Combination of Lenalidomide and Ofatumumab in Patients With Previously Treated Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (CLL/SLL)
18 Years
N/A
Both
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Trial Information
Combination of Lenalidomide and Ofatumumab in Patients With Previously Treated Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (CLL/SLL)
The Study Drugs:
Lenalidomide is designed to change the body's immune system. It may also interfere with the
development of tiny blood vessels that help support tumor growth. Therefore, in theory, it
may decrease or prevent the growth of cancer cells.
Ofatumumab is designed to bind to the surface of a type of white blood cells called B-cells
and destroy them. The cancer cells in B-CLL/SLL are B-cells.
Study Drug Administration:
Each cycle is 28 days.
If you are found to be eligible to take part in this study, you will receive ofatumumab by
vein over 4 hours at the following times:
- On Days 1, 8, 15, and 22 of Cycle 1.
- On Day 1 of Cycles 2-6.
- On Day 1 of every even cycle beginning Cycle 8 (Cycles 8,10,12, and so on).
Beginning on Day 9 of Cycle 1, you will take lenalidomide by mouth every day.
Swallow lenalidomide capsules whole with a glass of water at the same time each day. Do not
break, chew, or open the capsules. If you miss a dose of lenalidomide, take it as soon as
you remember on the same day. If you miss taking your dose for the entire day, take your
regular dose the next scheduled day (do NOT take double your regular dose to make up for the
missed dose). If you take more than the prescribed dose of lenalidomide you should seek
emergency medical care if needed and contact study staff right away. Any unused lenalidomide
should be returned as instructed through the RevAssist® program.
On Days 1-14 of Cycle 1, you will take allopurinol to help prevent side effects. You will
take this by mouth with 1 glass of water 1 time a day. If the doctor thinks it is needed,
you will continue to take allopurinol.
If the doctor thinks it is needed, you may take aspirin or low molecular weight heparin to
help prevent blood clots.
If the doctor thinks it is needed, you may take medicine to help prevent return of hepatitis
B infection.
You should drink at least 8-10 cups of water each day for the first 14 days of Cycle 1 (
this includes the 1 with medications).
Study Visits:
One (1) time a week for the first 5 weeks, then 1 time every 2 weeks (if the dose of
lenalidomide has been changed), and then every 4 weeks, blood (about 2-3 teaspoons) will be
drawn for routine tests.
On Day 28 of Cycles 3, 7, 13, 19, and 23:
- You will have a physical exam, including measurement of your vital signs.
- Your performance status will be recorded
- Urine will be collected for routine tests.
- You will have a bone marrow aspiration and biopsy to check the status of the disease.
If you continue past 23 cycles, once every 6-12 cycles (+ 14 days):
- Blood (about 2-3 teaspoons) will be drawn for routine tests.
- If the doctor thinks it is needed, you will have a bone marrow biopsy and aspirate to
check the status of the disease .
If the doctor thinks it is needed, extra blood (about 2-3 teaspoons) will be drawn for
routine tests and at any time during the study.
If you have a type of hepatitis B called HBcAb, you are at risk of having hepatitis B
infection during treatment with ofatumumab. Every 2 months, blood (about 1/2 teaspoon each
time) will be drawn to check for hepatitis B infection.
Pregnancy Testing:
If you are a woman who is able to become pregnant, you will have blood (about 1 teaspoon) or
urine pregnancy tests 1 time a week for the first 28 days of the study, then every 28 days
while on study, when you stop the study, and at 28 days after off study.
If you are a woman who is able to become pregnant and your menstrual cycles are irregular,
you will have blood (about 1 teaspoon) or urine pregnancy tests 1 time a week for the first
28 days, then every 14 days while on study, when you stop the study, and at 14 and 28 days
after off study.
Length of Study:
You will be on study for about 2 years. You will be taken off study early if you have
intolerable side effects or the disease gets worse.
If the doctor thinks you are benefiting, you may be able to continue taking lenalidomide for
as long as you are benefitting. If you continue, you will follow the same schedule of dosing
and study visit schedule.
Follow-Up:
About 6 months after you go off study, blood (about 1 teaspoon) will be drawn for routine
tests. You will not need to come to M. D. Anderson for this blood draw, it can be performed
by your local doctor.
The study staff will call you every 3 months from then on unless you begin a new treatment
and ask you how you are doing. This phone call will take about 2-3 minutes.
After you are off study, if you have hepatitis B, blood (about 1/2 teaspoon each time) will
be drawn every 2-3 months up to 6 months after the last dose of ofatumumab.
This is an investigational study. Lenalidomide is FDA approved for the treatment of
multiple myeloma and some myelodysplastic syndromes. Ofatumumab is FDA approved and
commercially available for the treatment of CLL. The combination of lenalidomide and
ofatumumab to treat CLL or SLL is investigational.
Up to 36 patients will take part in this study. All will be enrolled at M. D. Anderson.
Inclusion Criteria:
1. Patients age > 18 years at the time of signing informed consent. Understand and
voluntarily sign an informed consent.
2. Patients with CLL or SLL with active disease: B-CLL Rai III-IV or earlier stage
disease with evidence of "active disease" as defined by the 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, 7) lymphadenopathy >5 cm in diameter.
3. Prior treatment with purine analog based chemotherapy or chemoimmunotherapy.
4. platelet count > or = to 30,000 mm3
5. ECOG/WHO performance status of 0-2
6. Adequate renal function indicated by creatinine clearance > 30ml/min (calculated by
24 hours urine collection) or a GFR > 30 ml/min estimated using the Cockcroft-Gault
equation . Adequate hepatic function indicated as total bilirubin less or equal to 2
mg/dl and ALT less or equal to two times the upper limit of normal.
7. 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.
8. 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
9. Cont. from #8 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:
1. Known sensitivity to lenalidomide, other thalidomide derivatives or ofatumumab.
2. Documented prolymphocytic leukemia (prolymphocytes more than 55% in the blood).
3. Known positivity for HIV or active hepatitis B or C. Positive serology for hepatitis
B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg
positive but HBcAb positive regardless of HBsAg status, a HB DNA test will be
performed and if positive the subject will be excluded.
4. 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
5. 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.
6. 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.
7. 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.
8. 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
9. Prior treatment with other monoclonal antibodies within 4 weeks prior to enrollment.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Overall Response
Outcome Time Frame:
Responses assessed after 3, 6, 12, 18 and 24 cycles (each cycle is 28 days) and every 6-12 months as clinically indicated.
Safety Issue:
No
Principal Investigator
Alessandra Ferrajoli, MD
Investigator Role:
Study Chair
Investigator Affiliation:
UT MD Anderson Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
2009-0283
NCT ID:
NCT01002755
Start Date:
January 2010
Completion Date:
Related Keywords:
- Chronic Lymphocytic Leukemia
- Small Lymphocytic Lymphoma
- Leukemia
- CLL
- SLL
- Lenalidomide
- Ofatumumab
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
- Lymphoma
Name | Location |
|---|---|
| UT MD Anderson Cancer Center | Houston, Texas 77030 |
