Trial Outcomes & Findings for HD IL-2 + Ipilimumab in Patients With Metastatic Melanoma (NCT NCT01856023)

Last Updated: 2023-12-05

Results Overview

evaluable patients who received at least 50% of both research drugs and had their disease re-evaluated after baseline; defined in days for the start of the first treatment to death. percent of patients alive at 1 year; estimates were assessed using Kaplan-Meier method for the entire subject population for each treatment arm separately.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

29 participants

Primary outcome timeframe

start of first treatment to date of death from any cause and patients alive at their last evaluation date were censored up to 1 year.

Results posted on

2023-12-05

Participant Flow

Study initiation Sept 11, 2013 - Early Study Termination August 18, 2015 Planned accrual 50 pts/ arm.

Patients will be randomized to receive both treatments in different sequence: Arm 1 IL-2 followed by Ipi; Arm 2 IPI followed by IL-2 Evaluable Patients will have received at least 50% of dose of both study drugs and completed assessment; Safety Population are all patients who received 1 dose of either study drug; Intent to treat

Participant milestones

Participant milestones
Measure	Treatment Arm 1 HD IL-2 1st Followed by Ipilimumab Patients will receive two courses (four cycles) of High Dose Interleukin-2 (HD IL-2) followed by one course (four doses) of ipilimumab. 3-6 week interval between the two drugs to allow resolution of treatment-related toxicities. High Dose Interleukin-600,000IU/kg IV every 8 hours up to 14 doses per cycle Ipilimumab 3mg/kg IV every 3 weeks up to 4 doses	Treatment Arm 2 Ipilimumab 1st Followed by HD IL-2 Patients will receive one course (four doses) of ipilimumab followed by two courses (four cycles) of HD IL-2. 3-6 week interval between the two drugs to allow resolution of treatment-related toxicities. High Dose Interleukin-600,000IU/kg IV every 8 hours up to 14 doses per cycle Ipilimumab 3mg/kg IV every 3 weeks up to 4 doses
Overall Study STARTED	13	16
Overall Study Intent to Treat: Received One Dose of Study Drug	12	16
Overall Study Evaluable: Received 50% of Each Study Drug	8	10
Overall Study COMPLETED	3	4
Overall Study NOT COMPLETED	10	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment Arm 1 HD IL-2 1st Followed by Ipilimumab Patients will receive two courses (four cycles) of High Dose Interleukin-2 (HD IL-2) followed by one course (four doses) of ipilimumab. 3-6 week interval between the two drugs to allow resolution of treatment-related toxicities. High Dose Interleukin-600,000IU/kg IV every 8 hours up to 14 doses per cycle Ipilimumab 3mg/kg IV every 3 weeks up to 4 doses	Treatment Arm 2 Ipilimumab 1st Followed by HD IL-2 Patients will receive one course (four doses) of ipilimumab followed by two courses (four cycles) of HD IL-2. 3-6 week interval between the two drugs to allow resolution of treatment-related toxicities. High Dose Interleukin-600,000IU/kg IV every 8 hours up to 14 doses per cycle Ipilimumab 3mg/kg IV every 3 weeks up to 4 doses
Overall Study Death	1	2
Overall Study Adverse Event	2	1
Overall Study Lack of Efficacy	5	5
Overall Study non compliance, study closure	1	3
Overall Study Withdrawal by Subject	1	1

Baseline Characteristics

HD IL-2 + Ipilimumab in Patients With Metastatic Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment Arm 1 IL-2 First n=13 Participants Patients will receive two courses (four cycles) of High Dose Interleukin-2 (HD IL-2) followed by one course (four doses) of ipilimumab. High Dose Interleukin-2 Ipilimumab	Treatment Arm 2 Ipi First n=16 Participants Patients will receive one course (four doses) of ipilimumab followed by two courses (four cycles) of HD IL-2. High Dose Interleukin-2 Ipilimumab	Total n=29 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants	14 Participants n=7 Participants	26 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Age, Continuous	49.5 years n=5 Participants	46 years n=7 Participants	48 years n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	12 Participants n=7 Participants	20 Participants n=5 Participants
Region of Enrollment United States	13 participants n=5 Participants	16 participants n=7 Participants	29 participants n=5 Participants

PRIMARY outcome

Timeframe: start of first treatment to date of death from any cause and patients alive at their last evaluation date were censored up to 1 year.

Population: patients who received at least 50% of both research drugs as planned-and had their disease re-evaluated after baseline; patients who exhibited PD or died before the end of one course of treatment were also considered evaluable

Outcome measures

Outcome measures
Measure	Treatment Arm 1 n=8 Participants Patients will receive 2 courses (four cycles) of High Dose Interleukin-2 (HD IL-2) followed by one course (four doses) of ipilimumab. 3-6 week interval between the two drugs administered to resolve treatment-related toxicities	Treatment Arm 2 n=10 Participants Patients will receive one course (four doses) of ipilimumab followed by two courses (four cycles) of HD IL-2. 3-6 week interval between the two drugs administered to resolve treatment-related toxicities
Estimated One-year OS in the Evaluable Population in Each Treatment Arm Separately	73 percentage of participants Interval 38.0 to 91.0	75 percentage of participants Interval 40.0 to 92.0

