Chronic Lymphocytic Leukemia Clinical Trial
Acalabrutinib, Obinutuzumab and Chlorambucil in Treatment naïve CLL
This study is evaluating the efficacy of obinutuzumab in combination with chlorambucil (Arm A) compared with acalabrutinib in combination with obinutuzumab (Arm B) for the treatment of previously untreated leukemia-cll/" >chronic lymphocytic leukemia (CLL).
ELEVATE-TN is a global, phase 3, multicenter, open-label study in patients with treatment-naive chronic lymphocytic leukemia (CLL). Study enrollment is completed. The study randomized a total of 535 subjects in 142 study sites in 18 countries between 14 September 2015 through 08 February 2017. Patients were randomly assigned to receive Acalabrutinib and Obinutuzumab, Acalabrutinib monotherapy, or Obinutuzumab and oral Chlorambucil. The primary endpoint was progression-free survival between the two combination-therapy groups, defined as the time from randomization until disease progression by use of iwCLL 2008 criteria, or death, assessed by independent review committee (IRC). Crossover to Acalabrutinib was allowed in patients who progressed on Obinutuzumab-Chlorambucil.
The results of this study provide new evidence for therapy in patients with treatment-naive chronic lymphocytic leukemia by showing the efficacy of Acalabrutinib used with or without Obinutuzumab compared with chemoimmunotherapy.
Currently the study is in maintenance phase, with more than 430 subjects on study, to generate more evidence. We are not expecting any significant change in the near future.
Men and women:
a. ≥ 65 years of age OR b. > 18 and < 65 years of age, provided that they meet at least one of the following criteria: i. Creatinine clearance 30 to 69 mL/min using the Cockcroft-Gault equation ii. A score higher than 6 on the CIRS-G (Appendix L).
ECOG performance status of 0, 1, or 2.
Diagnosis of CD20+ CLL that meets published diagnostic criteria (Hallek 2008):
Monoclonal B cells (either kappa or lambda light chain restricted) that are clonally co-expressing ≥ 1 B-cell marker (CD19, CD20, or CD23) and CD5.
Prolymphocytes may comprise ≤ 55% of blood lymphocytes.
Presence of ≥ 5 x 109 B lymphocytes/L (5000 μL) in the peripheral blood (at any point since diagnosis)
Active disease meeting ≥ 1 of the following IWCLL 2008 criteria for requiring treatment:
Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin < 10 g/dL) and/or thrombocytopenia (platelets < 100,000/μL).
Massive (i.e., ≥ 6 cm below the left costal margin), progressive, or symptomatic splenomegaly.
Massive nodes (i.e., ≥ 10 cm in the longest diameter), progressive, or symptomatic lymphadenopathy.
Progressive lymphocytosis with an increase of > 50% over a 2-month period or a LDT of < 6 months. LDT may be obtained by linear regression extrapolation of ALC obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In subjects with initial blood lymphocyte counts of < 30 x 109/L (30,000/μL), LDT should not be used as a single parameter to define indication for treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (e.g., infections) should be excluded.
Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy.
Constitutional symptoms documented in the subject's chart with supportive objective measures, as appropriate, defined as ≥ 1 of the following disease-related symptoms or signs:
i. Unintentional weight loss ≥ 10% within the previous 6 months before Screening.
ii. Significant fatigue (i.e., ECOG performance status 2; inability to work or perform usual activities).
iii. Fevers higher than 100.5°F or 38.0°C for 2 or more weeks before Screening without evidence of infection.
iv. Night sweats for > 1 month before Screening without evidence of infection.
This criterion was deleted as of Protocol Amendment 3.
Meet the following laboratory parameters:
ANC ≥ 750 cells/μL (0.75 x 109/L), or ≥ 500 cells/μL (0.50 x 109/L) in subjects with documented bone marrow involvement, and independent of growth factor support 7 days before assessment.
Platelet count ≥ 50,000 cells/μL (50 x 109/L), or ≥ 30,000 cells/μL (30 x 109/L) in subjects with documented bone marrow involvement, and without transfusion support 7 days before assessment. Subjects with transfusion-dependent thrombocytopenia are excluded.
Serum AST and ALT/SGPT ≤ 3.0 x ULN.
Total bilirubin ≤ 1.5 x ULN.
Estimated creatinine clearance (i.e., eGFR using Cockcroft-Gault) ≥ 30 mL/min
Able to receive all outpatient treatment, all laboratory monitoring, and all radiologic evaluations.
