Trial Outcomes & Findings for Study of Lenalidomide and Ofatumumab for the Treatment of Relapsed or Refractory Non-Hodgkin's Lymphoma (NCT NCT01060384)
NCT ID: NCT01060384
Last Updated: 2023-10-04
Results Overview
The maximum tolerated dose (MTD) will be defined as the next lowest dose cohort below where ≥ 2/3 or ≥ 3/6 patients experience dose limiting toxicities in cycle 1.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
46 participants
Primary outcome timeframe
7 months
Results posted on
2023-10-04
Participant Flow
All the patients will receive 8 weekly infusions of Ofatumumab 1000mg. Dose escalation of Lenalidomide planned in three dose cohorts. Dose reduction Cohort (-1) will be added if severe adverse events noted in 2/3 patients. Phase II will evaluate Lenalidomide at maximum tolerated dose (MTD) and Ofatumumab in 36 patients.
Participant milestones
| Measure |
Phase 1: Cohort -1
Cohort -1 received 10 mg Lenalidomide per day on days 1-21 every 28 days.
|
Phase 1: Cohort #1
Cohort 1 received 15 mg Lenalidomide per day on days 1-21 every 28 days.
|
Phase 1: Cohort #2
Cohort 2 received 20 mg Lenalidomide on days 1-21 every 28 days.
|
Phase 1: Cohort #3
Cohort 3 received 25 mg Lenalidomide per day on days 1-21 every 28 days.
|
Phase II: Event Free Survival and Overall Survival
Event free and overall survival probabilities will be computed on all patients receiving the MTD dose, including those patients in the phase I portion of the study.
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
4
|
0
|
0
|
36
|
|
Overall Study
COMPLETED
|
6
|
3
|
0
|
0
|
34
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
0
|
2
|
Reasons for withdrawal
| Measure |
Phase 1: Cohort -1
Cohort -1 received 10 mg Lenalidomide per day on days 1-21 every 28 days.
|
Phase 1: Cohort #1
Cohort 1 received 15 mg Lenalidomide per day on days 1-21 every 28 days.
|
Phase 1: Cohort #2
Cohort 2 received 20 mg Lenalidomide on days 1-21 every 28 days.
|
Phase 1: Cohort #3
Cohort 3 received 25 mg Lenalidomide per day on days 1-21 every 28 days.
|
Phase II: Event Free Survival and Overall Survival
Event free and overall survival probabilities will be computed on all patients receiving the MTD dose, including those patients in the phase I portion of the study.
|
|---|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
0
|
|
Overall Study
Death
|
0
|
0
|
0
|
0
|
1
|
|
Overall Study
Intercurrent illness
|
0
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Study of Lenalidomide and Ofatumumab for the Treatment of Relapsed or Refractory Non-Hodgkin's Lymphoma
Baseline characteristics by cohort
| Measure |
Phase 1/Phase II
n=46 Participants
There will be three planned dose cohorts for the Lenalidomide in the Phase 1 portion of this trial. Three evaluable patients will be enrolled in to each of the dose cohorts with an additional 3 patients to be enrolled in the maximum tolerated dose (MTD). Patients will be enrolled in to Phase II using the MTD for Lenalidomide that was determined in Phase 1.
Dose Cohort -1: 10 mg per day. This cohort will be used only if needed due to dose reduction in Dose cohort +1.
Dose Cohort +1: 15 mg per day. Dose Cohort +2: 20 mg per day. Dose Cohort +3: 25 mg per day.
Phase II: An additional 29 response-evaluable patients will be enrolled into Phase II using the MTD for Lenalidomide that was determined in Phase 1.
All subjects will receive the same dosing schedule for Ofatumumab regardless of which Phase of the trial they are enrolled.
|
|---|---|
|
Age, Continuous
|
63.4 years
n=99 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
33 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
46 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
46 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: 7 monthsPopulation: Ten patients were enrolled in Phase 1. One patient was inevaluable, thus 9 patients are evaluable for outcome. Patients will be evaluable for Dose Limiting Toxicity (DLT) if they receive at least 75% of the planned doses of study drugs or they experience DLT in cycle 1 or and have sufficient followup data to determine whether DLT occurred.
The maximum tolerated dose (MTD) will be defined as the next lowest dose cohort below where ≥ 2/3 or ≥ 3/6 patients experience dose limiting toxicities in cycle 1.
Outcome measures
| Measure |
Phase 1
n=9 Participants
Maximum Tolerated Dose (MTD) of Lenalidomide
|
|---|---|
|
Phase I: Maximum Tolerated Dose (MTD) of Lenalidomide
|
10 milligrams
|
SECONDARY outcome
Timeframe: 2 years from start of treatmentPopulation: Six patients in Phase 1 were treated at the MTD and 34 patients enrolled in Phase II were eligible for evaluation. Data was analyzed for all patients treated at the MTD (n=40).
