Trial Outcomes & Findings for Open-label, Phase II Study of MLN9708 in Patients With Relapsed/Refractory Cutaneous and Peripheral T-cell Lymphomas (NCT NCT02158975)

Last Updated: 2017-11-13

Results Overview

The percentage of patients with an objective response rate will be determined. The overall response will be based on response in each compartment (skin, blood, lymph nodes and viscera) using a global composite scoring system. Objective response is considered (CR) Complete Response (Complete disappearance of all clinical evidence of disease), CRu (Complete Response Unconfirmed), or (PR) Partial Response (Regression of measurable disease).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

13 participants

Primary outcome timeframe

Up to 24 months after initiation of study treatment

Results posted on

2017-11-13

Participant Flow

Participant milestones

Participant milestones
Measure	MLN9708 MLN9708 4mg by mouth weekly (days 1, 8, 15) every 28 days. MLN9708
Overall Study STARTED	13
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	MLN9708 MLN9708 4mg by mouth weekly (days 1, 8, 15) every 28 days. MLN9708
Overall Study Did not complete 1 cycle nor > 1dose	1

Baseline Characteristics

Open-label, Phase II Study of MLN9708 in Patients With Relapsed/Refractory Cutaneous and Peripheral T-cell Lymphomas

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MLN9708 n=12 Participants MLN9708 4mg by mouth weekly (days 1, 8, 15) every 28 days. MLN9708
Age, Continuous	70 years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants
T-Cell Lymphoma Subtype Cutaneous T-cell Lymphoma (CTCL)	5 Participants n=5 Participants
T-Cell Lymphoma Subtype Peripheral T-cell Lymphoma (PTCL)	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 24 months after initiation of study treatment

Population: 12 analyzable patients

Outcome measures

Outcome measures
Measure	MLN9708 n=12 Participants MLN9708 4mg by mouth weekly (days 1, 8, 15) every 28 days. MLN9708
Objective Response Rate	8 percentage of patients Interval 1.5 to 35.0

SECONDARY outcome

Timeframe: 30 days after the last dose of study drug

To assess the safety and tolerability of MLN9708, the number of patients experiencing Adverse Events (AEs) greater than or equal to grade 3 will be recorded.

Outcome measures

Outcome measures
Measure	MLN9708 n=12 Participants MLN9708 4mg by mouth weekly (days 1, 8, 15) every 28 days. MLN9708
Number Patients That Experience Adverse Events, Grades 3-5 Anemia	1 participants
Number Patients That Experience Adverse Events, Grades 3-5 Thrombocytopenia	1 participants
Number Patients That Experience Adverse Events, Grades 3-5 Diarrhea	1 participants
Number Patients That Experience Adverse Events, Grades 3-5 Mucocitis	1 participants
Number Patients That Experience Adverse Events, Grades 3-5 Acute Kidney Injury	1 participants
Number Patients That Experience Adverse Events, Grades 3-5 Atrial Fibrilation	1 participants
Number Patients That Experience Adverse Events, Grades 3-5 Dyspnea	1 participants
Number Patients That Experience Adverse Events, Grades 3-5 Hypercalcemia	1 participants
Number Patients That Experience Adverse Events, Grades 3-5 Hyponatremia	1 participants
Number Patients That Experience Adverse Events, Grades 3-5 Hypotension	1 participants
Number Patients That Experience Adverse Events, Grades 3-5 Lymph Node Pain	1 participants
Number Patients That Experience Adverse Events, Grades 3-5 Rash	1 participants
Number Patients That Experience Adverse Events, Grades 3-5 Respiratory Failure	1 participants
Number Patients That Experience Adverse Events, Grades 3-5 Supraventricular Tachycardia	1 participants
Number Patients That Experience Adverse Events, Grades 3-5 Thromboembolic Event	1 participants

SECONDARY outcome

Timeframe: 24 months after initiation of study treatment

Population: 5 of the 12 patients withdrew prior to progression and therefore progression free survival was censored at their time of withdraw.

Progression Free Survival (PFS) is defined as the time from study start until disease progression or death.

Outcome measures

Outcome measures
Measure	MLN9708 n=12 Participants MLN9708 4mg by mouth weekly (days 1, 8, 15) every 28 days. MLN9708
Median Progression Free Survival Time	3.2 months Interval 1.6 to the upper limit was not reached

SECONDARY outcome

Timeframe: 24 months after initiation of study treatment

Population: Five patients died between start of treatment and database lock. Patients who were alive at the time of the database lock (March 31st, 2017) were administratively censored.

Overall Survival (OS) is defined as the time from study start until death.

