Trial Outcomes & Findings for Treatment of Chronic Lymphocytic Leukemia in Patients Previously Exposed to Rituximab (NCT NCT01123356)

Last Updated: 2015-12-03

Results Overview

Obtain early assessment of the efficacy of the intracycle sequential administration of ofatumumab and lenalidomide in the treatment of chronic lymphocytic leukemia (CLL) after prior use of rituximab. Response was categorized according to the IW-CLL criteria which includes the following: Complete remission (CR), CR with incomplete marrow recovery (CRi)Partial remission (PR), Progressive disease (PD), Stable disease (SD). Overall response rate was defined as those who experienced a response of CR, CRi or PR.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

21 participants

Primary outcome timeframe

30 Weeks

Results posted on

2015-12-03

Participant Flow

Participant milestones

Participant milestones
Measure	Oratumumab and Lenalidomide Single arm, non randomized study Ofatumumab, Lenalidomide: -Ofatumumab 2000 mg (300 mg on first cycle) IV on day 1. * Lenalidomide 10 mg (5 mg on first cycle) PO days 8-28. * Treatment to be administered for up to 6 cycles
Overall Study STARTED	21
Overall Study COMPLETED	14
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Oratumumab and Lenalidomide Single arm, non randomized study Ofatumumab, Lenalidomide: -Ofatumumab 2000 mg (300 mg on first cycle) IV on day 1. * Lenalidomide 10 mg (5 mg on first cycle) PO days 8-28. * Treatment to be administered for up to 6 cycles
Overall Study Adverse Event	2
Overall Study Lack of Efficacy	4
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Treatment of Chronic Lymphocytic Leukemia in Patients Previously Exposed to Rituximab

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Oratumumab and Lenalidomide n=21 Participants Single arm, non randomized study Ofatumumab, Lenalidomide: -Ofatumumab 2000 mg (300 mg on first cycle) IV on day 1. * Lenalidomide 10 mg (5 mg on first cycle) PO days 8-28. * Treatment to be administered for up to 6 cycles
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=5 Participants
Age, Categorical >=65 years	10 Participants n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 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	4 Participants n=5 Participants
Race (NIH/OMB) White	17 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

PRIMARY outcome

Timeframe: 30 Weeks

Population: Overall response rate is defined as response (CR, CRi or PR) at cycle 3 or cycle 6 evaluation. Only patients who completed at least 3 cycles were eligible for analysis for this outcome measure.

Outcome measures

Outcome measures
Measure	Oratumumab and Lenalidomide n=19 Participants Single arm, non randomized study Ofatumumab, Lenalidomide: -Ofatumumab 2000 mg (300 mg on first cycle) IV on day 1. * Lenalidomide 10 mg (5 mg on first cycle) PO days 8-28. * Treatment to be administered for up to 6 cycles
Overall Response Rate	53 percentage of participants Interval 32.0 to 73.0

SECONDARY outcome

Timeframe: 30 weeks

Population: Adverse Events were assessed at each treatment visit. All patients who were treated are included in the adverse event analysis.

Frequency of adverse and severe adverse events

Outcome measures

Outcome measures
Measure	Oratumumab and Lenalidomide n=21 Participants Single arm, non randomized study Ofatumumab, Lenalidomide: -Ofatumumab 2000 mg (300 mg on first cycle) IV on day 1. * Lenalidomide 10 mg (5 mg on first cycle) PO days 8-28. * Treatment to be administered for up to 6 cycles
Frequency of Adverse and Severe Adverse Events Number of SAEs	4 participants
Frequency of Adverse and Severe Adverse Events Neutropenia	19 participants
Frequency of Adverse and Severe Adverse Events grade 3/4 neutropenia	10 participants
Frequency of Adverse and Severe Adverse Events thrombocytopenia	15 participants
Frequency of Adverse and Severe Adverse Events grade 3/4 thrombocytopenia	4 participants
Frequency of Adverse and Severe Adverse Events tumor flare reaction	9 participants
Frequency of Adverse and Severe Adverse Events grade 3 tumor flare reaction	1 participants

SECONDARY outcome

Timeframe: 30 Weeks

Population: The biomarker sub-study was not completed due to poor accrual to this substudy and lack of feasibility.