Event free survival is defined as the time from start of treatment to disease progression or death from any cause. Overall survival (OS) is defined as the time from start of treatment to death from any cause. A response-evaluable subject will be considered anyone who completes at least 2 cycles of therapy with documented response or documented progression of disease after at least one complete cycle of therapy but, prior to 2 complete cycles of therapy. A response-evaluable subject will be considered anyone who completes at least 2 cycles of therapy with documented response or documented progression of disease after at least one complete cycle of therapy but, prior to 2 complete cycles of therapy. A non-evaluable subject will be one who receives less than one complete cycle of therapy (ie. 4 infusions of ofatumumab and 21 days of lenalidomide). A non-evaluable subject will also be one that has no documented response prior to treatment withdrawal.
Outcome measures
| Measure |
Phase 1
n=40 Participants
Maximum Tolerated Dose (MTD) of Lenalidomide
|
|---|---|
|
Phase I and Phase II: Event Free Survival and Overall Survival
Estimated 1 year Event Free Survival
|
38 percent of participants
|
|
Phase I and Phase II: Event Free Survival and Overall Survival
Estimated 1 year Overall Survival
|
53 percent of participants
|
|
Phase I and Phase II: Event Free Survival and Overall Survival
Estimated 2 year Event Free Survival
|
20 percent of participants
|
|
Phase I and Phase II: Event Free Survival and Overall Survival
Estimated 2 year Overall Survival
|
44 percent of participants
|
Adverse Events
Phase I: Cohort -1
Serious events: 4 serious events
Other events: 6 other events
Deaths: 1 deaths
Phase 1: Cohort #1
Serious events: 3 serious events
Other events: 4 other events
Deaths: 1 deaths
Phase 1: Cohort #2
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Phase 1: Cohort #3
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Phase 1 & II: Event Free & Overall Survival
Serious events: 14 serious events
Other events: 18 other events
Deaths: 6 deaths
Serious adverse events
| Measure |
Phase I: Cohort -1
n=6 participants at risk
Lenalidomide: 10 mg per day.
|
Phase 1: Cohort #1
n=4 participants at risk
Lenalidomide: 15mg per day.
|
Phase 1: Cohort #2
Lenalidomide: 20mg per day.
|
Phase 1: Cohort #3
Lenalidomide: 25 mg per day.
|
Phase 1 & II: Event Free & Overall Survival
n=36 participants at risk
Event free \& Overall Survival on Lenalidomide at maximum tolerated dose (MTD).
|
|---|---|---|---|---|---|
|
Infections and infestations
Infections and infestations - Other, specify
|
16.7%
1/6 • Number of events 1 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
2.8%
1/36 • Number of events 1 • 6 years
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/6 • 6 years
|
25.0%
1/4 • Number of events 1 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
0.00%
0/36 • 6 years
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/6 • 6 years
|
25.0%
1/4 • Number of events 1 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
0.00%
0/36 • 6 years
|
|
Injury, poisoning and procedural complications
Injury, poisoning and prcedural complications - Other, specify
|
16.7%
1/6 • Number of events 1 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
0.00%
0/36 • 6 years
|
|
Injury, poisoning and procedural complications
Vascular access complication
|
0.00%
0/6 • 6 years
|
25.0%
1/4 • Number of events 1 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
0.00%
0/36 • 6 years
|
|
Nervous system disorders
Stroke
|
16.7%
1/6 • Number of events 1 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
0.00%
0/36 • 6 years
|
|
General disorders
Fever
|
0.00%
0/6 • 6 years
|
50.0%
2/4 • Number of events 6 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
5.6%
2/36 • Number of events 3 • 6 years
|
|
Investigations
Neutrophil count decreased
|
16.7%
1/6 • Number of events 1 • 6 years
|
50.0%
2/4 • Number of events 2 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
5.6%
2/36 • Number of events 2 • 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and medicastinal disorders - Other, specify
|
0.00%
0/6 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
2.8%
1/36 • Number of events 1 • 6 years
|
|
Hepatobiliary disorders
Cholecystitis
|
16.7%
1/6 • Number of events 1 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
0.00%
0/36 • 6 years
|
|
Nervous system disorders
Ataxia
|
0.00%
0/6 • 6 years
|
25.0%
1/4 • Number of events 1 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
0.00%
0/36 • 6 years
|
|
Psychiatric disorders
confusion
|
16.7%
1/6 • Number of events 2 • 6 years
|
25.0%
1/4 • Number of events 1 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
2.8%
1/36 • Number of events 2 • 6 years
|
|
Nervous system disorders
Nervous system disorders - )ther, specify
|
0.00%
0/6 • 6 years
|
25.0%
1/4 • Number of events 1 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
0.00%
0/36 • 6 years
|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/6 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
2.8%
1/36 • Number of events 1 • 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
0.00%
0/6 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
2.8%
1/36 • Number of events 1 • 6 years
|
|
