Trial Outcomes & Findings for Lenalidomide, Rituximab, Cyclophosphamide, and Dexamethasone in Treating Patients With Previously Untreated Low-Grade Non-Hodgkin Lymphoma (NCT NCT00784927)

NCT ID: NCT00784927

Last Updated: 2016-10-07

Results Overview

The proportion of responses was determined by counting the number of complete responses and partial responses and dividing by the number of evaluable patients. Complete Response (CR): Disappearance of all evidence of disease and disease-related symptoms. The spleen and/or liver, if considered enlarged before therapy on the basis of a physical examination or CT scan, should not be palpable on physical examination and should be considered normal size by imaging studies, and nodules related to lymphoma should disappear. If the bone marrow was involved by lymphoma before treatment, the infiltrate must have cleared on repeat bone marrow biopsy. Partial Response (PR): At least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses. No increase should be observed in the size of other nodes, liver, or spleen. No new sites of disease should be observed.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 36 participants
• Primary outcome timeframe: Up to 1 year from registration.
• Results posted on: 2016-10-07

Participant Flow

Participant milestones

Measure	Treatment Participants with symptomatic untreated low grade NHL will be treated according to a 28 day schedule for up to a maximum of 12 consecutive cycles: 375 mg/m\^2 Rituximab IV on day 1. 20 mg Lenalidomide taken orally on days 1-21. 250 mg/m\^2 Cyclophosphamide orally on days 1, 8, 15. 40 mg Dexamethasone orally on days 1, 8, 15, 22.
Overall Study STARTED	36
Overall Study COMPLETED	33
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	Treatment Participants with symptomatic untreated low grade NHL will be treated according to a 28 day schedule for up to a maximum of 12 consecutive cycles: 375 mg/m\^2 Rituximab IV on day 1. 20 mg Lenalidomide taken orally on days 1-21. 250 mg/m\^2 Cyclophosphamide orally on days 1, 8, 15. 40 mg Dexamethasone orally on days 1, 8, 15, 22.
Overall Study Cancel Prior to Initiating Treatment	1
Overall Study Protocol Violation	1
Overall Study Ineligible	1

Baseline Characteristics

Lenalidomide, Rituximab, Cyclophosphamide, and Dexamethasone in Treating Patients With Previously Untreated Low-Grade Non-Hodgkin Lymphoma

Baseline characteristics by cohort

Measure	Treatment n=33 Participants Participants with symptomatic untreated low grade NHL will be treated according to a 28 day schedule for up to a maximum of 12 consecutive cycles: 375 mg/m\^2 Rituximab IV on day 1. 20 mg Lenalidomide taken orally on days 1-21. 250 mg/m\^2 Cyclophosphamide orally on days 1, 8, 15. 40 mg Dexamethasone orally on days 1, 8, 15, 22.
Age, Continuous	68 years n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants
Region of Enrollment United States	33 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 1 year from registration.

The proportion of responses was determined by counting the number of complete responses and partial responses and dividing by the number of evaluable patients.

Complete Response (CR): Disappearance of all evidence of disease and disease-related symptoms. The spleen and/or liver, if considered enlarged before therapy on the basis of a physical examination or CT scan, should not be palpable on physical examination and should be considered normal size by imaging studies, and nodules related to lymphoma should disappear. If the bone marrow was involved by lymphoma before treatment, the infiltrate must have cleared on repeat bone marrow biopsy.

Partial Response (PR): At least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses. No increase should be observed in the size of other nodes, liver, or spleen. No new sites of disease should be observed.

Outcome measures

Measure	Treatment n=33 Participants Participants with symptomatic untreated low grade NHL will be treated according to a 28 day schedule for up to a maximum of 12 consecutive cycles: 375 mg/m\^2 Rituximab IV on day 1. 20 mg Lenalidomide taken orally on days 1-21. 250 mg/m\^2 Cyclophosphamide orally on days 1, 8, 15. 40 mg Dexamethasone orally on days 1, 8, 15, 22.
Assessment of Tumor Response Complete Response (CR)	30.3 percentage of participants Interval 15.6 to 48.7
Assessment of Tumor Response Partial Response (PR)	54.5 percentage of participants Interval 36.4 to 71.9

SECONDARY outcome

Timeframe: Up to 1 year from registration.

The proportion of responses in Waldenstrom's macroglobulinemia was determined by counting the number of complete responses and partial responses and dividing by the number of evaluable patients.

Complete Response (CR): Disappearance of all evidence of disease and disease-related symptoms. The spleen and/or liver, if considered enlarged before therapy on the basis of a physical examination or CT scan, should not be palpable on physical examination and should be considered normal size by imaging studies, and nodules related to lymphoma should disappear. If the bone marrow was involved by lymphoma before treatment, the infiltrate must have cleared on repeat bone marrow biopsy.

