Trial Outcomes & Findings for Study of the Combination of Bortezomib, Dexamethasone, and Rituximab in Patients With Waldenstroms Macroglobulinemia (NCT NCT00250926)

Last Updated: 2016-04-08

Results Overview

This outcome measure was to assess the safety and tolerability of bortezomib, dexamethasone and rituximab in patients with untreated Waldenstroms macroglobulinemia.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

23 participants

Primary outcome timeframe

33.2 months

Results posted on

2016-04-08

Participant Flow

Outpatient clinic at DFCI

Symptomatic patients with Waldenstrom's requiring therapy, previously untreated.

Participant milestones

Participant milestones
Measure	Bortezomib, Dexamethasone, Rituximab A cycle of therapy consisted of bortezomib 1.3 mg/m(2) intravenously; dexamethasone 40 mg on days 1, 4, 8, and 11; and rituximab 375 mg/m(2) on day 11. Patients received four consecutive cycles for induction therapy and then four more cycles, each given 3 months apart, for maintenance therapy.
Overall Study STARTED	23
Overall Study COMPLETED	23
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of the Combination of Bortezomib, Dexamethasone, and Rituximab in Patients With Waldenstroms Macroglobulinemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bortezomib, Dexamethasone, Rituximab n=23 Participants A cycle of therapy consisted of bortezomib 1.3 mg/m(2) intravenously; dexamethasone 40 mg on days 1, 4, 8, and 11; and rituximab 375 mg/m(2) on day 11. Patients received four consecutive cycles for induction therapy and then four more cycles, each given 3 months apart, for maintenance therapy.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=5 Participants
Age, Categorical >=65 years	13 Participants n=5 Participants
Age, Continuous	67 years STANDARD_DEVIATION 10 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants
Region of Enrollment United States	23 participants n=5 Participants

PRIMARY outcome

Timeframe: 33.2 months

Population: All enrolled patients

This outcome measure was to assess the safety and tolerability of bortezomib, dexamethasone and rituximab in patients with untreated Waldenstroms macroglobulinemia.

Outcome measures

Outcome measures
Measure	Bortezomib, Dexamethasone, Rituximab n=23 Participants A cycle of therapy consisted of bortezomib 1.3 mg/m(2) intravenously; dexamethasone 40 mg on days 1, 4, 8, and 11; and rituximab 375 mg/m(2) on day 11. Patients received four consecutive cycles for induction therapy and then four more cycles, each given 3 months apart, for maintenance therapy.
Number of Participants With Adverse Events	23 participants

PRIMARY outcome

Timeframe: 33.2 months

Population: all enrolled patients

This outcome measure was to determine the response rate along with attainment of stable disease and time to disease progression following treatment with this patient population. The response rates were defined as follows. A complete response (CR) was defined as having resolution of all symptoms, normalization of serum IgM levels with complete disappearance of IgM paraprotein by immunofixation, absence of bone marrow disease by bone marrow biopsy and aspiration, and resolution of any adenopathy or splenomegaly. A near complete response (nCR) was defined as fulfilling all CR criteria in the presence of a positive immunofixation study. Patients with very good partial response (VGPR), partial response (PR), and minor response (MR) were defined as having a ≥ 90%, ≥ 50%, and 25% to 49% reduction in serum IgM levels, respectively. Progressive disease (PD) occurred when a more than 25% increase in serum IgM level or progression of clinically significant disease parameters was observed.

Outcome measures

Outcome measures
Measure	Bortezomib, Dexamethasone, Rituximab n=23 Participants A cycle of therapy consisted of bortezomib 1.3 mg/m(2) intravenously; dexamethasone 40 mg on days 1, 4, 8, and 11; and rituximab 375 mg/m(2) on day 11. Patients received four consecutive cycles for induction therapy and then four more cycles, each given 3 months apart, for maintenance therapy.
Response Rate Complete Response (CR)	3 participants
Response Rate Near Complete Response (nCR)	2 participants
Response Rate Very Good Partial Response (VGPR)	3 participants
Response Rate Partial Response (PR)	11 participants
Response Rate Minor Response (MR)	3 participants
Response Rate Stable Disease	1 participants

PRIMARY outcome

Timeframe: 33.2 months

Outcome measures

Outcome measures
Measure	Bortezomib, Dexamethasone, Rituximab n=23 Participants A cycle of therapy consisted of bortezomib 1.3 mg/m(2) intravenously; dexamethasone 40 mg on days 1, 4, 8, and 11; and rituximab 375 mg/m(2) on day 11. Patients received four consecutive cycles for induction therapy and then four more cycles, each given 3 months apart, for maintenance therapy.
Time to Best Response	15 Months Interval 0.7 to 26.0

PRIMARY outcome

Timeframe: 42 months

Population: The median time to progression was not achieved as follow-up ended before half the participants had a PD event.

