Phase 2 Study of Ipilimumab in Children and Adolescents (12 to < 18 Years) With Previously Treated or Untreated, Unresectable Stage III or Stage lV Malignant Melanoma

Phase 2 Study of Ipilimumab in Children and Adolescents (12 to < 18 Years) With Previously Treated or Untreated, Unresectable Stage III or Stage IV Malignant Melanoma

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01696045

Enrollment

Registered

2012-09-28

Start date

2012-11-12

Completion date

2016-07-31

Last updated

2017-08-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Malignant Melanoma

Brief summary

The purpose of the study is to comply with the Pediatric Investigation Plan requirements of Ipilimumab

Interventions

BIOLOGICALIpilimumab

Study design

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

12 Years to 17 Years

Healthy volunteers

Inclusion criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. Inclusion Criteria: * 12 \< 18 years of age * Previously treated or untreated, unresectable Stage III or Stage IV malignant melanoma * Karnofsky Performance Status (KPS) or Lansky Score ≥ 50

Exclusion criteria

* Primary Ocular Melanoma * Prior therapy with a Cytotoxic T Lymphocyte Antigen 4 (CTLA-4) or Programmed death- 1 (PD-1) antagonist, or Programmed cell death- ligand 1 (PD-L1) or CD137 agonists * Symptomatic brain metastases * History of autoimmune diseases

Design outcomes

Primary

Measure	Time frame	Description
Overall Survival (OS) Rate at 1 Year	1 year following start of treatment (Assessed up to June 2016, approximately 38 months)	Overall Survival (OS) was defined as the time from the start of ipilimumab treatment date to death due to any cause. If a participant had not died, the participant was censored at the time of last contact (last known alive date). OS rates at 1 year were calculated from both Kaplan-Meier estimates and the proportion of participants alive at 1 year following start of treatment.
Percentage of Participants With Severe Immune-Mediated Adverse Reactions (imARs)	From first dose to 90 days after last dose (Assessed up to June 2016, approximately 38 months)	The percentage of participants with severe Immune-mediated Adverse Reactions (imARs) was determined by dividing the number of participants with grade 3 or worse imARs by the total number of treated participants and expressing this number as a percentage. imARs were AEs determined by the investigator to have an immune-mediated etiology, including inflammatory events associated with ipilimumab treatment.

Secondary

Measure	Time frame	Description
Disease Control Rate (DCR)	From Day 1 of first subject, first treatment to Day 365 of last subject, first treatment (approximately 36 months)	Disease control rate was defined as the percentage of all treated participants with a best overall response of Complete Response (CR), Partial Response (PR), or Stable disease (SD), based on the investigator's assessment per mWHO Criteria. CR= Complete disappearance of all non-index lesions. PR= Decrease, relative to baseline, of 50% or greater in the sum of the products of the two largest perpendicular diameters of all index lesions. SD= Does not meet criteria for complete or partial response, in the absence of progressive disease. PD= At least 25% increase in the sum of the products of all index lesions (taking as reference the smallest sum recorded at or following baseline) and/or the appearance of any new lesion(s).
Progression Free Survival	From date of first treatment until disease progression or death (Assessed up to June 2016, approximately 38 months)	Progression-Free Survival was defined as the time from the start of ipilimumab treatment to disease progression or death, whichever occurs first. A participant who died without reported progression was considered to have progressed on their date of death. For participants who remained alive and had not progressed, PFS was censored on the date of the last tumor assessment.
Best Overall Response Rate (BORR)	From Day 1 of first subject, first treatment to Day 365 of last subject, first treatment (approximately 36 months)	Best Overall Response Rate (BORR) was defined as the total number of participants with the best overall response of Complete Response (CR) or Partial Response (PR) divided by the total number of treated participants and expressed as a percentage. CR= Complete disappearance of all non-index lesions. PR= Decrease, relative to baseline, of 50% or greater in the sum of the products of the two largest perpendicular diameters of all index lesions. SD= Does not meet criteria for complete or partial response, in the absence of progressive disease. PD= At least 25% increase in the sum of the products of all index lesions (taking as reference the smallest sum recorded at or following baseline) and/or the appearance of any new lesion(s).
Overall Survival Time	From date of first treatment to date of death (Assessed up to June 2016, approximately 38 months)	Overall Survival time was defined as the time from the start of ipilimumab treatment date to date of death due to any cause. Participants who had not died were censored at the time of last contact (last known alive date).

Countries

Belgium, Denmark, France, Germany, Mexico, Spain, United Kingdom, United States

Participant flow

Pre-assignment details

14 participants were enrolled in the study. 12 participants received study treatment. 2 participants were enrolled and not treated because they no longer met study criteria.

Participants by arm

Arm	Count
Ipilimumab 3mg/kg Ipilimumab was administered intravenously (IV) over 90 minutes on Day 1 of each 21-day cycle for 4 cycles.	4
Ipilimumab 10mg/kg Ipilimumab was administered intravenously (IV) over 90 minutes on Day 1 of each 21-day cycle for 4 cycles.	8
Total	12

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Disease progression	2	2
Overall Study	Study drug toxicity	1	5

Baseline characteristics

Characteristic	Ipilimumab 10mg/kg	Total	Ipilimumab 3mg/kg
Age, Continuous	14.9 years STANDARD_DEVIATION 0.64	14.3 years STANDARD_DEVIATION 1.37	13.3 years STANDARD_DEVIATION 1.89
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	8 Participants	11 Participants	3 Participants
Sex: Female, Male Female	3 Participants	5 Participants	2 Participants
Sex: Female, Male Male	5 Participants	7 Participants	2 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	4 / 4	8 / 8
serious Total, serious adverse events	1 / 4	6 / 8

Outcome results

Primary

Overall Survival (OS) Rate at 1 Year

Overall Survival (OS) was defined as the time from the start of ipilimumab treatment date to death due to any cause. If a participant had not died, the participant was censored at the time of last contact (last known alive date). OS rates at 1 year were calculated from both Kaplan-Meier estimates and the proportion of participants alive at 1 year following start of treatment.

Time frame: 1 year following start of treatment (Assessed up to June 2016, approximately 38 months)