A Phase 3 Extension Study of Duvelisib and Ofatumumab in Patients With CLL/SLL Previously Enrolled in Study IPI-145-07
Last updated on April 2022Recruitment
- Recruitment Status
- Completed
- Estimated Enrollment
- 150
Inclusion Criteria
- Platelet count ≥10,000 μL with or without transfusion support
- Hemoglobin ≥8.0 g/dL with or without transfusion support
- Measurable disease with a lymph node or tumor mass >1.5 cm in at least one dimension as assessed by computed tomography (CT)
- ...
- Platelet count ≥10,000 μL with or without transfusion support
- Hemoglobin ≥8.0 g/dL with or without transfusion support
- Measurable disease with a lymph node or tumor mass >1.5 cm in at least one dimension as assessed by computed tomography (CT)
- Total bilirubin ≤1.5 x ULN
- Ability to voluntarily sign consent for and adhere to the entire study visit schedule and all protocol requirements
- Signed and dated institutional review board (IRB)/independent ethics committee (IEC)-approved informed consent form (ICF) before any study specific screening procedures are performed
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- For women of childbearing potential (WCBP): negative serum β-human chorionic gonadotropin (βhCG) pregnancy test within 1 week before first dose (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])
- Diagnosis of active CLL or SLL that meets at least 1 of the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria for requiring treatment
- Serum creatinine ≤2.0 x ULN
- Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≤3 x upper limit of normal (ULN)
- 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 duvelisib and for 12 months after last dose of ofatumumab. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception
- Received either IPI-145 or ofatumumab while participating in study IPI-145-07 and experienced radiologically-confirmed disease progression
Exclusion Criteria
- Pregnant or breastfeeding women
- Concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix, bladder, or prostate not requiring treatment. Subjects with previous malignancies are eligible provided that they have been disease-free for ≥2 years
- History of alcohol abuse or chronic liver disease (other than metastatic disease to the liver)
- ...
- Pregnant or breastfeeding women
- Concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix, bladder, or prostate not requiring treatment. Subjects with previous malignancies are eligible provided that they have been disease-free for ≥2 years
- History of alcohol abuse or chronic liver disease (other than metastatic disease to the liver)
- Use of any anticancer medication from documented PD on Study IPI-145-07 to enrollment (Note: corticosteroids to manage CLL/SLL-related symptoms are allowed)
- Prior, current, or chronic hepatitis B or hepatitis C infection
- History of Richter's transformation or prolymphocytic leukemia
- Known central nervous system (CNS) lymphoma or leukemia; subjects with symptoms of CNS disease must have a negative computed tomography (CT) scan or negative diagnostic lumbar puncture prior to first dose
- Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition), or any important medical illness or abnormal laboratory finding that would, in the Investigator's judgment, increase the subject's risk while participating in this study
- Baseline QT interval corrected with Fridericia's method (QTcF) >480 ms NOTE: this criterion does not apply to subjects with a right or left bundle branch block (BBB)
- Subjects to receive ofatumumab: hypersensitivity to ofatumumab or its excipients.
- Subjects to receive duvelisib: Administration of medications or foods that are strong inhibitors or inducers of cytochrome P450 (CYP) 3A within 2 weeks of starting duvelisib
- History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months
- Greater than 3 months from confirmed progressive disease on Study IPI-145-07
- Prior surgery or gastrointestinal dysfunction that may affect drug absorption (eg, gastric bypass surgery, gastrectomy)
- Autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenia purpura (ITP) that is uncontrolled or requires >20 mg daily (QD) of prednisone (or equivalent) to maintain hemoglobin >8.0 g/dL or platelets >10,000 μL without transfusion support
- Discontinued study participation in Verastem-sponsored IPI-145-07 study
- Unable to receive prophylactic treatment for pneumocystis and herpes simplex virus (HSV)
- Major surgery or invasive intervention within 4 weeks prior to first dose
- Human immunodeficiency virus (HIV) infection
- Ongoing systemic bacterial, fungal, or viral infections at the time of initiation of study treatment (defined as requiring 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 Screening and/or Cycle 1 Day 1 (predose))
Summary
- Conditions
- Chronic Lymphocytic Leukemia
- Small Lymphocytic Lymphoma
- Type
- Interventional
- Phase
- Phase 3
- Design
- Allocation: Non-Randomized
- Intervention Model: Parallel Assignment
- Masking: None (Open Label)
- Primary Purpose: Treatment
Participation Requirements
- Age
- Between 18 years and 125 years
- Gender
- Both males and females
Description
This is an open-label, two- arm, extension study designed to enable subjects who have experienced radiologically- confirmed disease progression in Study IPI-145-07 to receive the alternative treatment (either IPI-145 or ofatumumab) than what was received during study IPI-145-07. Subjects who have pr...
