disorders Pain	10.0% 1/10
Skin and subcutaneous tissue disorders Pruritus	20.0% 2/10

Additional Information

Dr. Nina Bhardwaj

Icahn School of Medicine at Mount Sinai

Phone: 212-824-8427

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place