Treatment of Chronic Lymphocytic Leukemia in Patients Previously Exposed to Rituximab

• Sponsor: Medical University of South Carolina (Other)
• Overall Status: Completed
• CT.gov ID: NCT01123356
• Collaborator: GlaxoSmithKline (Industry), Celgene Corporation (Industry)
• Enrollment: 21
• Locations: 2
• Arm: 1
• Duration (Months): 37
• Patients Per Site: 10.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia	Drug: Ofatumumab; Drug: Lenalidomide	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Trial of Intracycle Sequential Ofatumumab and Lenalidomide for the Treatment of Chronic Lymphocytic Leukemia in Patients Previously Exposed to Rituximab
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Drug: Ofatumumab; 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; Other Names: Arzerra ; Drug: Lenalidomide; -Lenalidomide 10 mg (5 mg on first cycle) PO days 8-28 for up to 6 cycles (28 day cycles); Other Names: Revlimid

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Frequency of Adverse and Severe Adverse Events [30 weeks]

   Frequency of adverse and severe adverse events

2. 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.

3. Frequency of Adverse Events [30 weeks]

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

4. Dose Reductions Due to Adverse Events. [30 weeks]

   Number of dose reductions due to toxicity.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical University of South Carolina	Charleston	South Carolina	United States	29425
2	Greenville Hospital System	Greenville	South Carolina	United States	29605

Sponsors and Collaborators

• Medical University of South Carolina
• GlaxoSmithKline
• Celgene Corporation

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT01123356
• Other Study ID Numbers: 101376 OFT113297
• First Posted: May 14, 2010
• Last Update Posted: Dec 3, 2015
• Last Verified: Jul 1, 2012

• Keywords provided by Medical University of South Carolina: Relapsed chronic lymphocytic leukemia
• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Lenalidomide; Ofatumumab

Study Results

Participant Flow

Arm/Group Title	Oratumumab and Lenalidomide
Arm/Group Description	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
Period Title: Overall Study
STARTED	21
COMPLETED	14
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	Oratumumab and Lenalidomide
Arm/Group Description	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 Participants	21
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	11 52.4%
>=65 years	10 47.6%
Sex: Female, Male (Count of Participants)
Female	4 19%
Male	17 81%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 19%
Not Hispanic or Latino	17 81%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 19%
White	17 81%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Oratumumab and Lenalidomide
Arm/Group Description	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
Measure Participants	19
Number (95% Confidence Interval) [percentage of participants]	53 252.4%

2. Secondary Outcome

Title	Frequency of Adverse and Severe Adverse Events
Description	Frequency of adverse and severe adverse events
Time Frame	30 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oratumumab and Lenalidomide
Arm/Group Description	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 Ofatumumab: -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 Lenalidomide: -Lenalidomide 10 mg (5 mg on first cycle) PO days 8-28 for up to 6 cycles (28 day cycles)
Measure Participants	21
Number of SAEs	4 19%
Neutropenia	19 90.5%
grade 3/4 neutropenia	10 47.6%
thrombocytopenia	15 71.4%
grade 3/4 thrombocytopenia	4 19%
tumor flare reaction	9 42.9%
grade 3 tumor flare reaction	1 4.8%

3. Secondary Outcome

Title	Biomarkers Changes During Treatment.
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oratumumab and Lenalidomide
Arm/Group Description	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 Ofatumumab: -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 Lenalidomide: -Lenalidomide 10 mg (5 mg on first cycle) PO days 8-28 for up to 6 cycles (28 day cycles)
Measure Participants	0

4. Secondary Outcome

Title	Frequency of Adverse Events
Description	Number of adverse events occuring in greater than 20% of subjects
Time Frame	30 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oratumumab and Lenalidomide
Arm/Group Description	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 Ofatumumab: -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 Lenalidomide: -Lenalidomide 10 mg (5 mg on first cycle) PO days 8-28 for up to 6 cycles (28 day cycles)
Measure Participants	21
Number [events]	15

5. Secondary Outcome

Title	Dose Reductions Due to Adverse Events.
Description	Number of dose reductions due to toxicity.
Time Frame	30 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oratumumab and Lenalidomide
Arm/Group Description	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 Ofatumumab: -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 Lenalidomide: -Lenalidomide 10 mg (5 mg on first cycle) PO days 8-28 for up to 6 cycles (28 day cycles)
Measure Participants	21
Number [dose reductions]	17