Women who are sexually active and can bear children must agree to use highly effective forms of contraception while on the study and for 2 days after the last dose of acalabrutinib or 18 months after the last dose of obinutuzumab in combination with chlorambucil, whichever is longer. Highly effective forms of contraception are defined in Section 6.4.4.
Men who are sexually active and can beget children must agree to use highly effective forms of contraception during the study and for 90 days after the last dose of obinutuzumab or chlorambucil, whichever is later. Highly effective forms of contraception are defined in Section 6.4.4.
Men must agree to refrain from sperm donation during the study and for 90 days after the last dose of obinutuzumab or chlorambucil, whichever is later.
Must be willing and able to adhere to the study visit schedule, understand and comply with other protocol requirements, and provide written informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations). Note vulnerable subjects, as defined in International Conference on Harmonisation (ICH) GCP, are not allowed on this protocol (e.g., prisoners or institutionalized subjects).
Any prior systemic treatment for CLL (note: Prior localized radiotherapy is allowed).
Known CNS lymphoma or leukemia.
Known prolymphocytic leukemia or history of, or currently suspected, Richter's syndrome.
Missing or incomplete documentation of FISH results reflecting the presence or absence of 17p del and the percentage of cells with the deletion in subject records before randomization.
Uncontrolled AIHA or ITP defined as declining hemoglobin or platelet count secondary to autoimmune destruction within the screening period or requirement for high doses of steroids (> 20 mg daily of prednisone daily or equivalent).
Corticosteroid use > 20 mg within 1 week before first dose of study drug, except as indicated for other medical conditions such as inhaled steroid for asthma, topical steroid use, or as premedication for administration of study drug or contrast. For example, subjects requiring steroids at daily doses > 20 mg prednisone equivalent systemic exposure daily, or those who are administered steroids for leukemia control or WBC count lowering are excluded.
Major surgery within 4 weeks before first dose of study drug.
History of prior malignancy except for the following:
Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years before Screening and felt to be at low risk for recurrence by treating physician.
Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled non-melanomatous skin cancer.
Adequately treated cervical carcinoma in situ without current evidence of disease.
Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or QTc > 480 msec at screening.
Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or gastric bypass, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
Uncontrolled active systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment) or ongoing intravenous anti-infective treatment.
Known history of infection with HIV. 13. Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
14. Serologic status reflecting active hepatitis B or C infection. Subjects with hepatitis B core antibody positive who are surface antigen negative or who are hepatitis C antibody positive will need to have a negative PCR result before randomization. Those who are hepatitis B surface antigen positive or hepatitis B PCR positive and those who are hepatitis C PCR positive will be excluded.
15. History of stroke or intracranial hemorrhage within 6 months before randomization.
16. Known history of a bleeding diathesis (e.g., hemophilia, von Willebrand disease).
17. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon) within 7 days of first dose of study drug.
18. Requires treatment with proton-pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole).
19. Breast feeding or pregnant. 20. Current life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the subject's safety or put the study at risk.
21. Concurrent participation in another therapeutic clinical trial. 22. Requires treatment with a strong CYP3A inhibitor/inducer. 23. Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening.
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There are 151 Locations for this study
Phoenix Arizona, 85016, United States
Anaheim California, 92801, United States
Los Angeles California, 90017, United States
Los Angeles California, 90033, United States
Los Angeles California, 90095, United States
Oxnard California, 93030, United States