Biomarkers changes during treatment. A minimum of 5 subjects will be enrolled in the biomarkers sub-study. Only those subjects enrolled at MUSC will be considered for the biomarkers sub-study. At day 1 of cycle 1, day 8 of cycle 1, day 1 of cycle 2 and day 8 of cycles 2, blood samples will be obtained for assessment of biomarkers.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 30 weeks

Population: Adverse Events were assessed at each treatment visit. All patients who were treated are included in the adverse event analysis.

Number of adverse events occuring in greater than 20% of subjects

Outcome measures

Outcome measures
Measure	Oratumumab and Lenalidomide n=21 Participants Single arm, non randomized study Ofatumumab, Lenalidomide: -Ofatumumab 2000 mg (300 mg on first cycle) IV on day 1. * Lenalidomide 10 mg (5 mg on first cycle) PO days 8-28. * Treatment to be administered for up to 6 cycles
Frequency of Adverse Events	15 events

SECONDARY outcome

Timeframe: 30 weeks

Population: Adverse Events were assessed at each treatment visit. All patients who were treated are included in the adverse event analysis.

Number of dose reductions due to toxicity.

Outcome measures

Outcome measures
Measure	Oratumumab and Lenalidomide n=21 Participants Single arm, non randomized study Ofatumumab, Lenalidomide: -Ofatumumab 2000 mg (300 mg on first cycle) IV on day 1. * Lenalidomide 10 mg (5 mg on first cycle) PO days 8-28. * Treatment to be administered for up to 6 cycles
Dose Reductions Due to Adverse Events.	17 dose reductions

Adverse Events

Oratumumab and Lenalidomide

Serious events: 4 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Oratumumab and Lenalidomide n=21 participants at risk Single arm, non randomized study Ofatumumab, Lenalidomide: -Ofatumumab 2000 mg (300 mg on first cycle) IV on day 1. * Lenalidomide 10 mg (5 mg on first cycle) PO days 8-28. * Treatment to be administered for up to 6 cycles
Investigations ALT Increase	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Blood and lymphatic system disorders Febrile Neutropenia	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Respiratory, thoracic and mediastinal disorders Pulmonary Edema	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Vascular disorders Thromboembolic Event	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.

