Trial Outcomes & Findings for Bortezomib and Rituximab for Patients With Waldenstrom's Macroglobulinemia (NCT NCT00492050)

NCT ID: NCT00492050

Last Updated: 2025-09-02

Results Overview

Partial response (PR) defined as at least \> 50 % reduction of serum monoclonal IgM concentration determined by protein electrophoresis, \> 50% decrease in adenopathy / organomegaly on physical examination or on CT scan, and no new symptoms or signs of active disease. Complete response (CR) defined as a disappearance of serum and urine monoclonal protein determined by immunofixation, absence of malignant cells in bone marrow determined by histologic evaluation, resolution of adenopathy/organomegaly (confirmed by computed tomography \[CT\] scan), and no signs or symptoms attributable to WM. Stable disease defined as neither grown nor shrunk; the amount of disease has not changed.Participants will be followed for \< 6 months after receiving bortezomib/rituximab or rituximab-modified hyper-CVAD to be considered unresponsive to therapy in accordance with the guidelines of the Consensus Panel of the Third International Workshop on Waldenstrom's Macroglobulinemia.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

46 participants

Primary outcome timeframe

After 2 (35 day) cycles of treatment

Results posted on

2025-09-02

Participant Flow

Recruitment Period: August 2006- March 2013

46 Participants consented, 9 screen failures.

Participant milestones

Participant milestones
Measure
Bortezomib + Rituximab
Bortezomib 1.6 mg/m\^2 IV Weekly on Days 1, 8, 15 and 22. Rituximab 375 mg/m\^2 IV on Day 8 and 22. Valacyclovir 500 mg orally daily (or acyclovir 200 mg orally twice daily). Bortezomib: 1.6 mg/m\^2 IV Weekly on Days 1, 8, 15 and 22. Rituximab: 375 mg/m\^2 IV on Day 8 and 22. Valacyclovir: 500 mg orally daily (or acyclovir 200 mg orally twice daily)
Overall Study
STARTED
37
Overall Study
Inadequate Response to First Two Cycles
25
Overall Study
Inadequate Response to First 3 Cycles
12
Overall Study
If Adequate Response to First Two Cycles-participants Proceed to Stem Cell Collection
30
Overall Study
COMPLETED
28
Overall Study
NOT COMPLETED
9

Reasons for withdrawal

Reasons for withdrawal
Measure
Bortezomib + Rituximab
Bortezomib 1.6 mg/m\^2 IV Weekly on Days 1, 8, 15 and 22. Rituximab 375 mg/m\^2 IV on Day 8 and 22. Valacyclovir 500 mg orally daily (or acyclovir 200 mg orally twice daily). Bortezomib: 1.6 mg/m\^2 IV Weekly on Days 1, 8, 15 and 22. Rituximab: 375 mg/m\^2 IV on Day 8 and 22. Valacyclovir: 500 mg orally daily (or acyclovir 200 mg orally twice daily)
Overall Study
Adverse Event
1
Overall Study
Lack of Efficacy
1
Overall Study
Withdrawal by Subject
3
Overall Study
Unable to collect SCT
2
Overall Study
Progressive Disease
2

Baseline Characteristics

Bortezomib and Rituximab for Patients With Waldenstrom's Macroglobulinemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
All Participants
n=37 Participants
Bortezomib 1.6 mg/m\^2 IV Weekly on Days 1, 8, 15 and 22. Rituximab 375 mg/m\^2 IV on Day 8 and 22. Valacyclovir 500 mg orally daily (or acyclovir 200 mg orally twice daily). Bortezomib: 1.6 mg/m\^2 IV Weekly on Days 1, 8, 15 and 22. Rituximab: 375 mg/m\^2 IV on Day 8 and 22. Valacyclovir: 500 mg orally daily (or acyclovir 200 mg orally twice daily)
Age, Categorical
<=18 years
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
28 Participants
n=5 Participants
Age, Categorical
>=65 years
9 Participants
n=5 Participants
Age, Continuous
61 years
n=5 Participants
Sex: Female, Male
Female
9 Participants
n=5 Participants
Sex: Female, Male
Male
28 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
2 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
35 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
2 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
3 Participants
n=5 Participants
Race (NIH/OMB)
White
30 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
2 Participants
n=5 Participants
Region of Enrollment
United States
37 participants
n=5 Participants
Newly diagnosed patient with Waldenstrom Macroglobulinemia with no prior treatment
37 Participants
n=5 Participants

PRIMARY outcome

Timeframe: After 2 (35 day) cycles of treatment

Population: 1 subject didn't complete 2 cycles of therapy and isn't evaluable for response

Partial response (PR) defined as at least \> 50 % reduction of serum monoclonal IgM concentration determined by protein electrophoresis, \> 50% decrease in adenopathy / organomegaly on physical examination or on CT scan, and no new symptoms or signs of active disease. Complete response (CR) defined as a disappearance of serum and urine monoclonal protein determined by immunofixation, absence of malignant cells in bone marrow determined by histologic evaluation, resolution of adenopathy/organomegaly (confirmed by computed tomography \[CT\] scan), and no signs or symptoms attributable to WM. Stable disease defined as neither grown nor shrunk; the amount of disease has not changed.Participants will be followed for \< 6 months after receiving bortezomib/rituximab or rituximab-modified hyper-CVAD to be considered unresponsive to therapy in accordance with the guidelines of the Consensus Panel of the Third International Workshop on Waldenstrom's Macroglobulinemia.