Adverse Events

Adverse Event Reporting Description	All subjects enrolled on study were evaluated for toxicity.
Arm/Group Title	Oratumumab and Lenalidomide
Arm/Group Description	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
All Cause Mortality
	Oratumumab and Lenalidomide
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Oratumumab and Lenalidomide
	Affected / at Risk (%)	# Events
Total	4/21 (19%)
Blood and lymphatic system disorders
Febrile Neutropenia	1/21 (4.8%)
Investigations
ALT Increase	1/21 (4.8%)
Respiratory, thoracic and mediastinal disorders
Pulmonary Edema	1/21 (4.8%)
Vascular disorders
Thromboembolic Event	1/21 (4.8%)
Other (Not Including Serious) Adverse Events
	Oratumumab and Lenalidomide
	Affected / at Risk (%)	# Events
Total	21/21 (100%)
Blood and lymphatic system disorders
Anemia	14/21 (66.7%)
Cardiac disorders
Tachycardia	7/21 (33.3%)
Bradycardia	2/21 (9.5%)
irregular heartbeat	1/21 (4.8%)
sinus tachycardia	1/21 (4.8%)
Ear and labyrinth disorders
Meniere's disease	1/21 (4.8%)
Eye disorders
dry eye	1/21 (4.8%)
itchy eye	1/21 (4.8%)
watering eyes	1/21 (4.8%)
Gastrointestinal disorders
nausea	4/21 (19%)
constipation	3/21 (14.3%)
Abdominal discomfort	3/21 (14.3%)
diarrhea	3/21 (14.3%)
abdominal pain	2/21 (9.5%)
vomiting	1/21 (4.8%)
espophagitis	1/21 (4.8%)
heartburn	1/21 (4.8%)
General disorders
fatigue	11/21 (52.4%)
Tumor flare reaction	9/21 (42.9%)
Infusion related reaction	7/21 (33.3%)
Night Sweats	5/21 (23.8%)
fever	4/21 (19%)
pallor	3/21 (14.3%)
chills	2/21 (9.5%)
non-cardiac chest pain	1/21 (4.8%)
edema face	1/21 (4.8%)
Edema limbs	2/21 (9.5%)
sweating	1/21 (4.8%)
swollen feeling	1/21 (4.8%)
Immune system disorders
lymph node pain	4/21 (19%)
Infections and infestations
lymphadenopathy	1/21 (4.8%)
pneumonia	3/21 (14.3%)
cellulitis	1/21 (4.8%)
Injury, poisoning and procedural complications
bruising	1/21 (4.8%)
Investigations
Neutrophil count decreased	19/21 (90.5%)
Platelet count decreased	15/21 (71.4%)
Aspartate aminotransferase increased	7/21 (33.3%)
creatinine increased	9/21 (42.9%)
lactic dehydrogenase increased	6/21 (28.6%)
Alanine amniotransferase increased	3/21 (14.3%)
Blood bilirubin increased	3/21 (14.3%)
hyperphosphatemia	4/21 (19%)
hypermagnesemia	3/21 (14.3%)
alkaline phosphatase increased	5/21 (23.8%)
CO2 content decreased	3/21 (14.3%)
uric acid decreased	1/21 (4.8%)
hypogammaglobulinemia	1/21 (4.8%)
white blood cell decreased	1/21 (4.8%)
weight loss	1/21 (4.8%)
chloride decreased	1/21 (4.8%)
blood protein decreased	1/21 (4.8%)
Metabolism and nutrition disorders
hypernatremia	8/21 (38.1%)
hyperglycemia	7/21 (33.3%)
hypoalbuminemia	7/21 (33.3%)
hypocalcemia	5/21 (23.8%)
Hyperkalemia	4/21 (19%)
hypophosphatemia	3/21 (14.3%)
hyperuricemia	5/21 (23.8%)
hypokalemia	2/21 (9.5%)
anorexia	3/21 (14.3%)
hypomagnesemia	2/21 (9.5%)
chloride increased	3/21 (14.3%)
dehydration	1/21 (4.8%)
hypercalcemia	1/21 (4.8%)
Musculoskeletal and connective tissue disorders
leg cramps	4/21 (19%)
weakness	3/21 (14.3%)
back pain	3/21 (14.3%)
pain in extremity	3/21 (14.3%)
neck pain	1/21 (4.8%)
muscle cramping	2/21 (9.5%)
Nervous system disorders
dizziness	7/21 (33.3%)
dysgeusia	1/21 (4.8%)
paresthesia	1/21 (4.8%)
Psychiatric disorders
insomnia	4/21 (19%)
agitation	1/21 (4.8%)
mood swings	1/21 (4.8%)
Renal and urinary disorders
acute renal failure	2/21 (9.5%)
renal insufficiency	1/21 (4.8%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	8/21 (38.1%)
cough	6/21 (28.6%)
allergic rhinitis	2/21 (9.5%)
bronchitis	2/21 (9.5%)
wheezing	2/21 (9.5%)
upper respiratory infection	2/21 (9.5%)
pleuritic pain	1/21 (4.8%)
hypoxia	1/21 (4.8%)
pleural effusion	1/21 (4.8%)
sore throat	2/21 (9.5%)
nasal congestion	1/21 (4.8%)
Skin and subcutaneous tissue disorders
actinic keratosis	1/21 (4.8%)
skin hyperpigmentation	1/21 (4.8%)
pruritis	1/21 (4.8%)
alopecia	1/21 (4.8%)
dry skin	1/21 (4.8%)
sunburn	1/21 (4.8%)
rash maculopapular	1/21 (4.8%)
rash (NOS)	1/21 (4.8%)
Vascular disorders
hypotension	3/21 (14.3%)
hypertension	4/21 (19%)
hot flashes	2/21 (9.5%)
flushing	1/21 (4.8%)
pulmonari emboli	1/21 (4.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.