Trial Outcomes & Findings for Rituximab, Pentostatin, Cyclophosphamide, and Lenalidomide in Treating Patients With Previously Untreated B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (NCT NCT00602836)
NCT ID: NCT00602836
Last Updated: 2020-01-27
Results Overview
A complete response, as defined by the National Cancer Institute Working Group (NCIWG), requires all of the following for a period of at least 2 months: \- CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate \& biopsy
COMPLETED
PHASE2
45 participants
12 months
2020-01-27
Participant Flow
Forty-five (45) participants were recruited at Mayo Clinic (Rochester, Florida and Arizona) between March 2009 and December 2009.
One participant was deemed ineligible and is excluded from all analyses per study design.
Participant milestones
| Measure |
PCR-Lenalidomide
Pentostatin, Cyclophosphamide, Rituximab + Lenalidomide
|
|---|---|
|
Overall Study
STARTED
|
44
|
|
Overall Study
COMPLETED
|
39
|
|
Overall Study
NOT COMPLETED
|
5
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Rituximab, Pentostatin, Cyclophosphamide, and Lenalidomide in Treating Patients With Previously Untreated B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Baseline characteristics by cohort
| Measure |
PCR-Lenalidomide
n=44 Participants
Pentostatin, Cyclophosphamide, Rituximab + Lenalidomide
|
|---|---|
|
Age, Continuous
|
65 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
31 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
44 participants
n=5 Participants
|
|
Fluorescence In Situ Hybridization (FISH) Abnormalities
deletion(13q14.2)
|
13 participants
n=5 Participants
|
|
Fluorescence In Situ Hybridization (FISH) Abnormalities
Trisomy 12
|
7 participants
n=5 Participants
|
|
Fluorescence In Situ Hybridization (FISH) Abnormalities
deletion (11q22)
|
6 participants
n=5 Participants
|
|
Fluorescence In Situ Hybridization (FISH) Abnormalities
17p-
|
1 participants
n=5 Participants
|
|
Fluorescence In Situ Hybridization (FISH) Abnormalities
Other
|
2 participants
n=5 Participants
|
|
Fluorescence In Situ Hybridization (FISH) Abnormalities
Normal
|
15 participants
n=5 Participants
|
|
Rai Stage
Stage I-II
|
27 participants
n=5 Participants
|
|
Rai Stage
Stage III-IV
|
17 participants
n=5 Participants
|
|
ZAP-70 Status
Positive (>=20%)
|
24 participants
n=5 Participants
|
|
ZAP-70 Status
Negative (<20%)
|
20 participants
n=5 Participants
|
|
CD38 Status
Positive (>=30%)
|
14 participants
n=5 Participants
|
|
CD38 Status
Negative (<30%)
|
30 participants
n=5 Participants
|
|
Immunoglobulin Variable Heavy Chain (IGVH) Mutation Status
Unmutated
|
22 participants
n=5 Participants
|
|
Immunoglobulin Variable Heavy Chain (IGVH) Mutation Status
Mutated
|
20 participants
n=5 Participants
|
|
Immunoglobulin Variable Heavy Chain (IGVH) Mutation Status
Not tested
|
2 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 monthsA complete response, as defined by the National Cancer Institute Working Group (NCIWG), requires all of the following for a period of at least 2 months: \- CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate \& biopsy
Outcome measures
| Measure |
PCR-Lenalidomide
n=44 Participants
Pentostatin, Cyclophosphamide, Rituximab + Lenalidomide
|
|---|---|
|
Number of Participants With Complete Response (CR)
|
14 participants
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: All patients that began lenalidomide consolidation with either and nPR, PR, or SD were included in this analysis.
According to the NCIWG criteria, response is defined as follows: nPR: Meets all criteria for CR, as described above, except the presence of residual clonal nodules in the bone marrow PR: 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver/spleen size, presence/absence of constitutional symptoms; plus ≥1 of the following: ≥1500/μL polymorphonuclear leukocytes, \>100000/μL platelets, \>11.0 g/dL hemoglobin or 50% improvement for these parameters without transfusions SD: participant who does not meet any of the criteria described above
Outcome measures
| Measure |
PCR-Lenalidomide
n=21 Participants
Pentostatin, Cyclophosphamide, Rituximab + Lenalidomide
|
|---|---|
|
Number of Participants Who Convert From a Nodular Partial Response (nPR), Partial Response (PR), or Stable Disease (SD) After Pentostatin, Cyclophosphamide, and Rituximab (PCR) to a Complete Response (CR) After 6 Courses of Consolidation With Lenalidomide
|
5 Participants
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: All patients that began consolidation with a CR and MRD-negative status were included in this analysis.
