Trial Outcomes & Findings for Aldesleukin With or Without Vaccine Therapy in Treating Patients With Stage IV Melanoma (NCT NCT00726739)

Last Updated: 2017-12-28

Results Overview

Progression free survival (PFS) was measured in months from date of randomization to date of disease progression, or date of death. For patients who died without tumor progression, PFS assumes their deaths are randomly related to tumor progression. Therefore, PFS includes deaths if they came first.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

21 participants

Primary outcome timeframe

From Date of Randomization to Date of Disease Progression or Last Contact - up to 2 years.

Results posted on

2017-12-28

Participant Flow

All patients were evaluated for eligibility by one of the investigators prior to enrollment.

This study requires concurrent registration to the University of Minnesota study "MT1999-06: Vaccination with Tetanus Toxoid and Keyhole Limpet Hemocyanin (KLH) to Assess Antigen-Specific Immune Responses" (IRB # 9904M01581, CPRC #2002LS032).

Participant milestones

Participant milestones
Measure	Arm I and III Crossover Group - LMI + Aldesleukin Patients receive allogeneic large multivalent immunogen melanoma vaccine (LMI) LP2307 intradermally on day 1 and aldesleukin subcutaneously (SC) on days 7 and 8. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Includes 6 patients who progressed and "crossed over" from Arm II.	Arm II (Control) - Aldesleukin Patients receive aldesleukin SC on days 1 and 2. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over and receive treatment on Arm I.
Overall Study STARTED	11	10
Overall Study COMPLETED	10	10
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Aldesleukin With or Without Vaccine Therapy in Treating Patients With Stage IV Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I and III Crossover Group - LMI + Aldesleukin n=11 Participants Includes 6 patients who progressed and "crossed over" from Arm II.	Arm II (Control) - Aldesleukin n=10 Participants Patients receive aldesleukin SC on days 1 and 2. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over and receive treatment on Arm I.	Total n=21 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	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Age, Continuous	63.8 years STANDARD_DEVIATION 11.4 • n=5 Participants	64.0 years STANDARD_DEVIATION 14.9 • n=7 Participants	63.9 years STANDARD_DEVIATION 12.8 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Region of Enrollment United States	11 participants n=5 Participants	10 participants n=7 Participants	21 participants n=5 Participants

PRIMARY outcome

Timeframe: From Date of Randomization to Date of Disease Progression or Last Contact - up to 2 years.

Population: All patients who received at least one dose of study treatment are included. One patient who was originally screened and randomized did not receive treatment due to brain metastasis. This patient was included in PFS analysis based on the intent-to-treat principle, but was excluded from the evaluation of adverse events.

Outcome measures

Outcome measures
Measure	Arm I and III Crossover Group - LMI + Aldesleukin n=11 Participants Patients receive allogeneic large multivalent immunogen melanoma vaccine (LMI) LP2307 intradermally on day 1 and aldesleukin subcutaneously (SC) on days 7 and 8. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Includes 6 patients who progressed and "crossed over" from Arm II.	Arm II (Control) - Aldesleukin n=10 Participants Patients receive aldesleukin SC on days 1 and 2. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over and receive treatment on Arm I.
Median Time of Progression-free Survival	2.20 Months Interval 0.03 to 4.07	1.95 Months Interval 0.95 to 20.6

SECONDARY outcome

Timeframe: Month 2 through Month 12

Population: All patients who received at least one dose of study treatment are included. One patient who was originally screened did not receive treatment due to brain metastasis.

Beginning at 2 months Through End of Treatment: To determine clinical response of each treatment group - Best Clinical response will be determined using Solid Tumor Response Criteria (RECIST). Complete Response (CR) = complete disappearance of all target lesions. Partial Response (PR) = At least a 30% decrease in sum of longest diameters of target lesions. Progressive Disease (PD) = At least a 20% increase in sum of longest diameters of target lesions. Stable Disease (SD) = Neither sufficient shrinkage to qualify for PR or PD.

