Trial Outcomes & Findings for Pembrolizumab, Ixazomib Citrate, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma (NCT NCT03506360)

Results Overview

Defined as a partial response or better noted as the objective status on two consecutive evaluations. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

13 participants

Primary outcome timeframe

Up to 9 months

Results posted on

2024-01-09

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (Ixazomib Citrate, Pembrolizumab, Dexamethasone) Patients receive ixazomib citrate PO on days 1, 8, 15, 29, 36, 43, 57, 64, and 71 and pembrolizumab IV over 30 minutes on days 1, 22, 43, 64. Patients also receive dexamethasone PO on days 1, 8, 15, 29, 36, 43, 57, 64, and 71. Cycles with dexamethasone repeat every 84 days for up to 1 year and cycles with ixazomib citrate and pembrolizumab repeat every 84 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	13
Overall Study COMPLETED	13
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pembrolizumab, Ixazomib Citrate, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Ixazomib Citrate, Pembrolizumab, and Dexamethasone) n=13 Participants Patients receive ixazomib citrate PO on days 1, 8, 15, 29, 36, 43, 57, 64, and 71 and pembrolizumab IV over 30 minutes on days 1, 22, 43, 64. Patients also receive dexamethasone PO on days 1, 8, 15, 29, 36, 43, 57, 64, and 71. Cycles with dexamethasone repeat every 84 days for up to 1 year and cycles with ixazomib citrate and pembrolizumab repeat every 84 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Age, Continuous	67 years n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 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	13 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

PRIMARY outcome

Timeframe: Up to 9 months

Defined as a partial response or better noted as the objective status on two consecutive evaluations. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

Outcome measures

Outcome measures
Measure	Treatment (Ixazomib Citrate, Pembrolizumab, and Dexamethasone) n=13 Participants Patients receive ixazomib citrate PO on days 1, 8, 15, 29, 36, 43, 57, 64, and 71 and pembrolizumab IV over 30 minutes on days 1, 22, 43, 64. Patients also receive dexamethasone PO on days 1, 8, 15, 29, 36, 43, 57, 64, and 71. Cycles with dexamethasone repeat every 84 days for up to 1 year and cycles with ixazomib citrate and pembrolizumab repeat every 84 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Overall Response Percentage	0.077 percentage of responders Interval 0.004 to 0.322

SECONDARY outcome

Timeframe: Up to 9 months

Will be estimated by the number of patients who achieve a VGPR, complete response (CR), or stringent complete response (sCR) at any time divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success rate will be calculated.

Outcome measures

Outcome measures
Measure	Treatment (Ixazomib Citrate, Pembrolizumab, and Dexamethasone) n=13 Participants Patients receive ixazomib citrate PO on days 1, 8, 15, 29, 36, 43, 57, 64, and 71 and pembrolizumab IV over 30 minutes on days 1, 22, 43, 64. Patients also receive dexamethasone PO on days 1, 8, 15, 29, 36, 43, 57, 64, and 71. Cycles with dexamethasone repeat every 84 days for up to 1 year and cycles with ixazomib citrate and pembrolizumab repeat every 84 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
>= Very Good Partial Response (VGPR) Response Percentage With Pembrolizumab Added to Ixazomib Citrate and Dexamethasone	0 percentage of responders No events occurred, intervals are incalculable

SECONDARY outcome

Timeframe: Up to 2 years

Will be estimated by the number of patients who achieve a CR or sCR at any time divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success rate will be calculated.

Outcome measures

Outcome measures
Measure	Treatment (Ixazomib Citrate, Pembrolizumab, and Dexamethasone) n=13 Participants Patients receive ixazomib citrate PO on days 1, 8, 15, 29, 36, 43, 57, 64, and 71 and pembrolizumab IV over 30 minutes on days 1, 22, 43, 64. Patients also receive dexamethasone PO on days 1, 8, 15, 29, 36, 43, 57, 64, and 71. Cycles with dexamethasone repeat every 84 days for up to 1 year and cycles with ixazomib citrate and pembrolizumab repeat every 84 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Complete Response Percentage With Pembrolizumab Added to Ixazomib Citrate and Dexamethasone	0 percentage of responders No events occurred, intervals incalculable

SECONDARY outcome

Timeframe: Up to 2 years

The distribution of survival time will be estimated using the method of Kaplan-Meier.

Outcome measures

Outcome measures
Measure	Treatment (Ixazomib Citrate, Pembrolizumab, and Dexamethasone) n=13 Participants Patients receive ixazomib citrate PO on days 1, 8, 15, 29, 36, 43, 57, 64, and 71 and pembrolizumab IV over 30 minutes on days 1, 22, 43, 64. Patients also receive dexamethasone PO on days 1, 8, 15, 29, 36, 43, 57, 64, and 71. Cycles with dexamethasone repeat every 84 days for up to 1 year and cycles with ixazomib citrate and pembrolizumab repeat every 84 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Survival Time	9 Months Interval 3.0 to No enough events occurred to obtain an upper limit.

SECONDARY outcome

Timeframe: Up to 2 years

The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.