Outcome measures

Outcome measures
Measure	MLN9708 n=12 Participants MLN9708 4mg by mouth weekly (days 1, 8, 15) every 28 days. MLN9708
Median Overall Survival Time	NA months Interval 8.1 to The median overall survival time at 24 months could not be estimated. The lower bound of the 95% confidence interval was 8.1 months.

SECONDARY outcome

Timeframe: 24 months after initiation of study treatment

Population: Although 12 patients were analyzable, only one patient responded to treatment and therefore only 1 patient is represented for the duration of response.

Time from documentation of tumor response to disease progression.

Outcome measures

Outcome measures
Measure	MLN9708 n=1 Participants MLN9708 4mg by mouth weekly (days 1, 8, 15) every 28 days. MLN9708
Duration of Response	12 months

Adverse Events

MLN9708

Serious events: 8 serious events

Other events: 10 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	MLN9708 n=12 participants at risk MLN9708 4mg by mouth weekly (days 1, 8, 15) every 28 days.
Renal and urinary disorders Acute kidney injury	8.3% 1/12 • Number of events 1
Blood and lymphatic system disorders Anemia	8.3% 1/12 • Number of events 1
Cardiac disorders Atrial fibrillation	8.3% 1/12 • Number of events 1
Gastrointestinal disorders Diarrhea	8.3% 1/12 • Number of events 1
Respiratory, thoracic and mediastinal disorders Dyspnea	8.3% 1/12 • Number of events 1
Metabolism and nutrition disorders Hypercalcemia	8.3% 1/12 • Number of events 1
Cardiac disorders Hypotension	8.3% 1/12 • Number of events 1
Investigations Platelet count decreased	8.3% 1/12 • Number of events 1
Investigations Rash maculo-papular	8.3% 1/12 • Number of events 1
Renal and urinary disorders Renal and urinary disorders - Other, specify	8.3% 1/12 • Number of events 1
Respiratory, thoracic and mediastinal disorders Respiratory failure	8.3% 1/12 • Number of events 1
Infections and infestations Sepsis	8.3% 1/12 • Number of events 1
Cardiac disorders Supraventricular tachycardia	8.3% 1/12 • Number of events 1
Vascular disorders Thromboembolic event	8.3% 1/12 • Number of events 2

Other adverse events

Other adverse events
Measure	MLN9708 n=12 participants at risk MLN9708 4mg by mouth weekly (days 1, 8, 15) every 28 days.
Gastrointestinal disorders Abdominal pain	8.3% 1/12 • Number of events 2
Investigations Alanine aminotransferase increased	8.3% 1/12 • Number of events 1
Metabolism and nutrition disorders Anorexia	8.3% 1/12 • Number of events 1
Musculoskeletal and connective tissue disorders Arthralgia	8.3% 1/12 • Number of events 1
Investigations Aspartate aminotransferase increased	16.7% 2/12 • Number of events 2
Musculoskeletal and connective tissue disorders Back pain	16.7% 2/12 • Number of events 2
General disorders Chills	8.3% 1/12 • Number of events 1
Gastrointestinal disorders Constipation	16.7% 2/12 • Number of events 2
Nervous system disorders Dysarthria	8.3% 1/12 • Number of events 1
Gastrointestinal disorders Dysgeusia	8.3% 1/12 • Number of events 1
General disorders Edema limbs	16.7% 2/12 • Number of events 2
General disorders Fatigue	16.7% 2/12 • Number of events 2
Metabolism and nutrition disorders Hyponatremia	8.3% 1/12 • Number of events 2
Endocrine disorders Hypothyroidism	8.3% 1/12 • Number of events 1
Blood and lymphatic system disorders Lymph node pain	8.3% 1/12 • Number of events 1
Gastrointestinal disorders Mucositis oral	8.3% 1/12 • Number of events 1
Gastrointestinal disorders Nausea	16.7% 2/12 • Number of events 2
Musculoskeletal and connective tissue disorders Pain in extremity	8.3% 1/12 • Number of events 1
Nervous system disorders Peripheral sensory neuropathy	25.0% 3/12 • Number of events 5
Skin and subcutaneous tissue disorders Pruritus	16.7% 2/12 • Number of events 2
Skin and subcutaneous tissue disorders Rash acneiform	8.3% 1/12 • Number of events 1
Infections and infestations Skin infection	8.3% 1/12 • Number of events 1
Skin and subcutaneous tissue disorders Skin ulceration	8.3% 1/12 • Number of events 1
Infections and infestations Upper respiratory infection	16.7% 2/12 • Number of events 3
Gastrointestinal disorders Vomiting	25.0% 3/12 • Number of events 3

Additional Information

Dr. Ryan Wilcox, M.D.

University of Michigan Comprehensive Cancer Center

Phone: 734-615-1482

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place