Trial Outcomes & Findings for Sonidegib and Lenalidomide After Stem Cell Transplant in Treating Patients With Multiple Myeloma (NCT NCT02086552)

NCT ID: NCT02086552

Last Updated: 2021-12-03

Results Overview

A comfirmed Complete Response (CR) is defined as a CR noted as the objective status on 2 consecutive evaluations. To be categorized as a CR, patients must exhibit the following:\> * Negative immunofixation of serum and urine c, and\> * Disappearance of any soft tissue plasmacytoma, and\> * \<5% plasma cells in Bone Marrow, and\> * If the only measurable disease is the serum free light chain (FLC), a normal FLC ratio.\> We are reporting the proportion of patients achieving a CR or higher divided by the total number of evaluable patients.\> Exact binomial 95% confidence intervals for the true success proportion will be calculated.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

28 participants

Primary outcome timeframe

Up to 2 years

Results posted on

2021-12-03

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (Sonidegib, Lenalidomide) Patients receive 400 mg sonidegib PO QD on days 1-28 and 10 mg lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	28
Overall Study COMPLETED	27
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (Sonidegib, Lenalidomide) Patients receive 400 mg sonidegib PO QD on days 1-28 and 10 mg lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Sonidegib and Lenalidomide After Stem Cell Transplant in Treating Patients With Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Sonidegib, Lenalidomide) n=28 Participants Patients receive 400 mg sonidegib PO QD on days 1-28 and 10 mg lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.
Age, Continuous	59.5 years n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	27 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	28 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 2 years

Population: Of the 28 patients registered, one cancelled prior to treatment and 1 was ineligible due to protocol violation. Therefore 26 patients were used in this analysis.

Outcome measures

Outcome measures
Measure	Treatment (Sonidegib, Lenalidomide) n=26 Participants Patients receive 400 mg sonidegib PO QD on days 1-28 and 10 mg lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.
Complete Response, Assessed Using the International Myeloma Working Group (IMWG) Uniform Response Criteria	0.48 proportion of patients Interval 0.27 to 0.69

SECONDARY outcome

Timeframe: Time from SCT to death due to any cause, assessed up to 3 years

Population: All patients that began protocol treatment and were eligible were included in this endpoint.

Overall Survival (OS) is defined as the time from Stem Cell Transplant (SCT) to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.

Outcome measures

Outcome measures
Measure	Treatment (Sonidegib, Lenalidomide) n=26 Participants Patients receive 400 mg sonidegib PO QD on days 1-28 and 10 mg lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.
Overall Survival	NA years Interval 4.3 to Too few events have occurred to estimate the median and upper 95% confidence interval.

SECONDARY outcome

Timeframe: Time from SCT to progression or death due to any cause, assessed at 1 year

Population: All patients that were treated and evaluable were included in this endpoint.

The progression-free survival time is defined as the time from SCT to progression or death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier. Here, we are reporting the proportion of patients that have not had a PFS event one year after SCT.

Outcome measures

Outcome measures
Measure	Treatment (Sonidegib, Lenalidomide) n=26 Participants Patients receive 400 mg sonidegib PO QD on days 1-28 and 10 mg lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.
Progression-free Survival (1 Year Survival Rate)	0.88 proportion of participants Interval 0.76 to 100.0

SECONDARY outcome

Timeframe: Time from SCT to progression or death due to any cause, assessed at 2 years

Population: All patients that began protocol treatment and were evaluable were included in this endpoint.

Outcome measures

Outcome measures
Measure	Treatment (Sonidegib, Lenalidomide) n=26 Participants Patients receive 400 mg sonidegib PO QD on days 1-28 and 10 mg lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.
Progression-free Survival	0.76 proportion of participants Interval 0.61 to 0.94

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 years

Exact binomial 95% confidence intervals for the true MRD negative rate will be calculated.

