Trial Outcomes & Findings for Rituximab, Cyclophosphamide, Bortezomib, and Dexamethasone in Treating Patients With Relapsed or Refractory Low-Grade Follicular Lymphoma, Waldenstrom Macroglobulinemia, or Mantle Cell Lymphoma (NCT NCT00711828)

NCT ID: NCT00711828

Last Updated: 2019-04-16

Results Overview

A response is defined to be a Complete Response (CR) or Partial Response (PR) noted as the objective status on any evaluation (i.e., best response). The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. A confidence interval for the true success proportion will be calculated according to the properties of the binomial distribution.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

21 participants

Primary outcome timeframe

up to 12 cycles

Results posted on

2019-04-16

Participant Flow

Participant milestones

Participant milestones
Measure
Treatment
Rituximab 375 mg/m2 IV on day 1\> Cyclophosphamide 300 mg/m2 PO on days 1, 8, 15, 22\> Bortezomib 1.3 mg/m2 IV on days 1, 8, 15, 22\> Dexamethasone 40 mg PO on days 1, 8, 15, 22
Overall Study
STARTED
21
Overall Study
COMPLETED
21
Overall Study
NOT COMPLETED
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Rituximab, Cyclophosphamide, Bortezomib, and Dexamethasone in Treating Patients With Relapsed or Refractory Low-Grade Follicular Lymphoma, Waldenstrom Macroglobulinemia, or Mantle Cell Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Treatment
n=21 Participants
Rituximab 375 mg/m2 IV on day 1\> Cyclophosphamide 300 mg/m2 PO on days 1, 8, 15, 22\> Bortezomib 1.3 mg/m2 IV on days 1, 8, 15, 22\> Dexamethasone 40 mg PO on days 1, 8, 15, 22
Age, Continuous
69 years
n=5 Participants
Sex: Female, Male
Female
8 Participants
n=5 Participants
Sex: Female, Male
Male
13 Participants
n=5 Participants
Region of Enrollment
United States
21 participants
n=5 Participants

PRIMARY outcome

Timeframe: up to 12 cycles

A response is defined to be a Complete Response (CR) or Partial Response (PR) noted as the objective status on any evaluation (i.e., best response). The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. A confidence interval for the true success proportion will be calculated according to the properties of the binomial distribution.

Outcome measures

Outcome measures
Measure
Treatment
n=21 Participants
Rituximab 375 mg/m2 IV on day 1 \> Cyclophosphamide 300 mg/m2 PO on days 1, 8, 15, 22 \> Bortezomib 1.3 mg/m2 IV on days 1, 8, 15, 22 \> Dexamethasone 40 mg PO on days 1, 8, 15, 22
Proportion of Responses (Complete Response or Partial Response)
Complete Response (CR)
19.0 percentage of participants
Interval 5.5 to 41.9
Proportion of Responses (Complete Response or Partial Response)
Partial Response (PR)
42.9 percentage of participants
Interval 21.8 to 66.0

SECONDARY outcome

Timeframe: Up to 3 years from registration

Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.

Outcome measures

Outcome measures
Measure
Treatment
n=21 Participants
Rituximab 375 mg/m2 IV on day 1 \> Cyclophosphamide 300 mg/m2 PO on days 1, 8, 15, 22 \> Bortezomib 1.3 mg/m2 IV on days 1, 8, 15, 22 \> Dexamethasone 40 mg PO on days 1, 8, 15, 22
Overall Survival
54.8 months
Interval 24.6 to 54.8

SECONDARY outcome

Timeframe: Up to 3 years from registration

Progression-free survival time is defined as the time from registration to the earliest date of documentation of disease progression or death, whichever occurs first. Progression is defines as having any new lesion or increase by 50% of previously involved sites from nadir. The distribution of progression-free survival time will be estimated using the method of Kaplan-Meier.

