Lenalidomide and Ofatumumab in Treating Participants With Previously Treated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01002755
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 36
• Location: 1
• Arm: 1
• Actual Duration (Months): 96.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This phase II trial studies how well lenalidomide and ofatumumab work in treating participants with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma. Drugs used in chemotherapy, such as lenalidomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as ofatumumab, may interfere with the ability of tumor cells to grow and spread. Giving lenalidomide and ofatumumab may work better in treating participants with chronic lymphocytic leukemia or small lymphocytic lymphoma

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia; Fatigue; Fever; Hypogammaglobulinemia; Lymphadenopathy; Lymphocytosis; Night Sweats; Paraproteinemia; Small Lymphocytic Lymphoma; Thrombocytopenia	Drug: Lenalidomide; Biological: Ofatumumab	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To evaluate efficacy and tolerability of the combination of ofatumumab and lenalidomide in patients with recurrent chronic lymphocytic leukemia (CLL).

OUTLINE:

Participants receive ofatumumab intravenously (IV) over 4 hours on days 1, 8, 15, and 22 of course 1, day 1 of courses 2-6, and day 1 of every even course beginning course 8. Beginning day 9 of course 1, participants also receive lenalidomide orally (PO) daily. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up at 6 months, then every 3 months thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Combination of Lenalidomide and Ofatumumab in Patients With Previously Treated Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (CLL/SLL)
• Actual Study Start Date: Jan 19, 2010
• Actual Primary Completion Date: Jan 31, 2018
• Actual Study Completion Date: Jan 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (lenalidomide, ofatumumab) Participants receive ofatumumab IV over 4 hours on days 1, 8, 15, and 22 of course 1, day 1 of courses 2-6, and day 1 of every even course beginning course 8. Beginning day 9 of course 1, participants also receive lenalidomide PO daily. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.	Drug: Lenalidomide; Given PO; Other Names: CC-5013 CC5013 CDC 501 Revlimid ; Biological: Ofatumumab; Given IV; Other Names: Arzerra GSK1841157 HuMax-CD20 HuMax-CD20, 2F2

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate [Up to 8 years]

   A Simon's two-stage minmax design will be used. Includes complete remission (CR) and partial remission (PR). Complete Response Requires the absence of disease signs and symptoms, and normalization of Peripheral blood and bone marrow. Partial Response it at lease a 50% reduction in disease signs and symptoms and normalization of peripheral blood.

Secondary Outcome Measures

1. Number of Participants With Tolerance of the Medication Combination [Up to 8 years]

   Incidence of grade 3 and 4 non-hematological toxicity in more than 50 percent of the participants. Will be monitored based on the Bayesian model (beta-binomial).

2. Progression Free Survival [Up to 8 years]

   The time from the start of therapy to death, disease progression, or the initiation of the next therapy. Disease progression is the loss of response or transformation to a more aggressive histology.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Understand and voluntarily sign an informed consent

• Patients with CLL or small lymphocytic lymphoma (SLL) with active disease: B-CLL Rai III-IV or earlier stage disease with evidence of "active disease" as defined by the National Cancer Institute (NCI)-sponsored working group 1) weight loss of > 10% in prior 6 months, 2) extreme fatigue, 3) fever or night sweats without evidence of infection, 4) worsening anemia or thrombocytopenia, 5) progressive lymphocytosis with a rapid lymphocyte doubling time, 6) marked hypogammaglobulinemia or paraproteinemia,

1. lymphadenopathy > 5 cm in diameter

• Prior treatment with purine analog based chemotherapy or chemoimmunotherapy

• Platelet count > or = to 30,000 mm^3

• Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) performance status of 0-2

• Creatinine clearance > 30 ml/min (calculated by 24 hours urine collection) or a glomerular filtration rate (GFR) > 30 ml/min estimated using the Cockcroft-Gault equation

• Total bilirubin less or equal to 2 mg/dl

• Alanine aminotransferase (ALT) less or equal to two times the upper limit of normal

• Disease free of prior malignancies for 3 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast. Patients with malignancies with indolent behavior such as prostate cancer treated with radiation or surgery can be enrolled in the study as long as they have a reasonable expectation to have been cured with the treatment modality received

• 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 starting lenalidomide and again within 24 hours prior to prescribing lenalidomide (prescriptions must be filled within 7 days) and prior to first ofatumumab administration 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 and continue it for 6 months after therapy has been completed. 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. All study participants must be registered into the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist

