Recruitment

Recruitment Status
Completed
Estimated Enrollment
150

Inclusion Criteria

Signed and dated institutional review board (IRB)/independent ethics committee (IEC)-approved informed consent form (ICF) before any study specific screening procedures are performed
Measurable disease with a lymph node or tumor mass >1.5 cm in at least one dimension as assessed by computed tomography (CT)
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
...
Signed and dated institutional review board (IRB)/independent ethics committee (IEC)-approved informed consent form (ICF) before any study specific screening procedures are performed
Measurable disease with a lymph node or tumor mass >1.5 cm in at least one dimension as assessed by computed tomography (CT)
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
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Received either IPI-145 or ofatumumab while participating in study IPI-145-07 and experienced radiologically-confirmed disease progression
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
Hemoglobin ≥8.0 g/dL with or without transfusion support
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])
Serum creatinine ≤2.0 x ULN
Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≤3 x upper limit of normal (ULN)
Ability to voluntarily sign consent for and adhere to the entire study visit schedule and all protocol requirements
Total bilirubin ≤1.5 x ULN
Platelet count ≥10,000 μL with or without transfusion support

Exclusion Criteria

History of alcohol abuse or chronic liver disease (other than metastatic disease to the liver)
Discontinued study participation in Verastem-sponsored IPI-145-07 study
Subjects to receive ofatumumab: hypersensitivity to ofatumumab or its excipients.
...
History of alcohol abuse or chronic liver disease (other than metastatic disease to the liver)
Discontinued study participation in Verastem-sponsored IPI-145-07 study
Subjects to receive ofatumumab: hypersensitivity to ofatumumab or its excipients.
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))
Human immunodeficiency virus (HIV) infection
Unable to receive prophylactic treatment for pneumocystis and herpes simplex virus (HSV)
History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months
Pregnant or breastfeeding women
Major surgery or invasive intervention within 4 weeks prior to first dose
Greater than 3 months from confirmed progressive disease on Study IPI-145-07
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
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)
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
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
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
Prior surgery or gastrointestinal dysfunction that may affect drug absorption (eg, gastric bypass surgery, gastrectomy)
History of Richter's transformation or prolymphocytic leukemia
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
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

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

Signed and dated institutional review board (IRB)/independent ethics committee (IEC)-approved informed consent form (ICF) before any study specific screening procedures are performed
Measurable disease with a lymph node or tumor mass >1.5 cm in at least one dimension as assessed by computed tomography (CT)
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
...
Signed and dated institutional review board (IRB)/independent ethics committee (IEC)-approved informed consent form (ICF) before any study specific screening procedures are performed
Measurable disease with a lymph node or tumor mass >1.5 cm in at least one dimension as assessed by computed tomography (CT)
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
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Received either IPI-145 or ofatumumab while participating in study IPI-145-07 and experienced radiologically-confirmed disease progression
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
Hemoglobin ≥8.0 g/dL with or without transfusion support
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])
Serum creatinine ≤2.0 x ULN
Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≤3 x upper limit of normal (ULN)
Ability to voluntarily sign consent for and adhere to the entire study visit schedule and all protocol requirements
Total bilirubin ≤1.5 x ULN
Platelet count ≥10,000 μL with or without transfusion support

Exclusion Criteria

History of alcohol abuse or chronic liver disease (other than metastatic disease to the liver)
Discontinued study participation in Verastem-sponsored IPI-145-07 study
Subjects to receive ofatumumab: hypersensitivity to ofatumumab or its excipients.
...
History of alcohol abuse or chronic liver disease (other than metastatic disease to the liver)
Discontinued study participation in Verastem-sponsored IPI-145-07 study
Subjects to receive ofatumumab: hypersensitivity to ofatumumab or its excipients.
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))
Human immunodeficiency virus (HIV) infection
Unable to receive prophylactic treatment for pneumocystis and herpes simplex virus (HSV)
History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months
Pregnant or breastfeeding women
Major surgery or invasive intervention within 4 weeks prior to first dose
Greater than 3 months from confirmed progressive disease on Study IPI-145-07
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
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)
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
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
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
Prior surgery or gastrointestinal dysfunction that may affect drug absorption (eg, gastric bypass surgery, gastrectomy)
History of Richter's transformation or prolymphocytic leukemia
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
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

Tracking Information

NCT #
NCT02049515
Collaborators
Not Provided
Investigators
Study Chair: Hagop Youssoufian, MD Verastem, Inc.