Outcome measures

Outcome measures
Measure
Treatment
n=21 Participants
Rituximab 375 mg/m2 IV on day 1 \> Cyclophosphamide 300 mg/m2 PO on days 1, 8, 15, 22 \> Bortezomib 1.3 mg/m2 IV on days 1, 8, 15, 22 \> Dexamethasone 40 mg PO on days 1, 8, 15, 22
Progression-free Survival
11.6 months
Interval 3.8 to
The 95% upper confidence limit was not reached.

SECONDARY outcome

Timeframe: Up to 3 years from registration

Population: Thirteen patients achieved a CR or a PR and are included in this analysis.

Duration of response is defined for all evaluable patients who have achieved an objective response as the date at which the patient's earliest objective status is first noted to be either a CR or PR to the earliest date progression is documented. MR for Waldenstrom lymphoma will not be included as a response. Median duration of response and the confidence interval for the median duration will be computed.

Outcome measures

Outcome measures
Measure
Treatment
n=13 Participants
Rituximab 375 mg/m2 IV on day 1 \> Cyclophosphamide 300 mg/m2 PO on days 1, 8, 15, 22 \> Bortezomib 1.3 mg/m2 IV on days 1, 8, 15, 22 \> Dexamethasone 40 mg PO on days 1, 8, 15, 22
Duration of Response
25.9 months
Interval 8.0 to
The 95% upper confidence limit was not reached.

SECONDARY outcome

Timeframe: Up to 3 years from registration

Time to treatment failure is defined to be the time from registration to the date at which the patient is removed from treatment due to progression, adverse events, or refusal. If the patient is considered to be a major treatment violation or is taken off study as a non-protocol failure, the patient will be censored on the date they are removed from treatment. The distribution of time to treatment failure will be estimated using the method of Kaplan-Meier.

Outcome measures

Outcome measures
Measure
Treatment
n=21 Participants
Rituximab 375 mg/m2 IV on day 1 \> Cyclophosphamide 300 mg/m2 PO on days 1, 8, 15, 22 \> Bortezomib 1.3 mg/m2 IV on days 1, 8, 15, 22 \> Dexamethasone 40 mg PO on days 1, 8, 15, 22
Time to Treatment Failure
6.6 months
Interval 2.0 to 11.6

SECONDARY outcome

Timeframe: up to 12 cycles (28 days per cycle) of treatment

Adverse events were assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 after each cycle of treatment. The maximum grade for each type of adverse event were recorded for each patient, and frequency tables were reviewed to determine patterns. For this endpoint, the number of patients receiving a Grade 3, Grade 4, or Grade 5 as their highest reported grade regardless of attribution are reported. A full list of adverse events are reported in the Adverse Events section of this report.

Outcome measures

Outcome measures
Measure
Treatment
n=21 Participants
Rituximab 375 mg/m2 IV on day 1 \> Cyclophosphamide 300 mg/m2 PO on days 1, 8, 15, 22 \> Bortezomib 1.3 mg/m2 IV on days 1, 8, 15, 22 \> Dexamethasone 40 mg PO on days 1, 8, 15, 22
Adverse Events
Grade 3
19 participants
Adverse Events
Grade 4
8 participants
Adverse Events
Grade 5
0 participants

Adverse Events

Treatment

Serious events: 7 serious events
Other events: 21 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Treatment
n=21 participants at risk
Dexamethasone 40 mg PO on days 1, 8, 15, 22
Blood and lymphatic system disorders
Hemoglobin decreased
4.8%
1/21 • Number of events 1
Cardiac disorders
Left ventricular failure
4.8%
1/21 • Number of events 1
Cardiac disorders
Restrictive cardiomyopathy
4.8%
1/21 • Number of events 1
Gastrointestinal disorders
Abdominal pain
4.8%
1/21 • Number of events 1
Infections and infestations
Appendicitis
4.8%
1/21 • Number of events 1
Infections and infestations
Encephalomyelitis infection
4.8%
1/21 • Number of events 1
Investigations
Leukocyte count decreased
14.3%
3/21 • Number of events 4
Investigations
Platelet count decreased
9.5%
2/21 • Number of events 3
Nervous system disorders
Peripheral sensory neuropathy
4.8%
1/21 • Number of events 1