Exclusion Criteria:

• Known sensitivity to lenalidomide, other thalidomide derivatives or ofatumumab

• Documented prolymphocytic leukemia (prolymphocytes more than 55% in the blood)

• Known positivity for human immunodeficiency virus (HIV) or active hepatitis B or C. Positive serology for hepatitis B (HB) defined as a positive test for hepatitis B surface antigen (HBsAg). In addition, if negative for HBsAg positive but HBcAb positive regardless of HBsAg status, a HB deoxyribonucleic acid (DNA) test will be performed and if positive the subject will be excluded

• Pregnant or breast feeding females. Women of childbearing potential must have a negative pregnancy test at screening. Male subjects unable or unwilling to use adequate contraception methods from study start to one year after the last dose of protocol therapy

• Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis and tuberculosis. History of tuberculosis treated within the last five years or recent exposure to tuberculosis

• Any serious medical condition, laboratory abnormality, or psychiatric illness that places the subject at unacceptable risk if he/she were to participate in the study

• Patients with a recent history of deep vein thrombosis (DVT) or pulmonary embolus (PE), in the six months prior to enrollment are not eligible for this study

• Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to enrollment, whichever is longer, or currently participating in any other interventional clinical study

• Prior treatment with other monoclonal antibodies within 4 weeks prior to enrollment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	M D Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Alessandra Ferrajoli, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 17, 2010

More Information

Additional Information:

• MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT01002755
• Other Study ID Numbers: 2009-0283; NCI-2018-01829; 2009-0283; P30CA016672
• First Posted: Oct 27, 2009
• Last Update Posted: May 7, 2019
• Last Verified: Apr 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Thrombocytopenia; Lymphadenopathy; Agammaglobulinemia; Lymphocytosis; Paraproteinemias; Lenalidomide; Ofatumumab; Antibodies, Monoclonal

Study Results

Participant Flow

Arm/Group Title	Treatment (Lenalidomide, Ofatumumab)
Arm/Group Description	Participants receive ofatumumab IV over 4 hours on days 1, 8, 15, and 22 of course 1, day 1 of courses 2-6, and day 1 of every even course beginning course 8. Beginning day 9 of course 1, participants also receive lenalidomide PO daily. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Lenalidomide: Given PO Ofatumumab: Given IV
Period Title: Overall Study
STARTED	36
COMPLETED	36
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Lenalidomide, Ofatumumab)
Arm/Group Description	Participants receive ofatumumab IV over 4 hours on days 1, 8, 15, and 22 of course 1, day 1 of courses 2-6, and day 1 of every even course beginning course 8. Beginning day 9 of course 1, participants also receive lenalidomide PO daily. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Lenalidomide: Given PO Ofatumumab: Given IV
Overall Participants	36
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	64
Sex: Female, Male (Count of Participants)
Female	9 25%
Male	27 75%
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	3 8.3%
White	32 88.9%
More than one race	0 0%
Unknown or Not Reported	1 2.8%
Region of Enrollment (participants) [Number]
United States	36 100%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate
Description	A Simon's two-stage minmax design will be used. Includes complete remission (CR) and partial remission (PR). Complete Response Requires the absence of disease signs and symptoms, and normalization of Peripheral blood and bone marrow. Partial Response it at lease a 50% reduction in disease signs and symptoms and normalization of peripheral blood.
Time Frame	Up to 8 years

Outcome Measure Data

Analysis Population Description

Two participants were not evaluable for response.

Arm/Group Title	Treatment (Lenalidomide, Ofatumumab)
Arm/Group Description	Participants receive ofatumumab IV over 4 hours on days 1, 8, 15, and 22 of course 1, day 1 of courses 2-6, and day 1 of every even course beginning course 8. Beginning day 9 of course 1, participants also receive lenalidomide PO daily. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Lenalidomide: Given PO Ofatumumab: Given IV
Measure Participants	34
Count of Participants [Participants]	24 66.7%

2. Secondary Outcome

Title	Number of Participants With Tolerance of the Medication Combination
Description	Incidence of grade 3 and 4 non-hematological toxicity in more than 50 percent of the participants. Will be monitored based on the Bayesian model (beta-binomial).
Time Frame	Up to 8 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Lenalidomide, Ofatumumab)
Arm/Group Description	Participants receive ofatumumab IV over 4 hours on days 1, 8, 15, and 22 of course 1, day 1 of courses 2-6, and day 1 of every even course beginning course 8. Beginning day 9 of course 1, participants also receive lenalidomide PO daily. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Lenalidomide: Given PO Ofatumumab: Given IV
Measure Participants	36
Number [participants]	0 0%

