Estudio de fase III, aleatorizado, multicéntrico y abierto, del inhibidor de la tirosina-cinasa de Bruton (BTK) ibrutinib frente a ofatumumab en pacientes con leucemia linfocítica crónica/linfoma linfocítico pequeño recidivante o resistente a tratamiento.A Randomized, Multicenter, Open-label, Phase 3 Study of the Bruton?s Tyrosine Kinase (BTK) Inhibitor Ibrutinib versus Ofatumumab in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
- Conditions
- leucemia linfocítica crónica/linfoma linfocítico pequeño recidivante o resistente a tratamiento.relapsed or refractory CLL/SLL.MedDRA version: 14.1Level: LLTClassification code 10060671Term: B-cell chronic lymphocytic leukemia/prolymphocytic leukemia/small lymphocytic lymphoma refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-000694-23-ES
- Lead Sponsor
- Pharmacyclics, Incorporated
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 350
1. Men and women ? 18 years of age
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
3. Life expectancy of > 4 months from the 1st dose of study medication
4. Diagnosis of CLL/SLL that meets published diagnostic criteria (Hallek 2008): a) Monoclonal B-cells (either kappa or lambda light chain restricted) that are clonally co expressing at least one B-cell marker (CD19, CD20, or CD23) and CD5, b) The diagnosis of CLL requires a history of lymphocytosis with a B-lymphocyte count ?5,000/µl while SLL patients are characterized by the same criteria with a circulating B lymphocyte count <5,000/µl. Prolymphocytes may comprise no more than 55% of blood lymphocytes
5. Active disease meeting at least 1 of the following IWCLL 2008 criteria for requiring treatment: a) Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (Hgb < 11 g/dL) and/or thrombocytopenia (platelets < 100,000/L), b) Massive, progressive, or symptomatic splenomegaly, c) Massive nodes, progressive, or symptomatic lymphadenopathy, d) Progressive lymphocytosis with an increase of > 50% over a 2-month period or a lymphocyte doubling time (LDT) of < 6 months. LDT may be obtained by linear regression extrapolation of absolute lymphocyte counts (ALC) obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In patients with initial blood lymphocyte counts of < 30 X 109/L (30,000/?L), 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 should be excluded, e) Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy, f) Constitutional symptoms, defined as one or more of the following disease-related symptoms or signs, i) Unintentional weight loss > 10% within the previous 6 months prior to Screening
ii) Significant fatigue; iii) Fevers higher than 100.5° F or 38 .0° C for 2 or more weeks prior to Screening without evidence of infection or iv) Night sweats for more than 1 month prior to Screening without evidence of infection
6. Must have received at least one prior therapy for CLL/SLL and not be appropriate for treatment or retreatment with purine analog based therapy, defined by at least one of the following criteria: a) Failure to respond (stable disease [SD] or disease progression on treatment), or a progression-free interval of less than 3 years from treatment with a purine analog based therapy and anti-CD20 containing chemoimmunotherapy regimen after at least two cycles, b) Age ? 70 years, or age ? 65 and the presence of co-morbidities (Cumulative Illness Rating Scale [CIRS] ? 6 or CrCl < 70 mL/min) that might place the patient at an unacceptable risk for treatment-related toxicity with purine analog based therapy, provided they have received >1 prior treatment including at least two cycles of an alkylating-agent based (or purine analog based) anti-CD20 antibody containing chemoimmunotherapy regimen. CIRS score can be determined utilizing a web-based tool.
c) History of purine analog-associated autoimmune anemia or autoimmune thrombocytopenia, d) FISH showing 17p del in ? 20% of cells (either at diagnosis or any time before study entry) either alone or in combination with other cytogenetic abnormalities, provided they have received at least one prior therapy
7. Measurable nodal disease by CT.
8. Meet the following labor
Patients will be ineligible for this study if they meet any of the following criteria:
1. Known central nervous system (CNS) lymphoma or leukemia
2. Any history of Richter?s transformation or prolymphocytic leukemia
3. No documentation of cytogenetic and/or FISH results reflecting 17p del status in records prior to first dose of study drug
4. Uncontrolled Autoimmune Hemolytic Anemia (AIHA) or ideopathic thrombocytopenia purpura (ITP), such as those patients with a declining hemoglobin (Hgb) level or platelet count secondary to autoimmune destruction within the 4 weeks prior to first dose of study drug or the need for daily corticosteroids >20 mg daily
5. Prior exposure to ofatumumab or to ibrutinib
6. Previous randomization in a PCI-32765/ibrutinib study
7. Received any chemotherapy, external beam radiation therapy, anticancer antibodies, or investigational drug within 30 days prior to first dose of study drug
8. Corticosteroid use within 1 week prior to 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. Patients requiring steroids at daily doses > 20 mg prednisone equivalent systemic exposure daily, or those who are administered steroids for leukemia control or white blood cell count lowering are excluded
9. Radio- or toxin-conjugated antibody therapy within 10 weeks prior to first dose of study drug
10. Prior autologous transplant within 6 months prior to first dose of study drug
11. Prior allogeneic stem cell transplant within 6 months prior to first dose of study drug
12. Major surgery within 4 weeks prior to first dose of study drug
13. History of prior malignancy, with the exception of the following:
a) Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to Screening and felt to be at low risk for recurrence by treating physician
b) Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease
c) Adequately treated cervical carcinoma in situ without current evidence of disease
14. Currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or history of myocardial infarction within 6 months prior to first dose with study drug
15. Unable to swallow capsules or disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption such as; malabsorption syndrome, resection of the small bowel, or poorly controlled inflammatory bowel disease affecting the small intestine
16. 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)
17. Known history of infection with human immunodeficiency virus (HIV)
18. Serologic status reflecting active hepatitis B or C infection. Patients with hepatitis B core antibody positive who are antigen negative will need to have a negative polymerase chain reaction (PCR) result prior to enrollment. Those who are hepatitis B antigen positive or PCR positive will be excluded
19. History of stroke or intracranial hemorrhage within 6 months prior to enrollment
20. Pregnant or lactating women
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method