Outcome measures

Outcome measures
Measure	Arm I and III Crossover Group - LMI + Aldesleukin n=11 Participants Patients receive allogeneic large multivalent immunogen melanoma vaccine (LMI) LP2307 intradermally on day 1 and aldesleukin subcutaneously (SC) on days 7 and 8. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Includes 6 patients who progressed and "crossed over" from Arm II.	Arm II (Control) - Aldesleukin n=10 Participants Patients receive aldesleukin SC on days 1 and 2. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over and receive treatment on Arm I.
Clinical Response of Lesion(s) Complete Response (CR)	0 participants	1 participants
Clinical Response of Lesion(s) Partial Response (PR)	0 participants	0 participants
Clinical Response of Lesion(s) Stable Disease (SD)	2 participants	1 participants
Clinical Response of Lesion(s) Progressive Disease (PD)	8 participants	8 participants
Clinical Response of Lesion(s) Missing information	1 participants	0 participants

SECONDARY outcome

Timeframe: 2 Years

Two year survival (alive at 2 years from randomization) rate of each treatment group.

Outcome measures

Outcome measures
Measure	Arm I and III Crossover Group - LMI + Aldesleukin n=11 Participants Patients receive allogeneic large multivalent immunogen melanoma vaccine (LMI) LP2307 intradermally on day 1 and aldesleukin subcutaneously (SC) on days 7 and 8. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Includes 6 patients who progressed and "crossed over" from Arm II.	Arm II (Control) - Aldesleukin n=10 Participants Patients receive aldesleukin SC on days 1 and 2. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over and receive treatment on Arm I.
Overall Survival at 2 Years	24 percentage of patients	27 percentage of patients

SECONDARY outcome

Timeframe: 1 Year

One year survival (alive at 1 year from randomization) rate of each treatment group.

Outcome measures

Outcome measures
Measure	Arm I and III Crossover Group - LMI + Aldesleukin n=11 Participants Patients receive allogeneic large multivalent immunogen melanoma vaccine (LMI) LP2307 intradermally on day 1 and aldesleukin subcutaneously (SC) on days 7 and 8. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Includes 6 patients who progressed and "crossed over" from Arm II.	Arm II (Control) - Aldesleukin n=10 Participants Patients receive aldesleukin SC on days 1 and 2. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over and receive treatment on Arm I.
Overall Survival at 1 Year	45 Percentage of patients	40 Percentage of patients

SECONDARY outcome

Timeframe: 48 hours After Study Medication

Immune responses is be assessed by Delayed Type Hypersensitive (DTH) responses to LMI, IFN-γ production by CD8 T cells using the ELISPOT assay, and CD8 T cell binding to HLA-A2 multimers complexed with melanoma-derived peptides (pentamer analysis). DTH reactions are determined at 48 hours by measuring the largest diameter and right angle diameter of the area of induration and calculating the mean. DTH responses are recorded as present or absent but cannot be used as a quantitative measure of immune activation.

Outcome measures

Outcome measures
Measure	Arm I and III Crossover Group - LMI + Aldesleukin n=11 Participants Patients receive allogeneic large multivalent immunogen melanoma vaccine (LMI) LP2307 intradermally on day 1 and aldesleukin subcutaneously (SC) on days 7 and 8. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Includes 6 patients who progressed and "crossed over" from Arm II.	Arm II (Control) - Aldesleukin n=10 Participants Patients receive aldesleukin SC on days 1 and 2. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over and receive treatment on Arm I.
Immune Response KLH twofold responder	5 participants	8 participants
Immune Response KLH tenfold responder	2 participants	7 participants
Immune Response Missing information	1 participants	0 participants

Adverse Events

Arm I and III Crossover Group - LMI + Aldesleukin

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Arm II (Control) - Aldesleukin