MRD refers to small number of leukemic cells that remain in the participant during treatment or after treatment when the participant has achieved CR. For all participants who achieved CR, the follow-up bone marrow sample was tested for malignant B cells to determine if there was any MRD.
Outcome measures
| Measure |
PCR-Lenalidomide
n=5 Participants
Pentostatin, Cyclophosphamide, Rituximab + Lenalidomide
|
|---|---|
|
Number of Participants Who Convert From a CR With Minimal Residual Disease (MRD) Positive Status After PCR to a CR With MRD-negative Status After 6 Courses of Consolidation With Lenalidomide
|
4 Participants
|
SECONDARY outcome
Timeframe: During treatment (up to 5 years)Population: All patients that registered to this trial with the intent-to-treat were included in this analysis.
Response criteria described in above outcomes.
Outcome measures
| Measure |
PCR-Lenalidomide
n=44 Participants
Pentostatin, Cyclophosphamide, Rituximab + Lenalidomide
|
|---|---|
|
Number of Participants With a Response (CR, nPR, PR)
|
38 Participants
|
SECONDARY outcome
Timeframe: time from registration to death (up to 5 years)Population: All patients who registered were included in this analysis.
Overall Survival (OS) was defined as the time from registration to death of any cause. Participants were followed for a maximum of 5 years from registration. The median OS with 95% CI was estimated using the Kaplan Meier method.
Outcome measures
| Measure |
PCR-Lenalidomide
n=44 Participants
Pentostatin, Cyclophosphamide, Rituximab + Lenalidomide
|
|---|---|
|
Overall Survival (OS)
|
NA months
Too few events took place during treatment and follow up to obtain a median value and estimate the 95% CI.
|
SECONDARY outcome
Timeframe: time from registration to progression (up to 5 years)Population: All patients that registered to treatment were included in this analysis.
Treatment Free Survival (TFS) was defined as the time from registration to the earliest date documentation of subsequent treatment or death, whichever came first. Participants were followed for a maximum of 5 years from registration. The median TFS with 95% CI was estimated using the Kaplan Meier method.
Outcome measures
| Measure |
PCR-Lenalidomide
n=44 Participants
Pentostatin, Cyclophosphamide, Rituximab + Lenalidomide
|
|---|---|
|
Treatment Free Survival (TFS)
|
NA months
Interval 48.0 to
Too few events occurred to obtain a median or upper bound of the 95% CI.
|
Adverse Events
PCR-Lenalidomide
Serious adverse events
| Measure |
PCR-Lenalidomide
n=44 participants at risk
Pentostatin, Cyclophosphamide, Rituximab + Lenalidomide
|
|---|---|
|
Cardiac disorders
Atrial flutter
|
2.3%
1/44 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
2.3%
1/44 • Number of events 1
|
|
Infections and infestations
Upper airway infection
|
2.3%
1/44 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
2.3%
1/44 • Number of events 1
|
|
Investigations
Neutrophil count decreased
|
9.1%
4/44 • Number of events 6
|
|
Investigations
Platelet count decreased
|
2.3%
1/44 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
4.5%
2/44 • Number of events 2
|
Other adverse events
| Measure |
PCR-Lenalidomide
n=44 participants at risk
Pentostatin, Cyclophosphamide, Rituximab + Lenalidomide
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
90.9%
40/44 • Number of events 231
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
2.3%
1/44 • Number of events 1
|
|
Cardiac disorders
Atrial fibrillation
|
4.5%
2/44 • Number of events 2
|
|
Cardiac disorders
Atrial flutter
|
2.3%
1/44 • Number of events 1
|
|
Cardiac disorders
Left ventricular failure
|
2.3%
1/44 • Number of events 4
|
|
Cardiac disorders
Restrictive cardiomyopathy
|
2.3%
1/44 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal distension
|
2.3%
1/44 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
2.3%
1/44 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
2.3%
1/44 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhea
|
4.5%
