Chronic Lymphocytic Leukemia or Lymphocytic Small Cell Lymphoma without previous treatment MedDRA version: 20.0 Level: LLT Classification code 10051812 Term: Small cell lymphocytic lymphoma System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10008976 Term: Chronic lymphocytic leukemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Ofatumumab
Product Name: ARZERRA
Pharmaceutical Form: Solution for injection
INN or Proposed INN: OFATUMUMAB
CAS Number: 679818-59-8
Concentration unit: mg milligram(s)
Concentration type:
Sponsors
Fundación PETHEMA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Physically fit patients with treatment-naïve chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). 1. Adult patients with previously untreated CLL or SLL defined following IWCLL criteria (Hallek, 2008). 2. Must understand and voluntarily sign an informed consent form. 3. Age = 18 years at the time of signing the informed consent form and must be able to adhere to the study visit schedule and other protocol requirements. 4. Must have a documented diagnosis of CLL or SLL [IWCLL guidelines for diagnosis and treatment of CLL (Hallek, 2008)] meeting at least one of the following criteria: • Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia. • Massive (i.e. > 6 cm below the left costal margin) or progressive or symptomatic splenomegaly. • Massive nodes (i.e. > 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy. • Progressive lymphocytosis with an increase of > 50% over a 2 month period, or lymphocyte doubling time (LDT) of less than 6 months. • A minimum of any one of the following disease-related symptoms: unintentional weight loss = 10% within the previous 6 months, significant fatigue (i.e., ECOG PS 2; cannot work or unable to perform usual activities), fevers of greater than 38.0° C or 100.5F for 2 or more weeks without other evidence of infection, or night sweats for more than 1 month without evidence of infection. 5. Physically fit patients defined as CIRS =65 years) yes F.1.3.1 Number of subjects for this age range 42
Exclusion criteria
Exclusion criteria: 1. Prior treatment for CLL or SLL. 2. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent form. 3. Systemic infection that has not resolved prior to initiating study treatment in spite of adequate anti-infective therapy. 4. Pregnant or lactating females. 5. Participation in any clinical study or having taken any investigational therapy within 28 days prior to initiating study therapy. 6. Central nervous system (CNS) involvement as documented by spinal fluid cytology or imaging. 7. Prior history of malignancies, other than CLL, unless the patient has been free of the disease for = 3 years. Exceptions include the following: • Basal cell carcinoma of the skin • Squamous cell carcinoma of the skin • Carcinoma in situ of the cervix • Carcinoma in situ of the breast • Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b) 8. Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and/or Hepatitis C Virus (HCV) infection. 9. Any of the following laboratory abnormalities: • Serum creatinine = 2 x ULN or estimated Glomerular Filtration Rate (Cockroft GaultAppendix C) = 40 mL/min/1.73m2 • Absolute neutrophil count (ANC) 3 x upper limit of normal (ULN). • Serum total bilirubin > 1.5 x ULN, except in cases of Gilbert’s syndrome. 10. Presence of autoimmune haemolytic anemia or thrombocytopenia. 11. Disease transformation [i.e. Richter’s Syndrome (lymphomas) or prolymphocytic leukemia. 12. Major surgery within the last 28 days prior to registration. 13. History of stroke or intracranial haemorrhage within 6 months prior to enrolment. 14. Currently active, clinically significant cardiovascular disease or a history of myocardial infarction within 3 months prior to enrolment. 15. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists within 28 days of first dose of study drug. 16. Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator’s opinion, could compromise the subject’s safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the complete response rate obtained with the sequential combination of Ibrutinib and ofatumumab. Patients will receive 12 cycles of ibrutinib. Those obtaining a CR will continue with Ibrutinib alone, whereas patients not obtaining a CR will be treated with Ibrutinib and 6 cycles of ofatumumab. For the primary endpoint of the study, response will be evaluated after two months of completing ofatumumab.;Secondary Objective: • Overall response rate, including partial response with lymphocytosis • Evaluation of minimal residual disease (MRD) • Duration of response and progression-free survival • Safety: type, frequency, and severity of adverse events (AEs) and relationship of AEs to ibrutinib or the combination of ibrutinib and ofatumumab • Response rate in relationship to molecular and genetic prognostic factors • Evaluate biomarkers related to BCR and compensatory signaling pathways and their association with resistance to ibrutinib treatment • Immunological recovery • Overall survival;Primary end point(s): The primary end point is the complete response rate determined according to The IWCLL guidelines (Hallek, 2008);Timepoint(s) of evaluation of this end point: For the primary endpoint of the study, response will be evaluated after two months of completing ofatumumab. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Overall response rate, including partial response with lymphocytosis • Evaluation of minimal residual disease (MRD) • Duration of response and progression-free survival • Safety: type, frequency, and severity of adverse events (AEs) and relationship of AEs to ibrutinib or the combination of ibrutinib and ofatumumab • Response rate in relationship to molecular and genetic prognostic factors • Evaluate biomarkers related to BCR and compensatory signaling pathways and their association with resistance to ibrutinib treatment • Immunological recovery • Overall survival;Timepoint(s) of evaluation of this end point: Response will be assessed after 12 cycles of ibrutinib to determine to continue with ibrutinib alone (patients in CR) or to consolidate the response with ofatumumab (patients not in CR). The response to therapy will be assessed after 20 cycles of treatment (2 months after completing ofatumumab) for the primary objective of the study. In addition, the best overall response will be also determined. The best overall response is defined as the best response recorded from the start of treatment until progressive disease/recurrence. | — |
Countries
Spain
Contacts
Public ContactDr. Juan José Lahuerta Palacios
Fundación Pethema
Outcome results
None listed