Trial Outcomes & Findings for R-ICE and Lenalidomide in Treating Patients With First-Relapse/Primary Refractory Diffuse Large B-Cell Lymphoma (NCT NCT02628405)
NCT ID: NCT02628405
Last Updated: 2024-07-01
Results Overview
Will be defined as a complete metabolic response or partial metabolic response. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
Recruitment status
ACTIVE_NOT_RECRUITING
Study phase
PHASE1/PHASE2
Target enrollment
30 participants
Primary outcome timeframe
At 42 days (after 2 courses) of treatment
Results posted on
2024-07-01
Participant Flow
Participant milestones
| Measure |
Treatment (R2-ICE)
Patients receive lenalidomide PO daily on days 1-14, rituximab IV on day 1, ifosfamide IV over 24 hours on day 2, carboplatin IV over 1-2 hours on day 2, and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients achieving CMR, PMR, or NMR may receive 2 more cycles per physician discretion. After completion of 2 cycles of R2ICE treatment, patients achieving objective status of CMR, PMR or NMR may proceed to SCT during the event monitoring phase.\> \> Carboplatin: Given IV\>
\> Etoposide: Given IV\>
\> Ifosfamide: Given IV\>
\> Laboratory Biomarker Analysis: Correlative studies\>
\> Lenalidomide: Given PO\>
\> Rituximab: Given IV
|
|---|---|
|
Overall Study
STARTED
|
30
|
|
Overall Study
COMPLETED
|
30
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
R-ICE and Lenalidomide in Treating Patients With First-Relapse/Primary Refractory Diffuse Large B-Cell Lymphoma
Baseline characteristics by cohort
| Measure |
Treatment (R2-ICE)
n=30 Participants
Patients receive lenalidomide PO daily on days 1-14, rituximab IV on day 1, ifosfamide IV over 24 hours on day 2, carboplatin IV over 1-2 hours on day 2, and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients achieving CMR, PMR, or NMR may receive 2 more cycles per physician discretion. After completion of 2 cycles of R2ICE treatment, patients achieving objective status of CMR, PMR or NMR may proceed to SCT during the event monitoring phase.\> \> Carboplatin: Given IV\>
\> Etoposide: Given IV\>
\> Ifosfamide: Given IV\>
\> Laboratory Biomarker Analysis: Correlative studies\>
\> Lenalidomide: Given PO\>
\> Rituximab: Given IV
|
|---|---|
|
Age, Continuous
|
62.3 years
STANDARD_DEVIATION 9.50 • n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 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
|
0 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
|
0 Participants
n=5 Participants
|
|
ECOG PS
0
|
17 Participants
n=5 Participants
|
|
ECOG PS
1
|
13 Participants
n=5 Participants
|
|
Clinical Stage
1
|
4 Participants
n=5 Participants
|
|
Clinical Stage
2
|
2 Participants
n=5 Participants
|
|
Clinical Stage
3
|
6 Participants
n=5 Participants
|
|
Clinical Stage
4
|
18 Participants
n=5 Participants
|
|
Number of Prior Regimens
1 Prior Regimen
|
27 Participants
n=5 Participants
|
|
Number of Prior Regimens
2 Prior Regimens
|
2 Participants
n=5 Participants
|
|
Number of Prior Regimens
3 Prior Regimens
|
1 Participants
n=5 Participants
|
|
Histology by Central Pathology Review
Diffuse large B-cell lymphoma
|
30 Participants
n=5 Participants
|
|
Histology by Central Pathology Review
Not Diffuse large B-cell lymphoma
|
0 Participants
n=5 Participants
|
|
CD20 by Central Pathology Review
Positive
|
30 Participants
n=5 Participants
|
|
CD20 by Central Pathology Review
Negative
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: At 42 days (after 2 courses) of treatmentWill be defined as a complete metabolic response or partial metabolic response. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
Outcome measures
| Measure |
Treatment (R2-ICE)
n=30 Participants
Patients receive lenalidomide PO daily on days 1-14, rituximab IV on day 1, ifosfamide IV over 24 hours on day 2, carboplatin IV over 1-2 hours on day 2, and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients achieving CMR, PMR, or NMR may receive 2 more cycles per physician discretion. After completion of 2 cycles of R2ICE treatment, patients achieving objective status of CMR, PMR or NMR may proceed to SCT during the event monitoring phase.
\>
\> Carboplatin: Given IV
\>
\> Etoposide: Given IV
\>
\> Ifosfamide: Given IV
\>
\> Laboratory Biomarker Analysis: Correlative studies
\>
\> Lenalidomide: Given PO
\>
\> Rituximab: Given IV
|
|---|---|
|
Overall Response Rate (Phase II)
|
0.567 proportion of participants
Interval 0.374 to 0.745
|
SECONDARY outcome
Timeframe: At 42 days of treatmentEstimated by the number of patients who proceed to transplant divided by \> the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportion will be calculated.
