Chronic Lymphocytic Leukemia
Conditions
Keywords
Relapsed chronic lymphocytic leukemia
Brief summary
The purpose of this research is to evaluate the safety and effectiveness of the drugs lenalidomide and ofatumumab in the treatment of chronic lymphocytic leukemia (CLL).
Interventions
DRUGOfatumumab
* Ofatumumab 2000 mg (300 mg on first cycle) IV on day 1 for up to 6 cycles (28 day cycles) * Treatment to be administered for up to 6 cycles
DRUGLenalidomide
-Lenalidomide 10 mg (5 mg on first cycle) PO days 8-28 for up to 6 cycles (28 day cycles)
Sponsors
GlaxoSmithKline
Celgene Corporation
Medical University of South Carolina
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects must have confirmed diagnosis of chronic lymphocytic leukemia (CLL). 2. Prior therapy with at least one regimen containing rituximab 3. Age \> 18 years. 4. Life expectancy greater than 12 months. 5. ECOG performance status \<2 6. Patients must have normal organ function as defined in the protocol. 7. Patients must have adequate bone marrow function as defined in the protocol. 8. Ability to understand and the willingness to sign a written informed consent document. 9. All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®. 10. Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours prior to prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. 11. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin.
Exclusion criteria
1. Patients who have had chemotherapy or radiotherapy within 4 weeks or received any monoclonal antibody within 6 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. 2. Patients may not be receiving any other investigational agents or other anti-cancer agents or treatments. 3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to ofatumumab or lenalidomide. 4. Uncontrolled concomitant illness. 5. Pregnant women are excluded from this study because lenalidomide is believed to be teratogenic. 6. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with ofatumumab or lenalidomide. 7. Prior treatment with lenalidomide 8. Evidence of laboratory TLS by Cairo-Bishop Definition of Tumor Lysis Syndrome. Subjects may be enrolled upon correction of electrolyte abnormalities. 9. All patients will undergo screening for hepatitis B and may or may not be eligible based on the results as outlined in the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | 30 Weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Adverse and Severe Adverse Events | 30 weeks | Frequency of adverse and severe adverse events |
| Biomarkers Changes During Treatment. | 30 Weeks | 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. |
| Frequency of Adverse Events | 30 weeks | Number of adverse events occuring in greater than 20% of subjects |
| Dose Reductions Due to Adverse Events. | 30 weeks | Number of dose reductions due to toxicity. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Lack of Efficacy | 4 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Oratumumab and Lenalidomide |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 17 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 21 / 21 |
| serious Total, serious adverse events | 4 / 21 |
Outcome results
Primary
Overall Response Rate
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oratumumab and Lenalidomide | Overall Response Rate | 53 percentage of participants |
Secondary
Biomarkers Changes During Treatment.
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.
Time frame: 30 Weeks
Population: The biomarker sub-study was not completed due to poor accrual to this substudy and lack of feasibility.
Secondary
Dose Reductions Due to Adverse Events.
Number of dose reductions due to toxicity.
Time frame: 30 weeks
Population: Adverse Events were assessed at each treatment visit. All patients who were treated are included in the adverse event analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oratumumab and Lenalidomide | Dose Reductions Due to Adverse Events. | 17 dose reductions |
Secondary
Frequency of Adverse and Severe Adverse Events
Frequency of adverse and severe adverse events
Time frame: 30 weeks
Population: Adverse Events were assessed at each treatment visit. All patients who were treated are included in the adverse event analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oratumumab and Lenalidomide | Frequency of Adverse and Severe Adverse Events | Number of SAEs | 4 participants |
| Oratumumab and Lenalidomide | Frequency of Adverse and Severe Adverse Events | Neutropenia | 19 participants |
| Oratumumab and Lenalidomide | Frequency of Adverse and Severe Adverse Events | grade 3/4 neutropenia | 10 participants |
| Oratumumab and Lenalidomide | Frequency of Adverse and Severe Adverse Events | thrombocytopenia | 15 participants |
| Oratumumab and Lenalidomide | Frequency of Adverse and Severe Adverse Events | grade 3/4 thrombocytopenia | 4 participants |
| Oratumumab and Lenalidomide | Frequency of Adverse and Severe Adverse Events | tumor flare reaction | 9 participants |
| Oratumumab and Lenalidomide | Frequency of Adverse and Severe Adverse Events | grade 3 tumor flare reaction | 1 participants |
Secondary
Frequency of Adverse Events
Number of adverse events occuring in greater than 20% of subjects
Time frame: 30 weeks
Population: Adverse Events were assessed at each treatment visit. All patients who were treated are included in the adverse event analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oratumumab and Lenalidomide | Frequency of Adverse Events | 15 events |