Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma MedDRA version: 17.0 Level: LLT Classification code 10008976 Term: Chronic lymphocytic leukemia System Organ Class: 100000004864
Conditions
Sponsors
Infinity Pharmaceuticals, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. =18 years of age 2. Diagnosis of active CLL or SLL that meets at least one of the IWCLL 2008 criteria for requiring treatment (Binet Stage = B and/or Rai Stage = I) 3. Disease that has progressed during or relapsed after at least one previous CLL/SLL therapy 4. Not appropriate for treatment with a purine-based analogue regimen (per NCCN or ESMO guidelines), including relapse =36 months from a purine-based chemoimmunotherapy regimen or relapse =24 months from a purine-based monotherapy regimen 5. A cytogenetics or FISH analysis of the leukemic cells within 24 months of randomization is required to document the presence or absence of del(17p). Note: if a sample from within 24 months is not available, it should be collected as part of the screening laboratory evaluation 6. Measurable disease with a lymph node or tumor mass =1.5 cm in at least one dimension as assessed by computed tomography (CT) 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (corresponds to Karnofsky Performance Status [KPS] =60%) 8. Willingness by subject to be randomized to receive either ofatumumab or IPI-145 at the dose and schedule defined in the protocol 9. For women of childbearing potential (WCBP): negative serum ß-human chorionic gonadotropin (ßhCG) pregnancy test within 1 week before randomization (WCBP defined as a sexually mature woman who has not undergone surgical sterilization or who has not been naturally post-menopausal for at least 24 consecutive months [women =55 years] or 12 consecutive months [women >55 years]) 10. Willingness of male and female subjects who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control from the first dose of study drug to 30 days after the last dose of IPI-145 and for 12 months after last dose of ofatumumab. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception 11. Ability to voluntarily sign consent for and adhere to the entire study visit schedule and all protocol requirements 12. Signed and dated institutional review board (IRB)/independent ethics committee (IEC)-approved informed consent form (ICF) before any study specific screening procedures are performed Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 207 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: 1. History of Richter's transformation or prolymphocytic leukemia 2. Autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP) that is uncontrolled or requiring >20 mg QD of prednisone (or equivalent) to maintain hemoglobin >8.0 g/dL or platelets >10,000 µL without transfusion support 3. Prior allogeneic transplant (prior autologous stem cell transplant >6 months prior to study entry is permitted) 4. Known central nervous system (CNS) lymphoma or leukemia; subjects with symptoms of CNS disease must have a negative CT scan or negative diagnostic lumbar puncture prior to randomization 5. Prior exposure to a PI3K inhibitor (eg, GS-1101, IPI-145) or a BTK inhibitor 6. Use of any of the following medications or procedures within the specified timeframe: - Use of live or live attenuated vaccines within 30 days prior to randomization - Chemotherapy, radiation therapy, or ablative therapy within 3 weeks of randomization - Tyrosine kinase inhibitor within 7 days of randomization - Other investigational therapy (not included above) within 3 weeks of randomization 7. History of tuberculosis treatment within the preceding two years 8. Ongoing systemic bacterial, fungal, or viral infections at the time of initiation of study treatment (defined as requiring intravenous [IV] antimicrobial, antifungal or antiviral agents) - Subjects on antimicrobial, antifungal or antiviral prophylaxis are not specifically excluded if all other inclusion/exclusion criteria are met and there is no evidence of active infection at randomization 9. Human immunodeficiency virus (HIV) infection 10. Prior, current or chronic hepatitis B or hepatitis C infection 11. History of alcohol abuse or chronic liver disease (other than metastatic disease to the liver) 12. History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months 13. Prior surgery or gastrointestinal dysfunction that may affect drug absorption (eg, gastric bypass surgery, gastrectomy) 14. Major surgery or invasive intervention within 4 weeks prior to randomization 15. Pregnant or breastfeeding women
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To examine the efficacy of IPI-145 monotherapy versus ofatumumab monotherapy in subjects with relapsed or refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL);Secondary Objective: •To determine the safety of IPI-145 in subjects with CLL and SLL •To evaluate the pharmacokinetics (PK) of IPI-145 and, if applicable, its metabolite(s) ;Primary end point(s): Progression free survival (PFS), defined as time from randomization to the first documentation of progressive disease (PD) or death due to any cause;Timepoint(s) of evaluation of this end point: Screening, cycles 3, 5, 7, 11, 15 and 19, and early termination from study treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ORR, Lymph node response rate, Hematologic improvement;Timepoint(s) of evaluation of this end point: Screening, cycles 3, 5, 7, 11, 15 and 19, and early termination from study treatment | — |
Countries
Australia, Austria, Belgium, France, Germany, Greece, Hungary, Italy, Latvia, New Zealand, Spain, United Kingdom, United States
Contacts
Public ContactDarlene Noci
Infinity Pharmaceuticals, Inc
Outcome results
None listed