Outcome measures
| Measure |
Treatment (R2-ICE)
n=30 Participants
Patients receive lenalidomide PO daily on days 1-14, rituximab IV on day 1, ifosfamide IV over 24 hours on day 2, carboplatin IV over 1-2 hours on day 2, and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients achieving CMR, PMR, or NMR may receive 2 more cycles per physician discretion. After completion of 2 cycles of R2ICE treatment, patients achieving objective status of CMR, PMR or NMR may proceed to SCT during the event monitoring phase.
\>
\> Carboplatin: Given IV
\>
\> Etoposide: Given IV
\>
\> Ifosfamide: Given IV
\>
\> Laboratory Biomarker Analysis: Correlative studies
\>
\> Lenalidomide: Given PO
\>
\> Rituximab: Given IV
|
|---|---|
|
Proportion of Patients Proceeding to Stem Cell Transplant
|
0.467 proportion of participants
Interval 0.283 to 0.657
|
SECONDARY outcome
Timeframe: Up to 5 yearsEstimated by the number of patients with an objective status of complete metabolic response divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true complete metabolic response rate will be calculated.
Outcome measures
| Measure |
Treatment (R2-ICE)
n=30 Participants
Patients receive lenalidomide PO daily on days 1-14, rituximab IV on day 1, ifosfamide IV over 24 hours on day 2, carboplatin IV over 1-2 hours on day 2, and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients achieving CMR, PMR, or NMR may receive 2 more cycles per physician discretion. After completion of 2 cycles of R2ICE treatment, patients achieving objective status of CMR, PMR or NMR may proceed to SCT during the event monitoring phase.
\>
\> Carboplatin: Given IV
\>
\> Etoposide: Given IV
\>
\> Ifosfamide: Given IV
\>
\> Laboratory Biomarker Analysis: Correlative studies
\>
\> Lenalidomide: Given PO
\>
\> Rituximab: Given IV
|
|---|---|
|
Complete Metabolic Response Rate
|
0.333 proportion of participants
Interval 0.173 to 0.528
|
SECONDARY outcome
Timeframe: From registration to death due to any cause, assessed up to 5 yearsThe percentage of participants alive will be estimated using the method of Kaplan-Meier.
Outcome measures
| Measure |
Treatment (R2-ICE)
n=30 Participants
Patients receive lenalidomide PO daily on days 1-14, rituximab IV on day 1, ifosfamide IV over 24 hours on day 2, carboplatin IV over 1-2 hours on day 2, and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients achieving CMR, PMR, or NMR may receive 2 more cycles per physician discretion. After completion of 2 cycles of R2ICE treatment, patients achieving objective status of CMR, PMR or NMR may proceed to SCT during the event monitoring phase.
\>
\> Carboplatin: Given IV
\>
\> Etoposide: Given IV
\>
\> Ifosfamide: Given IV
\>
\> Laboratory Biomarker Analysis: Correlative studies
\>
\> Lenalidomide: Given PO
\>
\> Rituximab: Given IV
|
|---|---|
|
Overall Survival
|
NA percentage of participants
Interval 14.4 to
Not enough events of death.
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 5 yearsEvaluated by 2 methods: Hans algorithm by immunohistochemistry and gene expression profiling using nanostring technology. For each method, the relationship between overall response (responder versus non-responder) complete response rate and subtype will be evaluated using Chi-square tests (or Fisher's exact test if the data in the contingency table is sparse).
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 5 yearsEvaluated by calculating the percentage (%) standardized uptake value noted on interim positron emission tomography/computed tomography scan and correlated with the overall response (responder versus non-responder) by using a two sample t-test.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 5 yearsEvaluated by calculating the percentage (%) anatomic size reduction noted on interim positron emission tomography/computed tomography scan and correlated with the overall response (responder versus non-responder) by using a two sample t-test.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 5 yearsThe correlation of minimal residual disease detection (positive versus negative) with overall response will be evaluated using Chi-square tests (or Fisher's exact test if the data in the contingency table is sparse).
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 5 yearsThe correlation of minimal residual disease quantification (responder versus non-responder) with overall response will be evaluated using two sample t-tests.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 5 yearsSome of the initial work for which this would be utilized would include but not limited to studying the serum free light chains, serum free deoxyribonucleic acid and the minimal residual disease. These measures will be summarized descriptively using medians and ranges (continuous measures) or frequencies (categorical measures).