This is an open-label, two- arm, extension study designed to enable subjects who have experienced radiologically- confirmed disease progression in Study IPI-145-07 to receive the alternative treatment (either IPI-145 or ofatumumab) than what was received during study IPI-145-07. Subjects who have previously received ofatumumab in study IPI-145-07 will receive a starting dose of 25 mg IPI-145 BID continuously in a 21 day cycle for Cycle 1 followed by 28- day treatment cycles thereafter for up to 11 cycles or until disease progression, discontinuation from study participation, or start of subsequent therapy, whichever comes first. After completing approximately 11 cycles of treatment with duvelisib, subjects who, in the judgment of the Investigator, may derive benefit from continued treatment may continue to receive additional cycles of duvelisib until disease progression or unacceptable toxicity. However, to receive additional cycles of duvelisib beyond 11 cycles, subjects must have evidence of response and CLL/SLL requiring treatment according to the IWCLL/IWG by Cycle 12 Day 1. Subjects who have previously received IPI-145 in study IPI-145-07 will receive a starting dose of 300 mg ofatumumab on Day 1 followed by seven weekly doses of 2000 mg. Thereafter, subjects will receive 2000 mg ofatumumab once every month for four months unless disease progression or unacceptable toxicity occurs. Administration of ofatumumab will not exceed the 12 doses (within 7 cycles).
Inclusion Criteria
- Platelet count ≥10,000 μL with or without transfusion support
- Hemoglobin ≥8.0 g/dL with or without transfusion support
- Measurable disease with a lymph node or tumor mass >1.5 cm in at least one dimension as assessed by computed tomography (CT)
- ...
- Platelet count ≥10,000 μL with or without transfusion support
- Hemoglobin ≥8.0 g/dL with or without transfusion support
- Measurable disease with a lymph node or tumor mass >1.5 cm in at least one dimension as assessed by computed tomography (CT)
- Total bilirubin ≤1.5 x ULN
- Ability to voluntarily sign consent for and adhere to the entire study visit schedule and all protocol requirements
- Signed and dated institutional review board (IRB)/independent ethics committee (IEC)-approved informed consent form (ICF) before any study specific screening procedures are performed
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- For women of childbearing potential (WCBP): negative serum β-human chorionic gonadotropin (βhCG) pregnancy test within 1 week before first dose (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])
- Diagnosis of active CLL or SLL that meets at least 1 of the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria for requiring treatment
- Serum creatinine ≤2.0 x ULN
- Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≤3 x upper limit of normal (ULN)
- 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 duvelisib and for 12 months after last dose of ofatumumab. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception
- Received either IPI-145 or ofatumumab while participating in study IPI-145-07 and experienced radiologically-confirmed disease progression
Exclusion Criteria
- Pregnant or breastfeeding women
- Concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix, bladder, or prostate not requiring treatment. Subjects with previous malignancies are eligible provided that they have been disease-free for ≥2 years
- History of alcohol abuse or chronic liver disease (other than metastatic disease to the liver)
- ...
- Pregnant or breastfeeding women
- Concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix, bladder, or prostate not requiring treatment. Subjects with previous malignancies are eligible provided that they have been disease-free for ≥2 years
- History of alcohol abuse or chronic liver disease (other than metastatic disease to the liver)
- Use of any anticancer medication from documented PD on Study IPI-145-07 to enrollment (Note: corticosteroids to manage CLL/SLL-related symptoms are allowed)
- Prior, current, or chronic hepatitis B or hepatitis C infection
- History of Richter's transformation or prolymphocytic leukemia
- Known central nervous system (CNS) lymphoma or leukemia; subjects with symptoms of CNS disease must have a negative computed tomography (CT) scan or negative diagnostic lumbar puncture prior to first dose
- Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition), or any important medical illness or abnormal laboratory finding that would, in the Investigator's judgment, increase the subject's risk while participating in this study
- Baseline QT interval corrected with Fridericia's method (QTcF) >480 ms NOTE: this criterion does not apply to subjects with a right or left bundle branch block (BBB)
- Subjects to receive ofatumumab: hypersensitivity to ofatumumab or its excipients.
- Subjects to receive duvelisib: Administration of medications or foods that are strong inhibitors or inducers of cytochrome P450 (CYP) 3A within 2 weeks of starting duvelisib
- History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months
- Greater than 3 months from confirmed progressive disease on Study IPI-145-07
- Prior surgery or gastrointestinal dysfunction that may affect drug absorption (eg, gastric bypass surgery, gastrectomy)
- Autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenia purpura (ITP) that is uncontrolled or requires >20 mg daily (QD) of prednisone (or equivalent) to maintain hemoglobin >8.0 g/dL or platelets >10,000 μL without transfusion support
- Discontinued study participation in Verastem-sponsored IPI-145-07 study
- Unable to receive prophylactic treatment for pneumocystis and herpes simplex virus (HSV)
- Major surgery or invasive intervention within 4 weeks prior to first dose
- Human immunodeficiency virus (HIV) infection
- Ongoing systemic bacterial, fungal, or viral infections at the time of initiation of study treatment (defined as requiring 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 Screening and/or Cycle 1 Day 1 (predose))
Tracking Information
- NCT #
- NCT02049515
- Collaborators
- Not Provided
- Investigators
- Study Chair: Hagop Youssoufian, MD Verastem, Inc.
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