Progressive Disease (PD) will be defined as a greater than 25% increase in serum IgM monoclonal protein levels 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	Bortezomib, Dexamethasone, Rituximab n=23 Participants A cycle of therapy consisted of bortezomib 1.3 mg/m(2) intravenously; dexamethasone 40 mg on days 1, 4, 8, and 11; and rituximab 375 mg/m(2) on day 11. Patients received four consecutive cycles for induction therapy and then four more cycles, each given 3 months apart, for maintenance therapy.
Time to Progression	NA months Interval 6.0 to The median time to progression was not met before the follow-up time for the protocol was complete. Most patients had not had a PD event at the 42 month cut-off.

Adverse Events

Bortezomib, Dexamethasone, Rituximab

Serious events: 19 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Bortezomib, Dexamethasone, Rituximab n=23 participants at risk A cycle of therapy consisted of bortezomib 1.3 mg/m(2) intravenously; dexamethasone 40 mg on days 1, 4, 8, and 11; and rituximab 375 mg/m(2) on day 11. Patients received four consecutive cycles for induction therapy and then four more cycles, each given 3 months apart, for maintenance therapy.
Nervous system disorders Peripheral Neuropathy	30.4% 7/23 • Number of events 7
Blood and lymphatic system disorders Neutropenia	26.1% 6/23 • Number of events 6
Blood and lymphatic system disorders thrombocytopenia	8.7% 2/23 • Number of events 2
Musculoskeletal and connective tissue disorders myopathy	4.3% 1/23 • Number of events 1
Respiratory, thoracic and mediastinal disorders Pneumonia	4.3% 1/23 • Number of events 1
Blood and lymphatic system disorders Infection with Neutropenia	4.3% 1/23 • Number of events 1
General disorders hypotension	4.3% 1/23 • Number of events 1
Cardiac disorders arrythmia	4.3% 1/23 • Number of events 1
Blood and lymphatic system disorders anemia	4.3% 1/23 • Number of events 1

Other adverse events

Other adverse events
Measure	Bortezomib, Dexamethasone, Rituximab n=23 participants at risk A cycle of therapy consisted of bortezomib 1.3 mg/m(2) intravenously; dexamethasone 40 mg on days 1, 4, 8, and 11; and rituximab 375 mg/m(2) on day 11. Patients received four consecutive cycles for induction therapy and then four more cycles, each given 3 months apart, for maintenance therapy.
Nervous system disorders Peripheral Neuropathy	39.1% 9/23 • Number of events 9
Infections and infestations Infection without Neutropenia	43.5% 10/23 • Number of events 10
Blood and lymphatic system disorders Anemia	78.3% 18/23 • Number of events 18
Blood and lymphatic system disorders Thrombocytopenia	34.8% 8/23 • Number of events 8
Cardiac disorders neutropenia	26.1% 6/23 • Number of events 6
Endocrine disorders hyeprglycemia	26.1% 6/23 • Number of events 6
Infections and infestations herpes zoster	21.7% 5/23 • Number of events 5
Respiratory, thoracic and mediastinal disorders Pneumonia	8.7% 2/23 • Number of events 2
General disorders Fatigue	17.4% 4/23 • Number of events 4
General disorders Insomnia	13.0% 3/23 • Number of events 3
Respiratory, thoracic and mediastinal disorders dyspnea	13.0% 3/23 • Number of events 3
General disorders dehydration	13.0% 3/23 • Number of events 3
Respiratory, thoracic and mediastinal disorders cough	13.0% 3/23 • Number of events 3
Cardiac disorders arrythmia	8.7% 2/23 • Number of events 2

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