Trial Outcomes & Findings for Carfilzomib, Rituximab and Dexamethasone in Waldenstrom's Macroglobulinemia (NCT NCT01470196)

Last Updated: 2018-11-20

Results Overview

Overall Response Rate= Minor response (\>25%-50% reduction in serum IgM from baseline + Partial Response (\>50-90% reduction in serum IgM from baseline) + Very Good Partial Response (\>90% reduction in serum IgM from baseline) + Complete Response (resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, resolution of any adenopathy or splenomegaly).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

31 participants

Primary outcome timeframe

4 years

Results posted on

2018-11-20

Participant Flow

Participant milestones

Participant milestones
Measure	Carfilzomib, Dexamethasone, and Rituximab Carfilzomib, dexamethasone, rituximab Dexamethasone: 20 mg IV on Days 1, 2, 8, 9, of 21 day cycle for cycles 1-6 20 mg IV on Days 1, 2 of 21 day cycles q 2 months for cycles 1-8 Carfilzomib: 20 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycle 1 36 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycles 2-6 36 mg/m2 IV on Days 1, 2 of 21 day cycles q 2 months for Cycles 1-8 Rituximab: 375 mg/m2 IV on Days 2, 9 of 21 day cycles for Cycles 1-6 375 mg/m2 IV on Day 2 of 21 day cycles q 2 months for Cycles 1-8
Overall Study STARTED	31
Overall Study COMPLETED	31
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Carfilzomib, Rituximab and Dexamethasone in Waldenstrom's Macroglobulinemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment Arm n=31 Participants Carfilzomib, dexamethasone, rituximab Dexamethasone: 20 mg IV on Days 1, 2, 8, 9, of 21 day cycle for cycles 1-6 20 mg IV on Days 1, 2 of 21 day cycles q 2 months for cycles 1-8 Carfilzomib: 20 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycle 1 36 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycles 2-6 36 mg/m2 IV on Days 1, 2 of 21 day cycles q 2 months for Cycles 1-8 Rituximab: 375 mg/m2 IV on Days 2, 9 of 21 day cycles for Cycles 1-6 375 mg/m2 IV on Day 2 of 21 day cycles q 2 months for Cycles 1-8
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	21 Participants n=5 Participants
Age, Categorical >=65 years	10 Participants n=5 Participants
Age, Continuous	61 years n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants
Region of Enrollment United States	31 Participants n=5 Participants

PRIMARY outcome

Timeframe: 4 years

Outcome measures

Outcome measures
Measure	Treatment Arm n=31 Participants Carfilzomib, dexamethasone, rituximab Dexamethasone: 20 mg IV on Days 1, 2, 8, 9, of 21 day cycle for cycles 1-6 20 mg IV on Days 1, 2 of 21 day cycles q 2 months for cycles 1-8 Carfilzomib: 20 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycle 1 36 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycles 2-6 36 mg/m2 IV on Days 1, 2 of 21 day cycles q 2 months for Cycles 1-8 Rituximab: 375 mg/m2 IV on Days 2, 9 of 21 day cycles for Cycles 1-6 375 mg/m2 IV on Day 2 of 21 day cycles q 2 months for Cycles 1-8
Overall Response Rate	25 Participants

PRIMARY outcome

Timeframe: 3 years

Number and percentage of participants who experienced neuropathy attributable to CaRD therapy

Outcome measures

Outcome measures
Measure	Treatment Arm n=31 Participants Carfilzomib, dexamethasone, rituximab Dexamethasone: 20 mg IV on Days 1, 2, 8, 9, of 21 day cycle for cycles 1-6 20 mg IV on Days 1, 2 of 21 day cycles q 2 months for cycles 1-8 Carfilzomib: 20 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycle 1 36 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycles 2-6 36 mg/m2 IV on Days 1, 2 of 21 day cycles q 2 months for Cycles 1-8 Rituximab: 375 mg/m2 IV on Days 2, 9 of 21 day cycles for Cycles 1-6 375 mg/m2 IV on Day 2 of 21 day cycles q 2 months for Cycles 1-8
Neuropathy Incidence Rate	6 Participants

PRIMARY outcome

Timeframe: 4 years

Progression-free survival is the defined as the time from study entry to disease progression (PD) or death. Patients without PD are censored at the date of last disease evaluation. PD is defined as a greater than 25% increase in serum IgM and 500mg/dL absolute increase from the lowest attained response value as determined by serum electrophoresis, confirmed by at least one other investigation, or progression of clinically significant disease related symptom(s).