Other adverse events

Other adverse events
Measure	Oratumumab and Lenalidomide n=21 participants at risk Single arm, non randomized study Ofatumumab, Lenalidomide: -Ofatumumab 2000 mg (300 mg on first cycle) IV on day 1. * Lenalidomide 10 mg (5 mg on first cycle) PO days 8-28. * Treatment to be administered for up to 6 cycles
Investigations Neutrophil count decreased	90.5% 19/21 All subjects enrolled on study were evaluated for toxicity.
Investigations Platelet count decreased	71.4% 15/21 All subjects enrolled on study were evaluated for toxicity.
General disorders fatigue	52.4% 11/21 All subjects enrolled on study were evaluated for toxicity.
General disorders Tumor flare reaction	42.9% 9/21 All subjects enrolled on study were evaluated for toxicity.
Respiratory, thoracic and mediastinal disorders Dyspnea	38.1% 8/21 All subjects enrolled on study were evaluated for toxicity.
Metabolism and nutrition disorders hypernatremia	38.1% 8/21 All subjects enrolled on study were evaluated for toxicity.
General disorders Infusion related reaction	33.3% 7/21 All subjects enrolled on study were evaluated for toxicity.
Nervous system disorders dizziness	33.3% 7/21 All subjects enrolled on study were evaluated for toxicity.
Metabolism and nutrition disorders hyperglycemia	33.3% 7/21 All subjects enrolled on study were evaluated for toxicity.
Cardiac disorders Tachycardia	33.3% 7/21 All subjects enrolled on study were evaluated for toxicity.
Investigations Aspartate aminotransferase increased	33.3% 7/21 All subjects enrolled on study were evaluated for toxicity.
Investigations creatinine increased	42.9% 9/21 All subjects enrolled on study were evaluated for toxicity.
Respiratory, thoracic and mediastinal disorders cough	28.6% 6/21 All subjects enrolled on study were evaluated for toxicity.
Metabolism and nutrition disorders hypoalbuminemia	33.3% 7/21 All subjects enrolled on study were evaluated for toxicity.
Investigations lactic dehydrogenase increased	28.6% 6/21 All subjects enrolled on study were evaluated for toxicity.
Blood and lymphatic system disorders Anemia	66.7% 14/21 All subjects enrolled on study were evaluated for toxicity.
General disorders Night Sweats	23.8% 5/21 All subjects enrolled on study were evaluated for toxicity.
Metabolism and nutrition disorders hypocalcemia	23.8% 5/21 All subjects enrolled on study were evaluated for toxicity.
Psychiatric disorders insomnia	19.0% 4/21 All subjects enrolled on study were evaluated for toxicity.
Gastrointestinal disorders nausea	19.0% 4/21 All subjects enrolled on study were evaluated for toxicity.
General disorders fever	19.0% 4/21 All subjects enrolled on study were evaluated for toxicity.
Investigations Alanine amniotransferase increased	14.3% 3/21 All subjects enrolled on study were evaluated for toxicity.
Metabolism and nutrition disorders Hyperkalemia	19.0% 4/21 All subjects enrolled on study were evaluated for toxicity.
General disorders pallor	14.3% 3/21 All subjects enrolled on study were evaluated for toxicity.
Metabolism and nutrition disorders hypophosphatemia	14.3% 3/21 All subjects enrolled on study were evaluated for toxicity.
Gastrointestinal disorders constipation	14.3% 3/21 All subjects enrolled on study were evaluated for toxicity.
Gastrointestinal disorders Abdominal discomfort	14.3% 3/21 All subjects enrolled on study were evaluated for toxicity.
Musculoskeletal and connective tissue disorders leg cramps	19.0% 4/21 All subjects enrolled on study were evaluated for toxicity.
Gastrointestinal disorders diarrhea	14.3% 3/21 All subjects enrolled on study were evaluated for toxicity.
Investigations Blood bilirubin increased	14.3% 3/21 All subjects enrolled on study were evaluated for toxicity.
Investigations hyperphosphatemia	19.0% 4/21 All subjects enrolled on study were evaluated for toxicity.
Investigations hypermagnesemia	14.3% 3/21 All subjects enrolled on study were evaluated for toxicity.
Metabolism and nutrition disorders hyperuricemia	23.8% 5/21 All subjects enrolled on study were evaluated for toxicity.
Vascular disorders hypotension	14.3% 3/21 All subjects enrolled on study were evaluated for toxicity.
Musculoskeletal and connective tissue disorders weakness	14.3% 3/21 All subjects enrolled on study were evaluated for toxicity.
Investigations alkaline phosphatase increased	23.8% 5/21 All subjects enrolled on study were evaluated for toxicity.
Respiratory, thoracic and mediastinal disorders allergic rhinitis	9.5% 2/21 All subjects enrolled on study were evaluated for toxicity.
Respiratory, thoracic and mediastinal disorders bronchitis	9.5% 2/21 All subjects enrolled on study were evaluated for toxicity.
General disorders chills	9.5% 2/21 All subjects enrolled on study were evaluated for toxicity.
Metabolism and nutrition disorders hypokalemia	9.5% 2/21 All subjects enrolled on study were evaluated for toxicity.
Cardiac disorders Bradycardia	9.5% 2/21 All subjects enrolled on study were evaluated for toxicity.
Metabolism and nutrition disorders anorexia	14.3% 3/21 All subjects enrolled on study were evaluated for toxicity.
Renal and urinary disorders acute renal failure	9.5% 2/21 All subjects enrolled on study were evaluated for toxicity.
Metabolism and nutrition disorders hypomagnesemia	9.5% 2/21 All subjects enrolled on study were evaluated for toxicity.
Respiratory, thoracic and mediastinal disorders wheezing	9.5% 2/21 All subjects enrolled on study were evaluated for toxicity.
Metabolism and nutrition disorders chloride increased	14.3% 3/21 All subjects enrolled on study were evaluated for toxicity.
Investigations CO2 content decreased	14.3% 3/21 All subjects enrolled on study were evaluated for toxicity.