Outcome measures

Outcome measures
Measure
All Participants
n=36 Participants
Bortezomib 1.6 mg/m\^2 IV Weekly on Days 1, 8, 15 and 22. Rituximab 375 mg/m\^2 IV on Day 8 and 22. Valacyclovir 500 mg orally daily (or acyclovir 200 mg orally twice daily). Bortezomib: 1.6 mg/m\^2 IV Weekly on Days 1, 8, 15 and 22. Rituximab: 375 mg/m\^2 IV on Day 8 and 22. Valacyclovir: 500 mg orally daily (or acyclovir 200 mg orally twice daily)
Response Rate After 2 Cycles of Treatment With Bortezomib and Rituximab
Stable Disease
20 Participants
Response Rate After 2 Cycles of Treatment With Bortezomib and Rituximab
Partial Response
11 Participants
Response Rate After 2 Cycles of Treatment With Bortezomib and Rituximab
Progressive Disease
2 Participants
Response Rate After 2 Cycles of Treatment With Bortezomib and Rituximab
No Response
3 Participants

PRIMARY outcome

Timeframe: After 3 (35 day) cycles of treatment

Partial response (PR) defined as at least \> 50 % reduction of serum monoclonal IgM concentration determined by protein electrophoresis, \> 50% decrease in adenopathy / organomegaly on physical examination or on CT scan, and no new symptoms or signs of active disease. Complete response (CR) defined as a disappearance of serum and urine monoclonal protein determined by immunofixation, absence of malignant cells in bone marrow determined by histologic evaluation, resolution of adenopathy/organomegaly (confirmed by computed tomography \[CT\] scan), and no signs or symptoms attributable to WM. Stable disease defined as neither grown nor shrunk; the amount of disease has not changed. Participants will be followed for \< 6 months after receiving bortezomib/rituximab or rituximab-modified hyper-CVAD to be considered unresponsive to therapy in accordance with the guidelines of the Consensus Panel of the Third International Workshop on Waldenstrom's Macroglobulinemia.

Outcome measures

Outcome measures
Measure
All Participants
n=25 Participants
Bortezomib 1.6 mg/m\^2 IV Weekly on Days 1, 8, 15 and 22. Rituximab 375 mg/m\^2 IV on Day 8 and 22. Valacyclovir 500 mg orally daily (or acyclovir 200 mg orally twice daily). Bortezomib: 1.6 mg/m\^2 IV Weekly on Days 1, 8, 15 and 22. Rituximab: 375 mg/m\^2 IV on Day 8 and 22. Valacyclovir: 500 mg orally daily (or acyclovir 200 mg orally twice daily)
Response Rate After 3 Cycles of Treatment With Bortezomib and Rituximab
Stable Disease
7 Participants
Response Rate After 3 Cycles of Treatment With Bortezomib and Rituximab
Partial Response
16 Participants
Response Rate After 3 Cycles of Treatment With Bortezomib and Rituximab
No Response
2 Participants

PRIMARY outcome

Timeframe: 4 weeks

Number of Participants who were able to collect stem cells successfully or unable to collect after treatment with bortezomib and rituximab.

Outcome measures

Outcome measures
Measure
All Participants
n=37 Participants
Bortezomib 1.6 mg/m\^2 IV Weekly on Days 1, 8, 15 and 22. Rituximab 375 mg/m\^2 IV on Day 8 and 22. Valacyclovir 500 mg orally daily (or acyclovir 200 mg orally twice daily). Bortezomib: 1.6 mg/m\^2 IV Weekly on Days 1, 8, 15 and 22. Rituximab: 375 mg/m\^2 IV on Day 8 and 22. Valacyclovir: 500 mg orally daily (or acyclovir 200 mg orally twice daily)
Participants Ability to Collect Stem Cells After Treatment With Bortezomib and Rituximab
Participants Collected Successfully
30 Participants
Participants Ability to Collect Stem Cells After Treatment With Bortezomib and Rituximab
Participants Unable to Collect
7 Participants