SECONDARY outcome

Timeframe: 5-11 weeks, 13-19 Weeks, 24-30 weeks and 1 year

Population: Evaluable patients who received up to 50% of the planned cycles of therapy in both study drugs; comparison of the sequences of therapy between treatment arms

duration of time (in Days) from start of the first treatment to the time of objective disease progression or death at one year. The immune-related response criteria (irRC) determined based on tumor burden calculated on the WHO method of multiplying the perpendicular dimensions of all lesions are summed to obtain the tumor burden. The total tumor burden + SPD (index lesions) + SPD (new measurable lesions) Based on CT scans and Physical exam at designated timepoints. CR- Disappearance of all known disease; PR\>/equal to decrease; SD Neither CR or PD; PD 25%increase; new lesion.

Outcome measures

Outcome measures
Measure	Treatment Arm 1 n=8 Participants Patients will receive 2 courses (four cycles) of High Dose Interleukin-2 (HD IL-2) followed by one course (four doses) of ipilimumab. 3-6 week interval between the two drugs administered to resolve treatment-related toxicities	Treatment Arm 2 n=10 Participants Patients will receive one course (four doses) of ipilimumab followed by two courses (four cycles) of HD IL-2. 3-6 week interval between the two drugs administered to resolve treatment-related toxicities
Progression-free Survival	58 days Interval 18.0 to 84.0	80 days Interval 41.0 to 95.0

Adverse Events

Treatment Arm 1 HD IL-2 Administered 1st Followed by Ipilimumab

Serious events: 9 serious events

Other events: 9 other events

Deaths: 1 deaths

Treatment Arm 2 Ipilimumab Administered 1st Followed by HD IL-2

Serious events: 10 serious events

Other events: 10 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Head of Medical Affairs

Clinigen

Phone: 8323263256

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Treatment Arm 1 HD IL-2 Administered 1st Followed by Ipilimumab n=13 participants at risk Patients will receive two courses (four cycles) of High Dose Interleukin-2 (HD IL-2) followed by one course (four doses) of ipilimumab. 3-6 week interval between the two drugs to allow resolution of treatment-related toxicities. High Dose Interleukin-600,000IU/kg IV every 8 hours up to 14 doses per cycle Ipilimumab 3mg/kg IV every 3 weeks up to 4 doses	Treatment Arm 2 Ipilimumab Administered 1st Followed by HD IL-2 n=16 participants at risk Patients will receive one course (four doses) of ipilimumab followed by two courses (four cycles) of HD IL-2. 3-6 week interval between the two drugs to allow resolution of treatment-related toxicities. High Dose Interleukin-600,000IU/kg IV every 8 hours up to 14 doses per cycle Ipilimumab 3mg/kg IV every 3 weeks up to 4 doses
Gastrointestinal disorders Diarrhea	7.7% 1/13 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.	0.00% 0/16 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.
Gastrointestinal disorders colitis	0.00% 0/13 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.	12.5% 2/16 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.
Gastrointestinal disorders ascites	0.00% 0/13 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.	6.2% 1/16 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.
Gastrointestinal disorders intestinal perforation	0.00% 0/13 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.	6.2% 1/16 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.
Musculoskeletal and connective tissue disorders back pain, neck pain	7.7% 1/13 • Number of events 2 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.	0.00% 0/16 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.
Cardiac disorders supraventricular tachycardia, ventricular tachycardia	15.4% 2/13 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.	0.00% 0/16 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.
Nervous system disorders Autoimmune encephalitis, intracranial Hemorrhage	15.4% 2/13 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.	0.00% 0/16 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.
Psychiatric disorders Sedation, mental Status change	0.00% 0/13 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.	6.2% 1/16 • Number of events 2 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.
Infections and infestations Pneumonia	0.00% 0/13 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.	12.5% 2/16 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.
Infections and infestations Perihepatic Abscess	0.00% 0/13 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.	6.2% 1/16 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.
Respiratory, thoracic and mediastinal disorders Respiratory Failure, Hypoxia	7.7% 1/13 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.	12.5% 2/16 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.
Blood and lymphatic system disorders Thrombocytopenia	7.7% 1/13 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.	0.00% 0/16 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.
Renal and urinary disorders renal failure acute	0.00% 0/13 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.	6.2% 1/16 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.
Reproductive system and breast disorders Female genital tract fistula	0.00% 0/13 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.	6.2% 1/16 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.
Vascular disorders embolism	7.7% 1/13 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.	0.00% 0/16 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.
Infections and infestations wound infection	7.7% 1/13 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.	0.00% 0/16 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.
Infections and infestations Pyelonephritis	7.7% 1/13 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.	0.00% 0/16 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.
Musculoskeletal and connective tissue disorders Muscular Weakness	7.7% 1/13 • Number of events 2 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.	0.00% 0/16 • Adverse events were monitored/ assessed for up to 30 weeks after 1st dose of study drug. All -cause mortality monitored/assessed up to 1 year. AEs and SAEs listed as described below by arm and not specific for each drug. Adverse events were not assessed separately for each drug; However, side effects of each drug are established and commented in the final manuscript.