Other adverse events

Other adverse events
Measure
Treatment
n=21 participants at risk
Dexamethasone 40 mg PO on days 1, 8, 15, 22
Blood and lymphatic system disorders
Hemoglobin decreased
85.7%
18/21 • Number of events 105
Cardiac disorders
Cardiac pain
4.8%
1/21 • Number of events 1
Gastrointestinal disorders
Abdominal pain
9.5%
2/21 • Number of events 2
Gastrointestinal disorders
Constipation
14.3%
3/21 • Number of events 3
Gastrointestinal disorders
Diarrhea
38.1%
8/21 • Number of events 15
Gastrointestinal disorders
Gastritis
4.8%
1/21 • Number of events 5
Gastrointestinal disorders
Nausea
14.3%
3/21 • Number of events 3
Gastrointestinal disorders
Vomiting
4.8%
1/21 • Number of events 1
General disorders
Fatigue
95.2%
20/21 • Number of events 111
General disorders
Fever
4.8%
1/21 • Number of events 1
Immune system disorders
Hypersensitivity
4.8%
1/21 • Number of events 1
Infections and infestations
Infectious colitis
4.8%
1/21 • Number of events 1
Infections and infestations
Pneumonia
4.8%
1/21 • Number of events 1
Infections and infestations
Skin infection
9.5%
2/21 • Number of events 3
Infections and infestations
Upper respiratory infection
4.8%
1/21 • Number of events 2
Investigations
Leukocyte count decreased
81.0%
17/21 • Number of events 63
Investigations
Lymphocyte count decreased
4.8%
1/21 • Number of events 4
Investigations
Neutrophil count decreased
57.1%
12/21 • Number of events 33
Investigations
Platelet count decreased
66.7%
14/21 • Number of events 66
Metabolism and nutrition disorders
Anorexia
4.8%
1/21 • Number of events 1
Metabolism and nutrition disorders
Blood glucose increased
4.8%
1/21 • Number of events 1
Metabolism and nutrition disorders
Serum potassium increased
4.8%
1/21 • Number of events 1
Metabolism and nutrition disorders
Tumor lysis syndrome
4.8%
1/21 • Number of events 1
Musculoskeletal and connective tissue disorders
Arthritis
4.8%
1/21 • Number of events 1
Musculoskeletal and connective tissue disorders
Back pain
4.8%
1/21 • Number of events 1
Musculoskeletal and connective tissue disorders
Myalgia
4.8%
1/21 • Number of events 1
Nervous system disorders
Peripheral motor neuropathy
4.8%
1/21 • Number of events 1
Nervous system disorders
Peripheral sensory neuropathy
81.0%
17/21 • Number of events 97
Nervous system disorders
Taste alteration
4.8%
1/21 • Number of events 1
Psychiatric disorders
Agitation
9.5%
2/21 • Number of events 8
Psychiatric disorders
Anxiety
14.3%
3/21 • Number of events 4
Psychiatric disorders
Depression
4.8%
1/21 • Number of events 1
Psychiatric disorders
Insomnia
4.8%
1/21 • Number of events 9
Renal and urinary disorders
Cystitis
4.8%
1/21 • Number of events 1
Respiratory, thoracic and mediastinal disorders
Dyspnea
14.3%
3/21 • Number of events 3
Respiratory, thoracic and mediastinal disorders
Pleural effusion
4.8%
1/21 • Number of events 1
Vascular disorders
Hypotension
4.8%
1/21 • Number of events 1

Additional Information

Craig B. Reeder, M.D.

Mayo Clinic

Results disclosure agreements

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