Outcome measures

Outcome measures
Measure	Treatment (Ixazomib Citrate, Pembrolizumab, and Dexamethasone) n=13 Participants Patients receive ixazomib citrate PO on days 1, 8, 15, 29, 36, 43, 57, 64, and 71 and pembrolizumab IV over 30 minutes on days 1, 22, 43, 64. Patients also receive dexamethasone PO on days 1, 8, 15, 29, 36, 43, 57, 64, and 71. Cycles with dexamethasone repeat every 84 days for up to 1 year and cycles with ixazomib citrate and pembrolizumab repeat every 84 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Progression-free Survival	1.6 Months Interval 0.7 to 2.8

SECONDARY outcome

Timeframe: Up to 9 months

Graded according National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.

Outcome measures

Outcome measures
Measure	Treatment (Ixazomib Citrate, Pembrolizumab, and Dexamethasone) n=13 Participants Patients receive ixazomib citrate PO on days 1, 8, 15, 29, 36, 43, 57, 64, and 71 and pembrolizumab IV over 30 minutes on days 1, 22, 43, 64. Patients also receive dexamethasone PO on days 1, 8, 15, 29, 36, 43, 57, 64, and 71. Cycles with dexamethasone repeat every 84 days for up to 1 year and cycles with ixazomib citrate and pembrolizumab repeat every 84 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Incidence of Adverse Events	13 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

Each measure will be summarized descriptively by median, minimum (min), maximum (max) and interquartile range.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Cycle 3 (84 days - each Cycle is 28 days)

Will be summarized descriptively by median, min, max, and interquartile range at each time point. Patterns over time will be summarized by absolute difference or relative change. Changes across time will be assessed using paired analyses, including Wilcoxon signed rank tests. Jitplots will be used to visually examine differences between groups for continuous factors.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to Cycle 3 (84 days - each Cycle is 28 days)

Will be summarized descriptively by median, min, max, and interquartile range at each time point. Patterns over time will be summarized by absolute difference or relative change. Changes across time will be assessed using paired analyses, including Wilcoxon signed rank tests. Jitplots will be used to visually examine differences between groups for continuous factors.

Outcome measures

Outcome data not reported

Adverse Events

Treatment (Ixazomib Citrate, Pembrolizumab, and Dexamethasone)

Serious events: 1 serious events

Other events: 12 other events

Deaths: 6 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Ixazomib Citrate, Pembrolizumab, and Dexamethasone) n=13 participants at risk Patients receive ixazomib citrate PO on days 1, 8, 15, 29, 36, 43, 57, 64, and 71 and pembrolizumab IV over 30 minutes on days 1, 22, 43, 64. Patients also receive dexamethasone PO on days 1, 8, 15, 29, 36, 43, 57, 64, and 71. Cycles with dexamethasone repeat every 84 days for up to 1 year and cycles with ixazomib citrate and pembrolizumab repeat every 84 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Gastrointestinal disorders Gastrointestinal disorders - Oth spec	7.7% 1/13 • Number of events 1 • 2 years

Other adverse events

Other adverse events
Measure	Treatment (Ixazomib Citrate, Pembrolizumab, and Dexamethasone) n=13 participants at risk Patients receive ixazomib citrate PO on days 1, 8, 15, 29, 36, 43, 57, 64, and 71 and pembrolizumab IV over 30 minutes on days 1, 22, 43, 64. Patients also receive dexamethasone PO on days 1, 8, 15, 29, 36, 43, 57, 64, and 71. Cycles with dexamethasone repeat every 84 days for up to 1 year and cycles with ixazomib citrate and pembrolizumab repeat every 84 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	46.2% 6/13 • Number of events 9 • 2 years
Gastrointestinal disorders Constipation	46.2% 6/13 • Number of events 19 • 2 years
Gastrointestinal disorders Diarrhea	23.1% 3/13 • Number of events 10 • 2 years
Gastrointestinal disorders Nausea	38.5% 5/13 • Number of events 10 • 2 years
Gastrointestinal disorders Vomiting	7.7% 1/13 • Number of events 1 • 2 years
General disorders Fatigue	92.3% 12/13 • Number of events 40 • 2 years
Investigations Creatinine increased	53.8% 7/13 • Number of events 22 • 2 years
Investigations Lymphocyte count decreased	46.2% 6/13 • Number of events 19 • 2 years
Investigations Lymphocyte count increased	15.4% 2/13 • Number of events 2 • 2 years
Investigations Neutrophil count decreased	23.1% 3/13 • Number of events 4 • 2 years
Investigations Platelet count decreased	84.6% 11/13 • Number of events 32 • 2 years
Investigations White blood cell decreased	7.7% 1/13 • Number of events 1 • 2 years
Metabolism and nutrition disorders Hyperglycemia	7.7% 1/13 • Number of events 6 • 2 years
Skin and subcutaneous tissue disorders Rash maculo-papular	15.4% 2/13 • Number of events 3 • 2 years

Additional Information

Yi Lin

Mayo Clinic

Phone: 5072845096

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place