A Study of Idelalisib (GS1101, CAL101) + Ofatumumab in Previously Untreated CLL/SLL
Phase: Phase 2
NCT ID: NCT02135133
(View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 13-309
This research study is evaluating a combination of drugs called Ofatumumab and Idelalisib as a possible treatment for Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Leukemia (SLL). The main purpose of this study is to examine the combination of the two drugs, Ofatumumab and Idelalisib, in participants who have been diagnosed with CLL/SLL and have not previously received treatment but do require treatment. The investigators hope to observe how participants' disease will be impacted by this treatment and whether they will benefit more from combining these drugs together rather than taking them separately. Both of these drugs have been used in treatment for CLL / SLL and information from those research studies suggests that these drugs may help patients with CLL/SLL. Ofatumumab is an antibody engineered in the lab against CD20, a protein on the surface of CLL cells, which is expressed in CLL. An antibody is a molecule your body creates to identify foreign substances so that it can destroy them. Ofatumumab has been FDA approved for treatment of CLL/SLL that has relapsed or progressed on other therapies. Idelalisib is a drug that blocks one of the signals inside the cells that cause this type of cancer to grow and survive. The investigators hope that combining Ofatumumab with Idelalisib will stop the growth of disease. In this research study, the investigators are evaluating the side effects of combining these two drugs, gathering information on the CLL/SLL disease process and how the study affects the patient's cells, as well as assessing the outcome of the disease. This combination of drugs has been previously tested, and appeared to be well tolerated.
Brigham and Women's Hospital, Massachusetts General Hospital, Dana-Farber Cancer Institute, Beth-Israel Deaconess Medical Center
Jennifer Brown, MD, PhD,
Dana-Farber Cancer Institute
Jeffery Barnes, MD,
Dana Farber Cancer Institute
Jon Arnason, MD,
Beth Israel Deaconess Medical Center
Dana-Farber Cancer Institute:
Beth-Israel Deaconess Medical Center:
Cancer Trials Call Center, 617-667-3060
Massachusetts General Hospital:
Cancer Trials Call Center, 877-789-6100
- Participants must meet the following criteria on screening examination to be eligible
to participate in the study:
- Subjects must have CLL / SLL, as documented by a history at some point of an absolute
peripheral blood B cell count > 5000, with a monoclonal B cell population
co-expressing CD19, CD5, and CD23, or if CD23 negative, then documentation of the
absence of t(11;14) or cyclin D1 overexpression. Alternatively patients with
lymphadenopathy in the absence of circulating disease will also be eligible for this
study if lymph node biopsy establishes the diagnosis of CLL with the above
- Participants must have measurable disease (lymphocytosis > 5,000, or palpable or CT
measurable lymphadenopathy > 1.5 cm, or bone marrow involvement >30%).
- Subjects must not have received any prior systemic therapy for CLL and currently have
an indication for treatment as defined by the IWCLL 2008 Guidelines:
- Massive or progressive splenomegaly; OR
- Massive lymph nodes, nodal clusters, or progressive lymphadenopathy; OR
- Grade 2 or 3 fatigue; OR
- Fever ≥ 100.5°F or night sweats for greater than 2 weeks without documented
- Presence of weight loss ≥ 10% over the preceding 6 months; OR
- Progressive lymphocytosis with an increase of ≥ 50% over a 2-month period or an
anticipated doubling time of less than 6 months; OR
- Evidence of progressive marrow failure as manifested by the development of or
worsening of anemia and or thrombocytopenia.
- ECOG performance status <2 (see Appendix A).
- Age ≥ 18 years. Because no dosing or adverse event data are currently available on
the use of idelalisib or ofatumumab in participants <18 years of age, children are
excluded from this study.
- Participants must have normal organ and marrow function as defined below:
- creatinine <2.0 times upper normal limit, total bilirubin <1.5 times upper normal
limit (unless due to disease involvement of liver, hemolysis or a known history of
- ALT <2.5 times upper normal limit (unless due to disease involvement of liver)
alkaline phosphatase <2.5 times upper normal limit (unless due to disease involvement
of the liver or bone marrow)
- Ability to understand and the willingness to sign a written informed consent
- Participants who exhibit any of the following conditions at screening will not be
eligible for admission into the study.
- Participants who have had any prior systemic therapy for CLL, or chemotherapy or
radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) for some other
indication prior to entering the study or those who have not recovered from adverse
events due to agents administered more than 4 weeks earlier.
- History of severe allergic reactions attributed to compounds of similar chemical or
biologic composition to ofatumumab or idelalisib.
- Subjects who have current active hepatic or biliary disease (with exception of
participants with Gilbert's syndrome, asymptomatic gallstones, liver metastases or
stable chronic liver disease per investigator assessment)
- 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
- Other past or current malignancy that could interfere with the interpretation of
outcome. Subjects who have been free of active malignancy for at least 2 years, or
have a history of completely resected non-melanoma skin cancer or successfully
treated in situ carcinoma, or whose malignancy will not interfere with the
interpretation of study results, are eligible.
- 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, tuberculosis and active Hepatitis C.
- History of significant cerebrovascular disease in the past 6 months or ongoing event
with active symptoms or sequelae
- Known HIV positive. HIV-positive individuals on combination antiretroviral therapy
are ineligible because of the potential for pharmacokinetic interactions with
idelalisib. In addition, these individuals are at increased risk of lethal infections
when treated with marrow-suppressive therapy. Appropriate studies will be undertaken
in participants receiving combination antiretroviral therapy when indicated.
- Clinically significant cardiac disease including unstable angina, acute myocardial
infarction within six months prior to randomization, congestive heart failure (NYHA
III-IV), and arrhythmia unless controlled by therapy, with the exception of extra
systoles or minor conduction abnormalities.
- Significant concurrent, uncontrolled medical condition including, but not limited to,
renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or
psychiatric disease which in the opinion of the investigator may represent a risk for
- Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In
addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB
DNA test will be performed and if positive the subject will be excluded.
- If HBV DNA is negative, subject may be included but must undergo HBV DNA PCR testing
at least every 2 months from the start of treatment until 12 months post treatment.
Prophylactic antiviral therapy may be initiated at the discretion of the
- Positive serology for hepatitis C (HC) defined as a positive test for HepC Ab, in
which case reflexively perform an HC RIBA immunoblot assay or hepatitis C viral load
to confirm the result. If the confirmatory test is negative the subject will be
- Pregnant or lactating women.
- Women of childbearing potential, including women whose last menstrual period was less
than one year prior to screening, unable or unwilling to use adequate contraception
from study start to 30 days after the last dose of protocol therapy. Adequate
contraception is defined as hormonal birth control, intrauterine device, double
barrier method or total abstinence.
- Male subjects unable or unwilling to use adequate contraception methods from study
start to 30 days after the last dose of protocol therapy.
- Participants using concomitant corticosteroids are allowed as long as the subject is
on the equivalent of 20mg/day or less of prednisone and has been on a stable dose for
at least two weeks prior to initiating therapy.