Outcome measures

Outcome measures
Measure	Treatment Arm n=31 Participants Carfilzomib, dexamethasone, rituximab Dexamethasone: 20 mg IV on Days 1, 2, 8, 9, of 21 day cycle for cycles 1-6 20 mg IV on Days 1, 2 of 21 day cycles q 2 months for cycles 1-8 Carfilzomib: 20 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycle 1 36 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycles 2-6 36 mg/m2 IV on Days 1, 2 of 21 day cycles q 2 months for Cycles 1-8 Rituximab: 375 mg/m2 IV on Days 2, 9 of 21 day cycles for Cycles 1-6 375 mg/m2 IV on Day 2 of 21 day cycles q 2 months for Cycles 1-8
Time to Progression	58 months Interval 9.0 to 65.0

PRIMARY outcome

Timeframe: 4 years

Major Response Rate= Partial Response (\>50-90% reduction in serum IgM from baseline) + Very Good Partial Response (\>90% reduction in serum IgM from baseline) + Complete Response (resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, resolution of any adenopathy or splenomegaly).

Outcome measures

Outcome measures
Measure	Treatment Arm n=31 Participants Carfilzomib, dexamethasone, rituximab Dexamethasone: 20 mg IV on Days 1, 2, 8, 9, of 21 day cycle for cycles 1-6 20 mg IV on Days 1, 2 of 21 day cycles q 2 months for cycles 1-8 Carfilzomib: 20 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycle 1 36 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycles 2-6 36 mg/m2 IV on Days 1, 2 of 21 day cycles q 2 months for Cycles 1-8 Rituximab: 375 mg/m2 IV on Days 2, 9 of 21 day cycles for Cycles 1-6 375 mg/m2 IV on Day 2 of 21 day cycles q 2 months for Cycles 1-8
Major Response Rate	22 Participants

PRIMARY outcome

Timeframe: 4 years

This is the rate of VGPR and CR in patients on CaRD therapy. Very good partial responses are \>90% reduction in serum IgM from baseline. Complete response is defined as having resolution of all symptoms, normalization of serum IgM levels with complete disappearance of IgM paraprotein by immunofixation, and resolution of any adenopathy or splenomegaly.

Outcome measures

Outcome measures
Measure	Treatment Arm n=31 Participants Carfilzomib, dexamethasone, rituximab Dexamethasone: 20 mg IV on Days 1, 2, 8, 9, of 21 day cycle for cycles 1-6 20 mg IV on Days 1, 2 of 21 day cycles q 2 months for cycles 1-8 Carfilzomib: 20 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycle 1 36 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycles 2-6 36 mg/m2 IV on Days 1, 2 of 21 day cycles q 2 months for Cycles 1-8 Rituximab: 375 mg/m2 IV on Days 2, 9 of 21 day cycles for Cycles 1-6 375 mg/m2 IV on Day 2 of 21 day cycles q 2 months for Cycles 1-8
Very Good Partial Response and Complete Response Rate	12 Participants

Adverse Events

Treatment Arm

Serious events: 5 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment Arm n=31 participants at risk Carfilzomib, dexamethasone, rituximab Dexamethasone: 20 mg IV on Days 1, 2, 8, 9, of 21 day cycle for cycles 1-6 20 mg IV on Days 1, 2 of 21 day cycles q 2 months for cycles 1-8 Carfilzomib: 20 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycle 1 36 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycles 2-6 36 mg/m2 IV on Days 1, 2 of 21 day cycles q 2 months for Cycles 1-8 Rituximab: 375 mg/m2 IV on Days 2, 9 of 21 day cycles for Cycles 1-6 375 mg/m2 IV on Day 2 of 21 day cycles q 2 months for Cycles 1-8
Cardiac disorders Atypical chest pain	3.2% 1/31 • Number of events 1 • Adverse events were assessed at every cycle visit (every 3 weeks during induction, and every 2 months during maintenance) and up to 30 days post end of treatment, up to 3 years.
Infections and infestations Pneumonia	3.2% 1/31 • Number of events 1 • Adverse events were assessed at every cycle visit (every 3 weeks during induction, and every 2 months during maintenance) and up to 30 days post end of treatment, up to 3 years.
Cardiac disorders Cardiomyopathy	3.2% 1/31 • Number of events 1 • Adverse events were assessed at every cycle visit (every 3 weeks during induction, and every 2 months during maintenance) and up to 30 days post end of treatment, up to 3 years.
Investigations Grade 4 Neutrophil count decreased	3.2% 1/31 • Number of events 1 • Adverse events were assessed at every cycle visit (every 3 weeks during induction, and every 2 months during maintenance) and up to 30 days post end of treatment, up to 3 years.
Injury, poisoning and procedural complications Postoperative thoracic procedure complication	3.2% 1/31 • Number of events 1 • Adverse events were assessed at every cycle visit (every 3 weeks during induction, and every 2 months during maintenance) and up to 30 days post end of treatment, up to 3 years.