Palo Alto California, 94304, United States
Aurora Colorado, 80045, United States
Lone Tree Colorado, 80124, United States
Washington District of Columbia, 20007, United States
Fort Myers Florida, 33901, United States
Jacksonville Florida, 32224, United States
Tallahassee Florida, 32308, United States
Tallahassee Florida, 32308, United States
Tampa Florida, 33612, United States
Niles Illinois, 60714, United States
Lafayette Indiana, 47904, United States
Wichita Kansas, 67214, United States
Louisville Kentucky, 40207, United States
New Orleans Louisiana, 70112, United States
COL Maryland, 21044, United States
Rochester Minnesota, 55905, United States
Saint Cloud Minnesota, 56303, United States
Billings Montana, 59102, United States
Brick New Jersey, 08724, United States
Hackensack New Jersey, ?0760, United States
Lake Success New York, 11042, United States
New York New York, 10029, United States
Blue Ash Ohio, 45242, United States
Canton Ohio, 44719, United States
Columbus Ohio, 43210, United States
Nashville Tennessee, 37203, United States
Austin Texas, 78705, United States
Bedford Texas, 76022, United States
Dallas Texas, 75230, United States
Fort Sam Houston Texas, 78234, United States
Houston Texas, 77030, United States
New Braunfels Texas, 78130, United States
Round Rock Texas, 76508, United States
San Antonio Texas, 78258, United States
Texas City Texas, 77591, United States
Tyler Texas, 75702, United States
Salt Lake City Utah, 84112, United States
Roanoke Virginia, 24014, United States
Seattle Washington, 98109, United States
Seattle Washington, 98122, United States
Spokane Washington, 99208, United States
Tacoma Washington, 98405, United States
Yakima Washington, 98902, United States
Northwest WA Wisconsin, 20007, United States
Darlinghurst , 2010, Australia
Frankston , 3199, Australia
Geelong , 3220, Australia
South Brisbane , QLD 4, Australia
Waratah NSW , 2298, Australia
Wollongong , 2500, Australia
Woodville , 5011, Australia
Brugge , 8000, Belgium
Brussels , 1090, Belgium
Bruxelles , 1200, Belgium
Ghent , 9000, Belgium
Kortrijk , 8500, Belgium
Leuven , 3000, Belgium
Roeselare , 8900, Belgium
Wilrijk , 2610, Belgium
Yvoir , 5530, Belgium
Barretos , 14784, Brazil
Florianopolis , 88034, Brazil
Passo Fundo , 99010, Brazil
Porto Alegre , 90035, Brazil
Porto Alegre , 90470, Brazil
Sao Paulo , 155, Brazil
Vancouver British Columbia, V5Z 4, Canada
Halifax Nova Scotia, B3H2Y, Canada
Quebec City , G1J 1, Canada
Saint John , E2L 4, Canada
Winnipeg , R3E 0, Canada
Santiago , 83804, Chile
Temuco , 48104, Chile
Medellin , 05003, Colombia
Monteria , 11022, Colombia
Bobigny , 93000, France
Dijon , 21000, France
Pierre-Benite , 69310, France
Strasbourg Cedex , 67098, France
Villejuif , 94800, France
Aschaffenburg , 63739, Germany
Bielefeld , 33604, Germany
Erlangen , 91052, Germany
Heilbronn , 74078, Germany
Warzburg , 97080, Germany
Budapest , 1085, Hungary
Budapest , 1122, Hungary
Debrecen , 4032, Hungary
Kaposvár , 7400, Hungary
Szolnok , 5004, Hungary
Ashkelon , 78306, Israel
Beer Sheva , 84101, Israel
Haifa , 31000, Israel
Haifa , 31096, Israel
Haifa , 34362, Israel
Jerusalem , 91031, Israel
Nahariya , 22100, Israel
Petah Tikvah , 49100, Israel
Petah Tikvah , 49102, Israel
Rehovot , 76100, Israel
Tel Aviv , 64239, Israel
Tel Hashomer , 52621, Israel
Tiberias , 15208, Israel
Alessandria , 15100, Italy
Aviano , 33081, Italy
Brescia , 25123, Italy
Firenze , 50134, Italy
Meldola , 47014, Italy
Milano , 20132, Italy
Parma , , Italy
Ravenna , 48121, Italy
Rimini , 47900, Italy
Rome , 168, Italy
Rozzano , 20089, Italy
Kaunas , LT-50, Lithuania
Klaipeda , LT-92, Lithuania
Vilnius , LT-08, Lithuania
Auckland , ?0620, New Zealand
Otahuhu , 2025, New Zealand
Tauranga , 3112, New Zealand
Bydgoszcz , 85-16, Poland
Gdansk , 80-12, Poland
Gdynia , 81-51, Poland
Krakow , 30-51, Poland
Lodz , 93-51, Poland
Lublin , 20-08, Poland
Olsztyn , 10-22, Poland
Opole , 46-02, Poland
Slupsk , 76-20, Poland
Barcelona , ?0804, Spain
Madrid , 28006, Spain
Madrid , 28031, Spain
Madrid , 28041, Spain
Majadahonda , 28222, Spain
Santander , 39008, Spain
Gothenburg , 41345, Sweden
Linkoping , 58185, Sweden
Lund , SE-22, Sweden
Orebro , 701 8, Sweden
Bournemouth , BH7 7, United Kingdom
Cambridge , CB2 0, United Kingdom
Leeds , LS9 7, United Kingdom
Leicester , LE1 7, United Kingdom
London , SE5 9, United Kingdom
Plymouth , PL6 8, United Kingdom
Southampton , SO16 , United Kingdom
Truro , TR1 3, United Kingdom
Wolverhampton , WV10 , United Kingdom
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