2/44 • Number of events 2
|
|
Gastrointestinal disorders
Flatulence
|
2.3%
1/44 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
13.6%
6/44 • Number of events 11
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
2.3%
1/44 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
9.1%
4/44 • Number of events 8
|
|
General disorders
Chills
|
9.1%
4/44 • Number of events 4
|
|
General disorders
Edema limbs
|
2.3%
1/44 • Number of events 1
|
|
General disorders
Fatigue
|
63.6%
28/44 • Number of events 116
|
|
General disorders
Fever
|
45.5%
20/44 • Number of events 26
|
|
General disorders
Pain-Chest
|
2.3%
1/44 • Number of events 1
|
|
General disorders
Syndromes
|
2.3%
1/44 • Number of events 1
|
|
Hepatobiliary disorders
Gallbladder pain
|
2.3%
1/44 • Number of events 2
|
|
Immune system disorders
Hypersensitivity
|
6.8%
3/44 • Number of events 3
|
|
Infections and infestations
Abdominal infection
|
2.3%
1/44 • Number of events 1
|
|
Infections and infestations
Arthritis infective
|
2.3%
1/44 • Number of events 1
|
|
Infections and infestations
Blood Infection
|
2.3%
1/44 • Number of events 1
|
|
Infections and infestations
Infection without neutropenia
|
4.5%
2/44 • Number of events 2
|
|
Infections and infestations
Lymph gland infection
|
2.3%
1/44 • Number of events 1
|
|
Infections and infestations
Lymphatic infection
|
2.3%
1/44 • Number of events 2
|
|
Infections and infestations
Pneumonia
|
4.5%
2/44 • Number of events 2
|
|
Infections and infestations
Respiratory tract infection
|
9.1%
4/44 • Number of events 4
|
|
Infections and infestations
Sinus infection
|
2.3%
1/44 • Number of events 1
|
|
Infections and infestations
Sinusitis
|
4.5%
2/44 • Number of events 2
|
|
Infections and infestations
Skin (cellulites) infection
|
2.3%
1/44 • Number of events 1
|
|
Infections and infestations
Upper airway infection
|
4.5%
2/44 • Number of events 2
|
|
Infections and infestations
Urinary tract infection
|
2.3%
1/44 • Number of events 1
|
|
Investigations
Aspartate aminotransferase increased
|
2.3%
1/44 • Number of events 1
|
|
Investigations
Bilirubin
|
2.3%
1/44 • Number of events 1
|
|
Investigations
Leukopenia
|
77.3%
34/44 • Number of events 227
|
|
Investigations
Neutrophil count decreased
|
86.4%
38/44 • Number of events 231
|
|
Investigations
Platelet count decreased
|
72.7%
32/44 • Number of events 262
|
|
Metabolism and nutrition disorders
Anorexia
|
9.1%
4/44 • Number of events 6
|
|
Metabolism and nutrition disorders
Dehydration
|
2.3%
1/44 • Number of events 3
|
|
Metabolism and nutrition disorders
Hyponatremia
|
4.5%
2/44 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
2.3%
1/44 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
2.3%
1/44 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
9.1%
4/44 • Number of events 4
|
|
Nervous system disorders
Headache
|
2.3%
1/44 • Number of events 1
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
2.3%
1/44 • Number of events 1
|
|
Psychiatric disorders
Insomnia
|
2.3%
1/44 • Number of events 1
|
|
Renal and urinary disorders
Urinary frequency
|
2.3%
1/44 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
2.3%
1/44 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
9.1%
4/44 • Number of events 9
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
2.3%
1/44 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
2.3%
1/44 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
|
2.3%
1/44 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Photosensitivity
|
2.3%
1/44 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
4.5%
2/44 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Rash
|
56.8%
25/44 • Number of events 48
|
|
Skin and subcutaneous tissue disorders
Sweating
|
4.5%
2/44 • Number of events 2
|
|
Vascular disorders
Flushing
|
2.3%
1/44 • Number of events 1
|
|
Vascular disorders
Hot flashes
|
2.3%
1/44 • Number of events 1
|
|
Vascular disorders
Hypertension
|
4.5%
2/44 • Number of events 3
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place