Trial Outcomes & Findings for Phase I Trial of Everolimus, Pomalidomide and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma (NCT NCT01889420)

Last Updated: 2015-07-31

Results Overview

The Maximum Tolerated Dose (MTD) will be determined by first identifying the dose level at which \>= 30% of patients experience a Dose Limiting Toxicity (DLT) according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, over a 28 day cycle. DLT will be defined based on the rate of drug-related grade 3-5, non-hematological adverse events experienced within the first 4 weeks (1 cycle) for each combined dosage scheme. The MTD will be defined as one dosage level below which DLT was observed in \>= 30% of patients.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

1 participants

Primary outcome timeframe

2 years

Results posted on

2015-07-31

Participant Flow

Participant milestones

Participant milestones
Measure	Combination Therapy Pomalidomide: 1 tablet orally, daily for 21 days of a 28 day cycle (dose per cohort) Everolimus: 1 tablet orally for 21 days of a 28 day cycle (dose as per cohort) Dexamethasone 40 mg (20 mg \>75yrs) orally, days 1, 8,15, 22 of a 28 day cycle Combination therapy: Following determination of the maximum tolerated dosages in the phase I portion of this study, all patients enrolled in the extension portion will receive the predetermined dosage combination of pomalidomide, everolimus and dexamethasone. Cycles will span 28 days. Dosage schedules will be: 1. Everolimus daily for 28 days of a 28 day cycle; 2. Pomalidomide daily for 21 days of a 28 day cycle 3. Dexamethasone once weekly (on days 1,8,15,22) of a 28 day cycle.
Overall Study STARTED	1
Overall Study COMPLETED	1
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase I Trial of Everolimus, Pomalidomide and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Combination Therapy n=1 Participants Pomalidomide: 1 tablet orally, daily for 21 days of a 28 day cycle (dose per cohort) Everolimus: 1 tablet orally for 21 days of a 28 day cycle (dose as per cohort) Dexamethasone 40 mg (20 mg \>75yrs) orally, days 1, 8,15, 22 of a 28 day cycle Combination therapy: Following determination of the maximum tolerated dosages in the phase I portion of this study, all patients enrolled in the extension portion will receive the predetermined dosage combination of pomalidomide, everolimus and dexamethasone. Cycles will span 28 days. Dosage schedules will be: 1. Everolimus daily for 28 days of a 28 day cycle; 2. Pomalidomide daily for 21 days of a 28 day cycle 3. Dexamethasone once weekly (on days 1,8,15,22) of a 28 day cycle.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Region of Enrollment United States	1 participants n=5 Participants

PRIMARY outcome

Timeframe: 2 years

Population: There was only one patient enrolled. The MTD could not be calculated based on one patient.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 years

The toxicity profile will be described by specific adverse event rates among patients experiencing \> grade 3 hematologic events (lasting \>7 days) or grades 3-5 non-hematologic adverse events, according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, over a 28 day cycle. Specific events will be described as the numbers of patients experiencing them within each treatment cohort.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 3.5 years

Population: There was only one patient enrolled. Anti-tumor effect cannot be reported accurately based on results from one patient.

Anti-tumor effect will be assessed based on serum protein electrophoresis (SPEP) of the monoclonal protein (M-protein) and plasma concentrations of K/L free light chains (FLC) after each 28-day cycle. Descriptive statistics will be used for this measurement. Complete response (CR): disappearance of any M-protein and FLC as measured by SPEP and/or FLC. Pre-existing plasmacytomas must have completely resolved. Partial response (PR): \>50% reduction in M-protein and \>50% reduction in the difference between involved and uninvolved FLC. Any plasmacytoma must have decreased in size by \>50%. Stable disease: not meeting criteria for CR, PR, or progressive disease (PD). PD: \>25% increase from baseline in serum or urine M-protein (serum M-protein must increase by \> 0.5 gm/dl; urine M-protein must increase by \>200 mg /24 hr); or development of new plasmacytomas or new lytic bone lesions; or a measurable increase in the size of these lesions; or hypercalcemia (\>11.5 mg/dl) attributed to MM.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 3 years

Population: There was only one patient enrolled. Response rates cannot be accurately reported based on one patient.

ORR is the percentage of patients with a \> Partial Response (PR). Response is assessed based on serum protein electrophoresis (SPEP) of the monoclonal protein (M-protein) and plasma concentrations of K/L free light chains (FLC) after each 28-day cycle. Complete response (CR): disappearance of any M-protein and FLC as measured by SPEP and/or FLC. Pre-existing plasmacytomas must have completely resolved. PR: \>50% reduction in M-protein and \>50% reduction in the difference between involved and uninvolved FLC. Any plasmacytoma must have decreased in size by \>50%. Stable disease: not meeting criteria for CR, PR, or progressive disease (PD). PD: \>25% increase from baseline in serum or urine M-protein (serum M-protein must increase by \> 0.5 gm/dl; urine M-protein must increase by \>200 mg /24 hr); or development of new plasmacytomas or new lytic bone lesions; or a measurable increase in the size of these lesions; or hypercalcemia (\>11.5 mg/dl) attributed to MM.

Outcome measures

Outcome data not reported

Adverse Events

Combination Therapy

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Combination Therapy n=1 participants at risk Pomalidomide: 1 tablet orally, daily for 21 days of a 28 day cycle (dose per cohort) Everolimus: 1 tablet orally for 21 days of a 28 day cycle (dose as per cohort) Dexamethasone 40 mg (20 mg \>75yrs) orally, days 1, 8,15, 22 of a 28 day cycle Combination therapy: Following determination of the maximum tolerated dosages in the phase I portion of this study, all patients enrolled in the extension portion will receive the predetermined dosage combination of pomalidomide, everolimus and dexamethasone. Cycles will span 28 days. Dosage schedules will be: 1. Everolimus daily for 28 days of a 28 day cycle; 2. Pomalidomide daily for 21 days of a 28 day cycle 3. Dexamethasone once weekly (on days 1,8,15,22) of a 28 day cycle.
Skin and subcutaneous tissue disorders Alopecia (Hair loss)	100.0% 1/1 • Number of events 1
Blood and lymphatic system disorders Anemia (hemoglobin levels decreased)	100.0% 1/1 • Number of events 1
General disorders Fatigue	100.0% 1/1 • Number of events 6
Nervous system disorders Headache	100.0% 1/1 • Number of events 1
Investigations Hypernatremia (high blood sodium)	100.0% 1/1 • Number of events 1
Investigations Hypoalbuminemia (low blood albumin)	100.0% 1/1 • Number of events 1
Investigations Hypokalemia (low blood potassium)	100.0% 1/1 • Number of events 1
Infections and infestations Infections and infestations - Other	100.0% 1/1 • Number of events 1
Gastrointestinal disorders Mucositis oral	100.0% 1/1 • Number of events 1
Gastrointestinal disorders Nausea	100.0% 1/1 • Number of events 1
Blood and lymphatic system disorders Neutrophil count decreased	100.0% 1/1 • Number of events 1
Nervous system disorders Paresthesia (tingling, burning sensation)	100.0% 1/1 • Number of events 1
Skin and subcutaneous tissue disorders Rash acneiform	100.0% 1/1 • Number of events 3
Gastrointestinal disorders Vomiting	100.0% 1/1 • Number of events 1
Blood and lymphatic system disorders White blood cell count decreased	100.0% 1/1 • Number of events 1

Additional Information

Dulcinea Quintana, MD

University of New Mexico

Phone: 505-272-4661

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place