Partial Response (PR): At least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses. No increase should be observed in the size of other nodes, liver, or spleen. No new sites of disease should be observed.

Outcome measures

Measure	Treatment n=15 Participants Participants with symptomatic untreated low grade NHL will be treated according to a 28 day schedule for up to a maximum of 12 consecutive cycles: 375 mg/m\^2 Rituximab IV on day 1. 20 mg Lenalidomide taken orally on days 1-21. 250 mg/m\^2 Cyclophosphamide orally on days 1, 8, 15. 40 mg Dexamethasone orally on days 1, 8, 15, 22.
Tumor Response to Lenalidomide, Rituximab, Cyclophosphamide and Dexamethasone in the Subgroup of Patients With Lymphoplasmacytic Lymphoma (Waldenstrom's Macroglobulinemia). Complete Response (CR)	6.7 percentage of participants Interval 0.2 to 32.0
Tumor Response to Lenalidomide, Rituximab, Cyclophosphamide and Dexamethasone in the Subgroup of Patients With Lymphoplasmacytic Lymphoma (Waldenstrom's Macroglobulinemia). Partial Response (PR)	66.7 percentage of participants Interval 38.4 to 88.2

SECONDARY outcome

Timeframe: Up to 1 year 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

Measure	Treatment n=33 Participants Participants with symptomatic untreated low grade NHL will be treated according to a 28 day schedule for up to a maximum of 12 consecutive cycles: 375 mg/m\^2 Rituximab IV on day 1. 20 mg Lenalidomide taken orally on days 1-21. 250 mg/m\^2 Cyclophosphamide orally on days 1, 8, 15. 40 mg Dexamethasone orally on days 1, 8, 15, 22.
Survival Time	NA months The median overall survival time and the upper and lower confidence limits were not reached.

SECONDARY outcome

Timeframe: Up to 1 year from registration.

Progression-free survival time is defined as the time from registration to the earliest date of documentation of disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had disease progression at the time of their death.

Progressive disease is defined as having one of the following:

• The appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size.
• At least a 50% increase from nadir in the sum of the product of the dimension (SPD) of any previously involved nodes.
• At least a 50% increase in the longest diameter of any single previously identified node more than 1 cm in its short axis.

Outcome measures

Measure	Treatment n=33 Participants Participants with symptomatic untreated low grade NHL will be treated according to a 28 day schedule for up to a maximum of 12 consecutive cycles: 375 mg/m\^2 Rituximab IV on day 1. 20 mg Lenalidomide taken orally on days 1-21. 250 mg/m\^2 Cyclophosphamide orally on days 1, 8, 15. 40 mg Dexamethasone orally on days 1, 8, 15, 22.
Progression-free Survival Time	38.3 months Interval 25.2 to The 95% upper confidence limit was not reached.

SECONDARY outcome

Timeframe: Up to 1 year 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. The distribution of time to treatment failure will be estimated using the method of Kaplan-Meier.

Outcome measures

Measure	Treatment n=33 Participants Participants with symptomatic untreated low grade NHL will be treated according to a 28 day schedule for up to a maximum of 12 consecutive cycles: 375 mg/m\^2 Rituximab IV on day 1. 20 mg Lenalidomide taken orally on days 1-21. 250 mg/m\^2 Cyclophosphamide orally on days 1, 8, 15. 40 mg Dexamethasone orally on days 1, 8, 15, 22.
Time to Treatment Failure	NA months The median time to treatment failure and the upper and lower confidence limits were not reached.

Adverse Events

Treatment

Serious events: 15 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Measure	Treatment n=33 participants at risk 40 mg Dexamethasone orally on days 1, 8, 15, 22.
Blood and lymphatic system disorders Hemoglobin decreased	18.2% 6/33 • Number of events 6
Gastrointestinal disorders Abdominal pain	3.0% 1/33 • Number of events 1
Gastrointestinal disorders Colitis	3.0% 1/33 • Number of events 1
Gastrointestinal disorders Gastrointestinal disorder	3.0% 1/33 • Number of events 1
Gastrointestinal disorders Nausea	3.0% 1/33 • Number of events 1
General disorders Fatigue	3.0% 1/33 • Number of events 1
Infections and infestations Pneumonia	6.1% 2/33 • Number of events 2
Investigations Leukocyte count decreased	3.0% 1/33 • Number of events 1
Investigations Neutrophil count decreased	9.1% 3/33 • Number of events 5
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	3.0% 1/33 • Number of events 1
Nervous system disorders Tremor	3.0% 1/33 • Number of events 1
Respiratory, thoracic and mediastinal disorders Dyspnea	3.0% 1/33 • Number of events 1
Skin and subcutaneous tissue disorders Rash desquamating	3.0% 1/33 • Number of events 1
Vascular disorders Thrombosis	9.1% 3/33 • Number of events 3
Vascular disorders Vascular disorder	3.0% 1/33 • Number of events 1
General disorders Sudden Death	3.0% 1/33 • Number of events 1