Outcome measures

Outcome data not reported

Adverse Events

Treatment (Sonidegib, Lenalidomide)

Serious events: 5 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Sonidegib, Lenalidomide) n=27 participants at risk Patients receive 400 mg sonidegib PO QD on days 1-28 and 10 mg lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Febrile neutropenia	3.7% 1/27 • Number of events 1 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Gastrointestinal disorders Nausea	3.7% 1/27 • Number of events 1 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Infections and infestations Lung infection	3.7% 1/27 • Number of events 1 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Nervous system disorders Syncope	3.7% 1/27 • Number of events 1 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Renal and urinary disorders Acute kidney injury	3.7% 1/27 • Number of events 1 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Renal and urinary disorders Hematuria	3.7% 1/27 • Number of events 1 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Vascular disorders Thromboembolic event	3.7% 1/27 • Number of events 1 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.

Other adverse events

Other adverse events
Measure	Treatment (Sonidegib, Lenalidomide) n=27 participants at risk Patients receive 400 mg sonidegib PO QD on days 1-28 and 10 mg lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 18 courses in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	11.1% 3/27 • Number of events 9 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Blood and lymphatic system disorders Febrile neutropenia	3.7% 1/27 • Number of events 1 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Ear and labyrinth disorders Tinnitus	7.4% 2/27 • Number of events 18 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Eye disorders Blurred vision	3.7% 1/27 • Number of events 3 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Gastrointestinal disorders Abdominal pain	3.7% 1/27 • Number of events 1 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Gastrointestinal disorders Constipation	37.0% 10/27 • Number of events 46 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Gastrointestinal disorders Diarrhea	74.1% 20/27 • Number of events 147 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Gastrointestinal disorders Gastritis	3.7% 1/27 • Number of events 2 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Gastrointestinal disorders Vomiting	37.0% 10/27 • Number of events 13 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
General disorders Fatigue	92.6% 25/27 • Number of events 248 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Infections and infestations Bladder infection	3.7% 1/27 • Number of events 1 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Infections and infestations Corneal infection	3.7% 1/27 • Number of events 1 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Infections and infestations Infections and infestations - Other, specify	7.4% 2/27 • Number of events 5 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Infections and infestations Sinusitis	3.7% 1/27 • Number of events 1 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Investigations Alanine aminotransferase increased	3.7% 1/27 • Number of events 1 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Investigations Alkaline phosphatase increased	7.4% 2/27 • Number of events 2 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Investigations CPK increased	3.7% 1/27 • Number of events 1 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Investigations Lymphocyte count decreased	18.5% 5/27 • Number of events 23 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Investigations Neutrophil count decreased	85.2% 23/27 • Number of events 133 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Investigations Platelet count decreased	66.7% 18/27 • Number of events 85 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Investigations Weight loss	18.5% 5/27 • Number of events 12 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Investigations White blood cell decreased	70.4% 19/27 • Number of events 107 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Metabolism and nutrition disorders Anorexia	11.1% 3/27 • Number of events 4 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Metabolism and nutrition disorders Dehydration	3.7% 1/27 • Number of events 1 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Musculoskeletal and connective tissue disorders Arthralgia	7.4% 2/27 • Number of events 19 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	14.8% 4/27 • Number of events 16 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Musculoskeletal and connective tissue disorders Myalgia	70.4% 19/27 • Number of events 146 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Nervous system disorders Dysgeusia	44.4% 12/27 • Number of events 44 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Nervous system disorders Headache	3.7% 1/27 • Number of events 3 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Nervous system disorders Peripheral sensory neuropathy	74.1% 20/27 • Number of events 187 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Respiratory, thoracic and mediastinal disorders Cough	3.7% 1/27 • Number of events 1 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Skin and subcutaneous tissue disorders Alopecia	18.5% 5/27 • Number of events 11 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Skin and subcutaneous tissue disorders Dry skin	3.7% 1/27 • Number of events 2 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Skin and subcutaneous tissue disorders Rash maculo-papular	51.9% 14/27 • Number of events 29 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	11.1% 3/27 • Number of events 3 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Vascular disorders Hot flashes	7.4% 2/27 • Number of events 7 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Vascular disorders Hypertension	3.7% 1/27 • Number of events 1 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.
Vascular disorders Thromboembolic event	7.4% 2/27 • Number of events 10 • Adverse events were collected at the end of each 28-day cycle, for up to 18 cycles. Adverse events were collected systematically at the end of each 28-day cycle, for up to 18 cycles.

Additional Information

Francis K Buadi, MD

Mayo Clinic

Phone: 507/284-2511

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place