Adverse Events

All Participants

Serious events: 14 serious events
Other events: 14 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
All Participants
n=37 participants at risk
Bortezomib 1.6 mg/m\^2 IV Weekly on Days 1, 8, 15 and 22. Rituximab 375 mg/m\^2 IV on Day 8 and 22. Valacyclovir 500 mg orally daily (or acyclovir 200 mg orally twice daily). Bortezomib: 1.6 mg/m\^2 IV Weekly on Days 1, 8, 15 and 22. Rituximab: 375 mg/m\^2 IV on Day 8 and 22. Valacyclovir: 500 mg orally daily (or acyclovir 200 mg orally twice daily)
Blood and lymphatic system disorders
Anemia
5.4%
2/37 • From the first dose through 30 days after the last dosage up to 5 years
Cardiac disorders
Hypotension
5.4%
2/37 • From the first dose through 30 days after the last dosage up to 5 years
Gastrointestinal disorders
Diarrhea
2.7%
1/37 • From the first dose through 30 days after the last dosage up to 5 years
Gastrointestinal disorders
Elevated Alkaline Phosphate
2.7%
1/37 • From the first dose through 30 days after the last dosage up to 5 years
Infections and infestations
Fever
2.7%
1/37 • From the first dose through 30 days after the last dosage up to 5 years
Infections and infestations
Gram negative bacteremia
2.7%
1/37 • From the first dose through 30 days after the last dosage up to 5 years
Metabolism and nutrition disorders
Hypercalcemia
2.7%
1/37 • From the first dose through 30 days after the last dosage up to 5 years
Blood and lymphatic system disorders
Neutropenia
2.7%
1/37 • From the first dose through 30 days after the last dosage up to 5 years
Infections and infestations
Neutrophenic fever
2.7%
1/37 • From the first dose through 30 days after the last dosage up to 5 years
Respiratory, thoracic and mediastinal disorders
Pleural effusion
2.7%
1/37 • From the first dose through 30 days after the last dosage up to 5 years
Respiratory, thoracic and mediastinal disorders
Pneumonia
2.7%
1/37 • From the first dose through 30 days after the last dosage up to 5 years
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
2.7%
1/37 • From the first dose through 30 days after the last dosage up to 5 years
Respiratory, thoracic and mediastinal disorders
Pulmonary nodules
2.7%
1/37 • From the first dose through 30 days after the last dosage up to 5 years
Infections and infestations
Spetic shock
2.7%
1/37 • From the first dose through 30 days after the last dosage up to 5 years
Respiratory, thoracic and mediastinal disorders
Shortness of breath
2.7%
1/37 • From the first dose through 30 days after the last dosage up to 5 years
General disorders
Visual changes
2.7%
1/37 • From the first dose through 30 days after the last dosage up to 5 years
Blood and lymphatic system disorders
Hyperviscosity
2.7%
1/37 • From the first dose through 30 days after the last dosage up to 5 years

Other adverse events

Other adverse events
Measure
All Participants
n=37 participants at risk
Bortezomib 1.6 mg/m\^2 IV Weekly on Days 1, 8, 15 and 22. Rituximab 375 mg/m\^2 IV on Day 8 and 22. Valacyclovir 500 mg orally daily (or acyclovir 200 mg orally twice daily). Bortezomib: 1.6 mg/m\^2 IV Weekly on Days 1, 8, 15 and 22. Rituximab: 375 mg/m\^2 IV on Day 8 and 22. Valacyclovir: 500 mg orally daily (or acyclovir 200 mg orally twice daily)
General disorders
Fatigue
16.2%
6/37 • From the first dose through 30 days after the last dosage up to 5 years
Gastrointestinal disorders
Diarrhea
8.1%
3/37 • From the first dose through 30 days after the last dosage up to 5 years
Musculoskeletal and connective tissue disorders
Pain (joint)
10.8%
4/37 • From the first dose through 30 days after the last dosage up to 5 years
Musculoskeletal and connective tissue disorders
Pain (muscle)
10.8%
4/37 • From the first dose through 30 days after the last dosage up to 5 years
Blood and lymphatic system disorders
Neutropenia
10.8%
4/37 • From the first dose through 30 days after the last dosage up to 5 years
Nervous system disorders
Dizziness
5.4%
2/37 • From the first dose through 30 days after the last dosage up to 5 years
Gastrointestinal disorders
Vomiting
5.4%
2/37 • From the first dose through 30 days after the last dosage up to 5 years
Renal and urinary disorders
BUN increase
2.7%
1/37 • From the first dose through 30 days after the last dosage up to 5 years
Renal and urinary disorders
Creatinine increase
2.7%
1/37 • From the first dose through 30 days after the last dosage up to 5 years
Eye disorders
Dry eye
8.1%
3/37 • From the first dose through 30 days after the last dosage up to 5 years
Respiratory, thoracic and mediastinal disorders
Dyspnea
5.4%
2/37 • From the first dose through 30 days after the last dosage up to 5 years
Vascular disorders
Peripheral Edema
2.7%
1/37 • From the first dose through 30 days after the last dosage up to 5 years
Blood and lymphatic system disorders
Leukopenia
8.1%
3/37 • From the first dose through 30 days after the last dosage up to 5 years
Musculoskeletal and connective tissue disorders
Myalgia
2.7%
1/37 • From the first dose through 30 days after the last dosage up to 5 years
Nervous system disorders
Neuopathy
2.7%
1/37 • From the first dose through 30 days after the last dosage up to 5 years
Respiratory, thoracic and mediastinal disorders
Pleural effusion
2.7%
1/37 • From the first dose through 30 days after the last dosage up to 5 years

Additional Information

Sheeba Thomas, MD-Professor, Lymphoma-Myeloma

UT MD Anderson Cancer Center

Phone: (713) 792-2860

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place