Other adverse events

Measure	Treatment n=33 participants at risk 40 mg Dexamethasone orally on days 1, 8, 15, 22.
Blood and lymphatic system disorders Hemoglobin decreased	84.8% 28/33 • Number of events 174
Cardiac disorders Sinus tachycardia	3.0% 1/33 • Number of events 1
Eye disorders Vision blurred	3.0% 1/33 • Number of events 1
Gastrointestinal disorders Constipation	3.0% 1/33 • Number of events 1
Gastrointestinal disorders Diarrhea	27.3% 9/33 • Number of events 22
Gastrointestinal disorders Dyspepsia	3.0% 1/33 • Number of events 1
Gastrointestinal disorders Esophagitis	3.0% 1/33 • Number of events 1
Gastrointestinal disorders Nausea	36.4% 12/33 • Number of events 31
Gastrointestinal disorders Oesophagoscopy abnormal	3.0% 1/33 • Number of events 1
Gastrointestinal disorders Vomiting	12.1% 4/33 • Number of events 6
General disorders Chills	3.0% 1/33 • Number of events 1
General disorders Edema limbs	45.5% 15/33 • Number of events 59
General disorders Fatigue	100.0% 33/33 • Number of events 217
General disorders Fever	3.0% 1/33 • Number of events 2
Immune system disorders Cytokine release syndrome	12.1% 4/33 • Number of events 5
Immune system disorders Hypersensitivity	6.1% 2/33 • Number of events 2
Immune system disorders Immune system disorder	3.0% 1/33 • Number of events 1
Infections and infestations Infection	3.0% 1/33 • Number of events 1
Infections and infestations Pneumonia	9.1% 3/33 • Number of events 6
Infections and infestations Tooth infection	3.0% 1/33 • Number of events 1
Injury, poisoning and procedural complications Bruising	3.0% 1/33 • Number of events 2
Injury, poisoning and procedural complications Fracture	3.0% 1/33 • Number of events 1
Investigations Alanine aminotransferase increased	3.0% 1/33 • Number of events 1
Investigations Alkaline phosphatase increased	3.0% 1/33 • Number of events 1
Investigations Aspartate aminotransferase increased	3.0% 1/33 • Number of events 1
Investigations Bilirubin increased	6.1% 2/33 • Number of events 3
Investigations Leukocyte count decreased	78.8% 26/33 • Number of events 109
Investigations Lymphocyte count decreased	3.0% 1/33 • Number of events 1
Investigations Neutrophil count decreased	84.8% 28/33 • Number of events 121
Investigations Platelet count decreased	66.7% 22/33 • Number of events 134
Metabolism and nutrition disorders Blood glucose increased	3.0% 1/33 • Number of events 1
Metabolism and nutrition disorders Serum albumin decreased	6.1% 2/33 • Number of events 2
Metabolism and nutrition disorders Serum sodium decreased	3.0% 1/33 • Number of events 1
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	42.4% 14/33 • Number of events 36
Musculoskeletal and connective tissue disorders Osteoporosis	3.0% 1/33 • Number of events 1
Nervous system disorders Headache	6.1% 2/33 • Number of events 3
Nervous system disorders Memory impairment	3.0% 1/33 • Number of events 1
Nervous system disorders Peripheral sensory neuropathy	48.5% 16/33 • Number of events 52
Nervous system disorders Syncope vasovagal	3.0% 1/33 • Number of events 1
Nervous system disorders Tremor	6.1% 2/33 • Number of events 4
Psychiatric disorders Insomnia	6.1% 2/33 • Number of events 3
Renal and urinary disorders Cystitis	12.1% 4/33 • Number of events 9
Reproductive system and breast disorders Gynecomastia	3.0% 1/33 • Number of events 1
Reproductive system and breast disorders Vaginal discharge	3.0% 1/33 • Number of events 1
Respiratory, thoracic and mediastinal disorders Cough	6.1% 2/33 • Number of events 2
Respiratory, thoracic and mediastinal disorders Dyspnea	6.1% 2/33 • Number of events 2
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	6.1% 2/33 • Number of events 2
Respiratory, thoracic and mediastinal disorders Respiratory disorder	3.0% 1/33 • Number of events 1
Skin and subcutaneous tissue disorders Dry skin	3.0% 1/33 • Number of events 1
Skin and subcutaneous tissue disorders Pruritus	6.1% 2/33 • Number of events 2
Skin and subcutaneous tissue disorders Rash desquamating	42.4% 14/33 • Number of events 34
Vascular disorders Hypotension	3.0% 1/33 • Number of events 1
Vascular disorders Thrombosis	6.1% 2/33 • Number of events 2

Additional Information

Craig B. Reeder, MD

Mayo Clinic Arizona

Email: Reeder.Craig@mayo.edu

Results disclosure agreements

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