Metabolism and nutrition disorders
Acidosis
|
0.00%
0/6 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
2.8%
1/36 • Number of events 1 • 6 years
|
|
Infections and infestations
sepsis
|
0.00%
0/6 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
2.8%
1/36 • Number of events 1 • 6 years
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications - Other, specify
|
0.00%
0/6 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
2.8%
1/36 • Number of events 1 • 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/6 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
2.8%
1/36 • Number of events 1 • 6 years
|
|
Cardiac disorders
Chest pain
|
0.00%
0/6 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
2.8%
1/36 • Number of events 1 • 6 years
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/6 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
2.8%
1/36 • Number of events 1 • 6 years
|
|
Cardiac disorders
Atrial flutter
|
0.00%
0/6 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
2.8%
1/36 • Number of events 1 • 6 years
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/6 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
2.8%
1/36 • Number of events 1 • 6 years
|
|
Blood and lymphatic system disorders
Platelet count decreased
|
16.7%
1/6 • Number of events 1 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
2.8%
1/36 • Number of events 1 • 6 years
|
|
Gastrointestinal disorders
Nausea
|
16.7%
1/6 • Number of events 2 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
2.8%
1/36 • Number of events 1 • 6 years
|
|
Reproductive system and breast disorders
Testicular pain
|
16.7%
1/6 • Number of events 1 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
0.00%
0/36 • 6 years
|
|
Cardiac disorders
Cardiac arrest
|
0.00%
0/6 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
2.8%
1/36 • Number of events 1 • 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/6 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
2.8%
1/36 • Number of events 1 • 6 years
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/6 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
2.8%
1/36 • Number of events 2 • 6 years
|
|
Renal and urinary disorders
Renal and urinary disorders - Other, specify
|
0.00%
0/6 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
2.8%
1/36 • Number of events 2 • 6 years
|
|
Cardiac disorders
Aortic valve disease
|
0.00%
0/6 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
2.8%
1/36 • Number of events 1 • 6 years
|
|
General disorders
Weakness
|
0.00%
0/6 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
8.3%
3/36 • Number of events 3 • 6 years
|
|
General disorders
Fatigue
|
0.00%
0/6 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
5.6%
2/36 • Number of events 2 • 6 years
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.00%
0/6 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
2.8%
1/36 • Number of events 1 • 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Respiatory, thoracic and mediastinal disorders - Other, specify
|
0.00%
0/6 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
2.8%
1/36 • Number of events 1 • 6 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify
|
0.00%
0/6 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
2.8%
1/36 • Number of events 2 • 6 years
|
|
Cardiac disorders
Left ventricular systolic dysfunction
|
0.00%
0/6 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
2.8%
1/36 • Number of events 1 • 6 years
|
Other adverse events
| Measure |
Phase I: Cohort -1
n=6 participants at risk
Lenalidomide: 10 mg per day.
|
Phase 1: Cohort #1
n=4 participants at risk
Lenalidomide: 15mg per day.
|
Phase 1: Cohort #2
Lenalidomide: 20mg per day.
|
Phase 1: Cohort #3
Lenalidomide: 25 mg per day.
|
Phase 1 & II: Event Free & Overall Survival
n=36 participants at risk
Event free \& Overall Survival on Lenalidomide at maximum tolerated dose (MTD).
|
|---|---|---|---|---|---|
|
Investigations
Neutrophil count decreased
|
50.0%
3/6 • Number of events 22 • 6 years
|
100.0%
4/4 • Number of events 20 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
44.4%
16/36 • Number of events 45 • 6 years
|
|
Investigations
Platelet count decreased
|
16.7%
1/6 • Number of events 2 • 6 years
|
25.0%
1/4 • Number of events 1 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
5.6%
2/36 • Number of events 2 • 6 years
|
|
Investigations
White blood cell decreased
|
16.7%
1/6 • Number of events 4 • 6 years
|
50.0%
2/4 • Number of events 2 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
0.00%
0/36 • 6 years
|
|
General disorders
Infusion related reaction
|
0.00%
0/6 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
8.3%
3/36 • Number of events 3 • 6 years
|
|
Investigations
Investigations - Other, specify
|
0.00%
0/6 • 6 years
|
0.00%
0/4 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
5.6%
2/36 • Number of events 2 • 6 years
|
|
General disorders
Fatigue
|
16.7%
1/6 • Number of events 1 • 6 years
|
25.0%
1/4 • Number of events 1 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
0.00%
0/36 • 6 years
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.00%
0/6 • 6 years
|
25.0%
1/4 • Number of events 1 • 6 years
|
—
0/0 • 6 years
|
—
0/0 • 6 years
|
0.00%
0/36 • 6 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place