Outcome measures
Outcome data not reported
Adverse Events
Treatment (R2-ICE)
Serious events: 16 serious events
Other events: 30 other events
Deaths: 12 deaths
Serious adverse events
| Measure |
Treatment (R2-ICE)
n=30 participants at risk
Rituximab: Given IV
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
10.0%
3/30 • Number of events 3 • Up to 5 years
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
23.3%
7/30 • Number of events 7 • Up to 5 years
|
|
Cardiac disorders
Atrial fibrillation
|
6.7%
2/30 • Number of events 2 • Up to 5 years
|
|
Cardiac disorders
Cardiac disorders - Other, specify
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Gastrointestinal disorders
Abdominal pain
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Gastrointestinal disorders
Nausea
|
6.7%
2/30 • Number of events 2 • Up to 5 years
|
|
Gastrointestinal disorders
Vomiting
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
General disorders
Death NOS
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Infections and infestations
Lung infection
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Infections and infestations
Soft tissue infection
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Infections and infestations
Upper respiratory infection
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Investigations
Lymphocyte count decreased
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Investigations
Neutrophil count decreased
|
10.0%
3/30 • Number of events 4 • Up to 5 years
|
|
Investigations
Platelet count decreased
|
13.3%
4/30 • Number of events 6 • Up to 5 years
|
|
Investigations
White blood cell decreased
|
6.7%
2/30 • Number of events 2 • Up to 5 years
|
|
Metabolism and nutrition disorders
Dehydration
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hypokalemia
|
6.7%
2/30 • Number of events 3 • Up to 5 years
|
|
Nervous system disorders
Encephalopathy
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Nervous system disorders
Syncope
|
6.7%
2/30 • Number of events 2 • Up to 5 years
|
|
Renal and urinary disorders
Acute kidney injury
|
6.7%
2/30 • Number of events 2 • Up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Vascular disorders
Thromboembolic event
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
Other adverse events
| Measure |
Treatment (R2-ICE)
n=30 participants at risk
Rituximab: Given IV
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
43.3%
13/30 • Number of events 25 • Up to 5 years
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
3.3%
1/30 • Number of events 2 • Up to 5 years
|
|
Ear and labyrinth disorders
Tinnitus
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Eye disorders
Blurred vision
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Gastrointestinal disorders
Abdominal pain
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Gastrointestinal disorders
Constipation
|
10.0%
3/30 • Number of events 7 • Up to 5 years
|
|
Gastrointestinal disorders
Diarrhea
|
6.7%
2/30 • Number of events 2 • Up to 5 years
|
|
Gastrointestinal disorders
Dyspepsia
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Gastrointestinal disorders
Mucositis oral
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Gastrointestinal disorders
Nausea
|
13.3%
4/30 • Number of events 6 • Up to 5 years
|
|
General disorders
Chills
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
General disorders
Fatigue
|
26.7%
8/30 • Number of events 9 • Up to 5 years
|
|
General disorders
Pain
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Infections and infestations
Sepsis
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Infections and infestations
Upper respiratory infection
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Investigations
Alanine aminotransferase increased
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Investigations
CD4 lymphocytes decreased
|
3.3%
1/30 • Number of events 2 • Up to 5 years
|
|
Investigations
Creatinine increased
|
6.7%
2/30 • Number of events 3 • Up to 5 years
|
|
Investigations
Lymphocyte count decreased
|
33.3%
10/30 • Number of events 20 • Up to 5 years
|
|
Investigations
Neutrophil count decreased
|
80.0%
24/30 • Number of events 50 • Up to 5 years
|
|
Investigations
Platelet count decreased
|
93.3%
28/30 • Number of events 61 • Up to 5 years
|
|
Investigations
Weight loss
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Investigations
White blood cell decreased
|
80.0%
24/30 • Number of events 57 • Up to 5 years
|
|
Metabolism and nutrition disorders
Acidosis
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Metabolism and nutrition disorders
Anorexia
|
10.0%
3/30 • Number of events 3 • Up to 5 years
|
|
Metabolism and nutrition disorders
Dehydration
|
10.0%
3/30 • Number of events 3 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
6.7%
2/30 • Number of events 2 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hypokalemia
|
13.3%
4/30 • Number of events 4 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
6.7%
2/30 • Number of events 2 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hyponatremia
|
3.3%
1/30 • Number of events 2 • Up to 5 years
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
6.7%
2/30 • Number of events 2 • Up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
10.0%
3/30 • Number of events 4 • Up to 5 years
|
|
Nervous system disorders
Dizziness
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Nervous system disorders
Dysgeusia
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Nervous system disorders
Headache
|
10.0%
3/30 • Number of events 3 • Up to 5 years
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Nervous system disorders
Presyncope
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Nervous system disorders
Syncope
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Psychiatric disorders
Anxiety
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Psychiatric disorders
Confusion
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Psychiatric disorders
Insomnia
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Renal and urinary disorders
Acute kidney injury
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
23.3%
7/30 • Number of events 15 • Up to 5 years
|
|
Skin and subcutaneous tissue disorders
Photosensitivity
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
20.0%
6/30 • Number of events 10 • Up to 5 years
|
|
Vascular disorders
Flushing
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Vascular disorders
Hypotension
|
3.3%
1/30 • Number of events 1 • Up to 5 years
|
|
Vascular disorders
Thromboembolic event
|
16.7%
5/30 • Number of events 11 • Up to 5 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place