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Trial record 1 of 38 for:    CLL idelalisib
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A Study of Idelalisib (GS1101, CAL101) + Ofatumumab in Previously Untreated CLL/SLL

This study has suspended participant recruitment.
(Due to safety of idelalisib in previously untreated CLL/SLL)
Sponsor:
Collaborators:
Gilead Sciences
GlaxoSmithKline
Information provided by (Responsible Party):
Jennifer R. Brown, MD, PhD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT02135133
First received: April 24, 2014
Last updated: May 25, 2017
Last verified: May 2017
  Purpose

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.


Condition Intervention Phase
Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Drug: Idelalisib Drug: Ofatumumab Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase II Study of Idelalisib (GS1101, CAL101) + Ofatumumab in Previously Untreated Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Leukemia (SLL)

Resource links provided by NLM:


Further study details as provided by Jennifer R. Brown, MD, PhD, Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Overall Response Rate of ofatumumab and idelalisib in previously untreated CLL/SLL participants in need of therapy [ Time Frame: 3 Years ]
    ORR of ofatumumab and idelalisib in previously untreated CLL/SLL participants in need of therapy


Secondary Outcome Measures:
  • CR rate and PFS of ofatumumab and idelalisib. [ Time Frame: 3 Years ]
    CR rate and PFS of ofatumumab and idelalisib.

  • ORR, CR rate and rate of nodal PR with lymphocytosis for idelalisib given alone for two months of therapy to previously untreated participants [ Time Frame: 3 Years ]
    ORR, CR rate and rate of nodal PR with lymphocytosis for idelalisib given alone for two months of therapy to previously untreated participants

  • Frequency of lymphocytosis with single agent idelalisib in previously untreated participants [ Time Frame: 3 Years ]
    Frequency of lymphocytosis with idelalisib in previously untreated participants

  • Frequency of serious adverse events while on treatment with idelalisib and ofatumumab [ Time Frame: 3 Years ]
    Overall safety of idelalisib in untreated participants and in combination with ofatumumab, as measured by adverse events, and serious adverse events in particular

  • Correlation of clinical response with known CLL molecular prognostic factors including FISH, IGHV, ZAP-70. [ Time Frame: 3 Years ]
    Correlation of clinical response with known CLL molecular prognostic factors including FISH, IGHV, ZAP-70.

  • Contribution of CT scans to response assessment [ Time Frame: 3 Years ]
    The frequency with which the use of CT scans in response assessment improves the predictive power of ORR for progression-free survival or time to next treatment.

  • Correlation of serum ofatumumab and/or idelalisib levels in vivo with response. [ Time Frame: 3 Years ]
    Serum ofatumumab and/or idelalisib levels in vivo with response.

  • Cell surface marker phenotype of circulating CLL cells. [ Time Frame: 3 Years ]
    Frequency with which idelalisib alters the cell surface marker phenotype of circulating CLL cells.

  • Impact of in vivo treatment with idelalisib on CLL cell sensitivity to therapy with antibodies or other kinase inhibitors. [ Time Frame: 3 Years ]
    CLL cell sensitivity to therapy with antibodies or other kinase inhibitors will be determined in patient cells treated in vivo with idelalisib.

  • Pharmacodynamic markers of PI3 kinase inhibition including AKT phosphorylation, production of T cell chemokines and response to CXCR 4/5. [ Time Frame: 3 Years ]
    Pharmacodynamic markers of PI3 kinase inhibition including AKT phosphorylation, production of T cell chemokines and response to CXCR 4/5.

  • Correlation of genetic alterations in PIK3CA or PIK3CD or other genes with response or resistance ot idelalisib [ Time Frame: 3 Years ]
    Mechanisms of response or resistance, specifically correlation with genetic alterations in PIK3CA or PIK3CD or other genes.

  • Influence of idelalisib treatment on intrinsic innate immune suppression and on regulatory T cells. [ Time Frame: 3 Years ]
    Influence of idelalisib treatment on intrinsic innate immune suppression and on regulatory T cells.

  • Prediction of response and resistance to idelalisib through biochemical and genetic analysis of the PI3K pathway. [ Time Frame: 3 Years ]
    Predictors of response and resistance to idelalisib through biochemical and genetic analysis of the PI3K pathway.


Estimated Enrollment: 50
Study Start Date: June 2014
Estimated Study Completion Date: March 2021
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Idelalisib & Ofatumumab
Idelalisib will be given orally continuously at 150 mg BID. On day 57, ofatumumab will begin with the 300 mg dose, given after idelalisib is taken. Ofatumumab will then be administered at 1000 mg weekly to complete 8 weeks (days 64, 71, 78, 85, 92, 99, 106) throughout Cycles 3 and 4. This will be followed by monthly ofatumumab on weeks 20, 24, 28, 32 to complete 4 additional cycles (5-8). The overall induction treatment period will then be 8 months, comprised of two months of single agent idelalisib followed by 6 months of ofatumumab with idelalisib. After the completion of the induction treatment, idelalisib will continue indefinitely in arbitrarily defined 28 day cycles in all participants who have not had excessive toxicity and do not have progressive disease.
Drug: Idelalisib
150 mg BID Oral Daily
Other Name: GS1101
Drug: Ofatumumab
Ofatumumab will then be administered at 1000 mg weekly to complete 8 weeks (days 64, 71, 78, 85, 92, 99, 106) throughout Cycles 3 and 4. This will be followed by monthly ofatumumab on weeks 20, 24, 28, 32 to complete 4 additional cycles (5-8).
Other Name: Arzerra

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 immunophenotype.
  • 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 infection; OR
  • 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 Gilbert's disease)
  • 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 document.

Exclusion Criteria:

  • 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 the participant.
  • 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 investigator.
  • 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 eligible.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02135133

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Isreal Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Dana-Farber Cancer Institute
Gilead Sciences
GlaxoSmithKline
Investigators
Principal Investigator: Jennifer Brown, MD, PhD Dana-Farber Cancer Institute
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Jennifer R. Brown, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT02135133     History of Changes
Other Study ID Numbers: 13-309
Study First Received: April 24, 2014
Last Updated: May 25, 2017

Keywords provided by Jennifer R. Brown, MD, PhD, Dana-Farber Cancer Institute:
Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma

Additional relevant MeSH terms:
Idelalisib
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 21, 2017