Other adverse events

Other adverse events
Measure	Treatment Arm n=31 participants at risk Carfilzomib, dexamethasone, rituximab Dexamethasone: 20 mg IV on Days 1, 2, 8, 9, of 21 day cycle for cycles 1-6 20 mg IV on Days 1, 2 of 21 day cycles q 2 months for cycles 1-8 Carfilzomib: 20 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycle 1 36 mg/m2 IV on Days 1, 2, 8, 9 of 21 day cycles for Cycles 2-6 36 mg/m2 IV on Days 1, 2 of 21 day cycles q 2 months for Cycles 1-8 Rituximab: 375 mg/m2 IV on Days 2, 9 of 21 day cycles for Cycles 1-6 375 mg/m2 IV on Day 2 of 21 day cycles q 2 months for Cycles 1-8
Investigations Lipase increased	54.8% 17/31 • Adverse events were assessed at every cycle visit (every 3 weeks during induction, and every 2 months during maintenance) and up to 30 days post end of treatment, up to 3 years.
Investigations Serum amylase increased	25.8% 8/31 • Adverse events were assessed at every cycle visit (every 3 weeks during induction, and every 2 months during maintenance) and up to 30 days post end of treatment, up to 3 years.
Investigations Blood bilirubin increased	25.8% 8/31 • Adverse events were assessed at every cycle visit (every 3 weeks during induction, and every 2 months during maintenance) and up to 30 days post end of treatment, up to 3 years.
Metabolism and nutrition disorders Hyperglycemia	100.0% 31/31 • Adverse events were assessed at every cycle visit (every 3 weeks during induction, and every 2 months during maintenance) and up to 30 days post end of treatment, up to 3 years.
Nervous system disorders Peripheral Sensory Neuropathy	19.4% 6/31 • Adverse events were assessed at every cycle visit (every 3 weeks during induction, and every 2 months during maintenance) and up to 30 days post end of treatment, up to 3 years.
General disorders Infusion related reaction	25.8% 8/31 • Adverse events were assessed at every cycle visit (every 3 weeks during induction, and every 2 months during maintenance) and up to 30 days post end of treatment, up to 3 years.
Investigations Neutrophil count decreased	35.5% 11/31 • Adverse events were assessed at every cycle visit (every 3 weeks during induction, and every 2 months during maintenance) and up to 30 days post end of treatment, up to 3 years.
Infections and infestations Skin infection	29.0% 9/31 • Adverse events were assessed at every cycle visit (every 3 weeks during induction, and every 2 months during maintenance) and up to 30 days post end of treatment, up to 3 years.
Gastrointestinal disorders Oral mucositis	6.5% 2/31 • Adverse events were assessed at every cycle visit (every 3 weeks during induction, and every 2 months during maintenance) and up to 30 days post end of treatment, up to 3 years.
Musculoskeletal and connective tissue disorders Arthralgia	9.7% 3/31 • Adverse events were assessed at every cycle visit (every 3 weeks during induction, and every 2 months during maintenance) and up to 30 days post end of treatment, up to 3 years.
Gastrointestinal disorders GI cramping	3.2% 1/31 • Adverse events were assessed at every cycle visit (every 3 weeks during induction, and every 2 months during maintenance) and up to 30 days post end of treatment, up to 3 years.
General disorders Fatigue	6.5% 2/31 • Adverse events were assessed at every cycle visit (every 3 weeks during induction, and every 2 months during maintenance) and up to 30 days post end of treatment, up to 3 years.
Investigations Creatinine increased	9.7% 3/31 • Adverse events were assessed at every cycle visit (every 3 weeks during induction, and every 2 months during maintenance) and up to 30 days post end of treatment, up to 3 years.
Metabolism and nutrition disorders Hyperkalemia	3.2% 1/31 • Adverse events were assessed at every cycle visit (every 3 weeks during induction, and every 2 months during maintenance) and up to 30 days post end of treatment, up to 3 years.
Metabolism and nutrition disorders Hypokalemia	3.2% 1/31 • Adverse events were assessed at every cycle visit (every 3 weeks during induction, and every 2 months during maintenance) and up to 30 days post end of treatment, up to 3 years.
Investigations Platelet count decreased	3.2% 1/31 • Adverse events were assessed at every cycle visit (every 3 weeks during induction, and every 2 months during maintenance) and up to 30 days post end of treatment, up to 3 years.

Additional Information

Steven P. Treon, MD, PhD

Dana-Farber Cancer Institute

Phone: 617-632-2681

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place