3. Secondary Outcome

Title	Progression Free Survival
Description	The time from the start of therapy to death, disease progression, or the initiation of the next therapy. Disease progression is the loss of response or transformation to a more aggressive histology.
Time Frame	Up to 8 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Lenalidomide, Ofatumumab)
Arm/Group Description	Participants receive ofatumumab IV over 4 hours on days 1, 8, 15, and 22 of course 1, day 1 of courses 2-6, and day 1 of every even course beginning course 8. Beginning day 9 of course 1, participants also receive lenalidomide PO daily. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Lenalidomide: Given PO Ofatumumab: Given IV
Measure Participants	34
Median (95% Confidence Interval) [months]	16

Adverse Events

Time Frame	1 year
Arm/Group Title	Treatment (Lenalidomide, Ofatumumab)
Arm/Group Description	Participants receive ofatumumab IV over 4 hours on days 1, 8, 15, and 22 of course 1, day 1 of courses 2-6, and day 1 of every even course beginning course 8. Beginning day 9 of course 1, participants also receive lenalidomide PO daily. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Lenalidomide: Given PO Ofatumumab: Given IV
All Cause Mortality
	Treatment (Lenalidomide, Ofatumumab)
	Affected / at Risk (%)	# Events
Total	0/36 (0%)
Serious Adverse Events
	Treatment (Lenalidomide, Ofatumumab)
	Affected / at Risk (%)	# Events
Total	13/36 (36.1%)
Blood and lymphatic system disorders
Thrombosis	2/36 (5.6%)	2
Cardiac disorders
Atrial Fibrillation	1/36 (2.8%)	2
General disorders
Fatigue	1/36 (2.8%)	1
Fever	3/36 (8.3%)	4
Weakness	1/36 (2.8%)	1
Infections and infestations
Infection	3/36 (8.3%)	3
Meninogencephalitis	1/36 (2.8%)	1
Neutropenic Fever	1/36 (2.8%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma	1/36 (2.8%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/36 (5.6%)	4
Pulmonary Embolism	1/36 (2.8%)	1
Surgical and medical procedures
Appendectomy	1/36 (2.8%)	1
Hernia repair	1/36 (2.8%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Lenalidomide, Ofatumumab)
	Affected / at Risk (%)	# Events
Total	33/36 (91.7%)
Blood and lymphatic system disorders
Anemia	10/36 (27.8%)	10
Edema Limb	2/36 (5.6%)	2
Neutropenia	23/36 (63.9%)	23
Thrombocytopenia	12/36 (33.3%)	12
Eye disorders
Dry eye	2/36 (5.6%)	2
Gastrointestinal disorders
Constipation	12/36 (33.3%)	12
Diarrhea	15/36 (41.7%)	15
Distention/Bloating	2/36 (5.6%)	2
Nausea	9/36 (25%)	9
Vomiting	3/36 (8.3%)	3
General disorders
Cough	8/36 (22.2%)	8
Fatigue	16/36 (44.4%)	16
Fever	14/36 (38.9%)	14
Pain	16/36 (44.4%)	16
Sweating	2/36 (5.6%)	2
Immune system disorders
Tumor Flare	7/36 (19.4%)	7
Infections and infestations
Infection	20/36 (55.6%)	20
Investigations
Allergic Drug Reaction	8/36 (22.2%)	11
Metabolism and nutrition disorders
Hyperglycemia	2/36 (5.6%)	2
Hypomagnesemia	2/36 (5.6%)	2
Musculoskeletal and connective tissue disorders
Muscle Weakness	2/36 (5.6%)	2
Nervous system disorders
Insomnia	2/36 (5.6%)	2
Neurology other	5/36 (13.9%)	5
Respiratory, thoracic and mediastinal disorders
Dyspnea	5/36 (13.9%)	5
Pleural Effusion	2/36 (5.6%)	2
Pulmonary Other	3/36 (8.3%)	3
Skin and subcutaneous tissue disorders
Acne	3/36 (8.3%)	3
Dermatology/Skin	2/36 (5.6%)	2
Dry Skin	2/36 (5.6%)	2
Pruritis	6/36 (16.7%)	6
Rash/desquamation	2/36 (5.6%)	2

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.