Gastrointestinal disorders abdominal pain	9.5% 2/21 All subjects enrolled on study were evaluated for toxicity.
General disorders non-cardiac chest pain	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Skin and subcutaneous tissue disorders actinic keratosis	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Vascular disorders hypertension	19.0% 4/21 All subjects enrolled on study were evaluated for toxicity.
Vascular disorders hot flashes	9.5% 2/21 All subjects enrolled on study were evaluated for toxicity.
Musculoskeletal and connective tissue disorders back pain	14.3% 3/21 All subjects enrolled on study were evaluated for toxicity.
Investigations uric acid decreased	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Investigations hypogammaglobulinemia	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Musculoskeletal and connective tissue disorders pain in extremity	14.3% 3/21 All subjects enrolled on study were evaluated for toxicity.
Nervous system disorders dysgeusia	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
General disorders edema face	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Skin and subcutaneous tissue disorders skin hyperpigmentation	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Skin and subcutaneous tissue disorders pruritis	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Cardiac disorders irregular heartbeat	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Infections and infestations lymphadenopathy	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Musculoskeletal and connective tissue disorders neck pain	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Immune system disorders lymph node pain	19.0% 4/21 All subjects enrolled on study were evaluated for toxicity.
Respiratory, thoracic and mediastinal disorders upper respiratory infection	9.5% 2/21 All subjects enrolled on study were evaluated for toxicity.
Gastrointestinal disorders vomiting	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Investigations white blood cell decreased	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Respiratory, thoracic and mediastinal disorders pleuritic pain	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Investigations weight loss	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Skin and subcutaneous tissue disorders alopecia	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Injury, poisoning and procedural complications bruising	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Eye disorders dry eye	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Vascular disorders flushing	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Eye disorders itchy eye	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Vascular disorders pulmonari emboli	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Renal and urinary disorders renal insufficiency	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Eye disorders watering eyes	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Psychiatric disorders agitation	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Musculoskeletal and connective tissue disorders muscle cramping	9.5% 2/21 All subjects enrolled on study were evaluated for toxicity.
Gastrointestinal disorders espophagitis	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Respiratory, thoracic and mediastinal disorders hypoxia	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
General disorders Edema limbs	9.5% 2/21 All subjects enrolled on study were evaluated for toxicity.
Cardiac disorders sinus tachycardia	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Infections and infestations pneumonia	14.3% 3/21 All subjects enrolled on study were evaluated for toxicity.
Respiratory, thoracic and mediastinal disorders pleural effusion	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Respiratory, thoracic and mediastinal disorders sore throat	9.5% 2/21 All subjects enrolled on study were evaluated for toxicity.
Skin and subcutaneous tissue disorders dry skin	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Investigations chloride decreased	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Investigations blood protein decreased	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Ear and labyrinth disorders Meniere's disease	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Skin and subcutaneous tissue disorders sunburn	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
General disorders sweating	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
General disorders swollen feeling	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Infections and infestations cellulitis	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Respiratory, thoracic and mediastinal disorders nasal congestion	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Psychiatric disorders mood swings	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Skin and subcutaneous tissue disorders rash maculopapular	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Skin and subcutaneous tissue disorders rash (NOS)	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Metabolism and nutrition disorders dehydration	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Metabolism and nutrition disorders hypercalcemia	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Nervous system disorders paresthesia	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.
Gastrointestinal disorders heartburn	4.8% 1/21 All subjects enrolled on study were evaluated for toxicity.

Additional Information

Clinical Trials Network Manager

Medical University of South Carolina

Phone: 843-792-1753

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place