Serious events: 3 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Arm I and III Crossover Group - LMI + Aldesleukin n=10 participants at risk Patients receive allogeneic large multivalent immunogen melanoma vaccine (LMI) LP2307 intradermally on day 1 and aldesleukin subcutaneously (SC) on days 7 and 8. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Includes 6 patients who progressed and "crossed over" from Arm II.	Arm II (Control) - Aldesleukin n=10 participants at risk Patients receive aldesleukin SC on days 1 and 2. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over and receive treatment on arm I.
Cardiac disorders Atrial fibrillation	0.00% 0/10 • Adverse events were followed for 28 days (+/- 14 day) after last dose of study drug, an average of 1 year. One patient withdrew after randomization and before LMI (large multivalent immunogen) +IL2 (aldesleukin) started and was excluded from the evaluation of toxicity (Arm I group).	10.0% 1/10 • Number of events 1 • Adverse events were followed for 28 days (+/- 14 day) after last dose of study drug, an average of 1 year. One patient withdrew after randomization and before LMI (large multivalent immunogen) +IL2 (aldesleukin) started and was excluded from the evaluation of toxicity (Arm I group).
Gastrointestinal disorders Dehydration	10.0% 1/10 • Number of events 1 • Adverse events were followed for 28 days (+/- 14 day) after last dose of study drug, an average of 1 year. One patient withdrew after randomization and before LMI (large multivalent immunogen) +IL2 (aldesleukin) started and was excluded from the evaluation of toxicity (Arm I group).	0.00% 0/10 • Adverse events were followed for 28 days (+/- 14 day) after last dose of study drug, an average of 1 year. One patient withdrew after randomization and before LMI (large multivalent immunogen) +IL2 (aldesleukin) started and was excluded from the evaluation of toxicity (Arm I group).
General disorders Pain - back	10.0% 1/10 • Number of events 1 • Adverse events were followed for 28 days (+/- 14 day) after last dose of study drug, an average of 1 year. One patient withdrew after randomization and before LMI (large multivalent immunogen) +IL2 (aldesleukin) started and was excluded from the evaluation of toxicity (Arm I group).	0.00% 0/10 • Adverse events were followed for 28 days (+/- 14 day) after last dose of study drug, an average of 1 year. One patient withdrew after randomization and before LMI (large multivalent immunogen) +IL2 (aldesleukin) started and was excluded from the evaluation of toxicity (Arm I group).
Gastrointestinal disorders Progressive Disease	0.00% 0/10 • Adverse events were followed for 28 days (+/- 14 day) after last dose of study drug, an average of 1 year. One patient withdrew after randomization and before LMI (large multivalent immunogen) +IL2 (aldesleukin) started and was excluded from the evaluation of toxicity (Arm I group).	10.0% 1/10 • Number of events 1 • Adverse events were followed for 28 days (+/- 14 day) after last dose of study drug, an average of 1 year. One patient withdrew after randomization and before LMI (large multivalent immunogen) +IL2 (aldesleukin) started and was excluded from the evaluation of toxicity (Arm I group).
Respiratory, thoracic and mediastinal disorders Hemorrhage	0.00% 0/10 • Adverse events were followed for 28 days (+/- 14 day) after last dose of study drug, an average of 1 year. One patient withdrew after randomization and before LMI (large multivalent immunogen) +IL2 (aldesleukin) started and was excluded from the evaluation of toxicity (Arm I group).	10.0% 1/10 • Number of events 1 • Adverse events were followed for 28 days (+/- 14 day) after last dose of study drug, an average of 1 year. One patient withdrew after randomization and before LMI (large multivalent immunogen) +IL2 (aldesleukin) started and was excluded from the evaluation of toxicity (Arm I group).
Cardiac disorders Hypotension	10.0% 1/10 • Number of events 1 • Adverse events were followed for 28 days (+/- 14 day) after last dose of study drug, an average of 1 year. One patient withdrew after randomization and before LMI (large multivalent immunogen) +IL2 (aldesleukin) started and was excluded from the evaluation of toxicity (Arm I group).	0.00% 0/10 • Adverse events were followed for 28 days (+/- 14 day) after last dose of study drug, an average of 1 year. One patient withdrew after randomization and before LMI (large multivalent immunogen) +IL2 (aldesleukin) started and was excluded from the evaluation of toxicity (Arm I group).

Other adverse events

Additional Information

Arkadiusz Dudek, M.D.

Masonic Cancer Center, University of Minnesota

Phone: 612-624-0123

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place