Recruitment

Recruitment Status
Completed
Estimated Enrollment
150

Inclusion Criteria

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])
Ability to voluntarily sign consent for and adhere to the entire study visit schedule and all protocol requirements
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])
Ability to voluntarily sign consent for and adhere to the entire study visit schedule and all protocol requirements
Hemoglobin ≥8.0 g/dL with or without transfusion support
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
Platelet count ≥10,000 μL with or without transfusion support
Serum creatinine ≤2.0 x ULN
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
Total bilirubin ≤1.5 x ULN
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
Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≤3 x upper limit of normal (ULN)
Measurable disease with a lymph node or tumor mass >1.5 cm in at least one dimension as assessed by computed tomography (CT)

Exclusion Criteria

Human immunodeficiency virus (HIV) infection
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)
Pregnant or breastfeeding women
...
Human immunodeficiency virus (HIV) infection
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)
Pregnant or breastfeeding women
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
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
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
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
Prior surgery or gastrointestinal dysfunction that may affect drug absorption (eg, gastric bypass surgery, gastrectomy)
Major surgery or invasive intervention within 4 weeks prior to first dose
Prior, current, or chronic hepatitis B or hepatitis C 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
History of alcohol abuse or chronic liver disease (other than metastatic disease to the liver)
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
Discontinued study participation in Verastem-sponsored IPI-145-07 study
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))
Subjects to receive ofatumumab: hypersensitivity to ofatumumab or its excipients.
History of Richter's transformation or prolymphocytic leukemia
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)
Greater than 3 months from confirmed progressive disease on Study IPI-145-07

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

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])
Ability to voluntarily sign consent for and adhere to the entire study visit schedule and all protocol requirements
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])
Ability to voluntarily sign consent for and adhere to the entire study visit schedule and all protocol requirements
Hemoglobin ≥8.0 g/dL with or without transfusion support
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
Platelet count ≥10,000 μL with or without transfusion support
Serum creatinine ≤2.0 x ULN
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
Total bilirubin ≤1.5 x ULN
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
Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≤3 x upper limit of normal (ULN)
Measurable disease with a lymph node or tumor mass >1.5 cm in at least one dimension as assessed by computed tomography (CT)

Exclusion Criteria

Human immunodeficiency virus (HIV) infection
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)
Pregnant or breastfeeding women
...
Human immunodeficiency virus (HIV) infection
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)
Pregnant or breastfeeding women
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
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
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
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
Prior surgery or gastrointestinal dysfunction that may affect drug absorption (eg, gastric bypass surgery, gastrectomy)
Major surgery or invasive intervention within 4 weeks prior to first dose
Prior, current, or chronic hepatitis B or hepatitis C 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
History of alcohol abuse or chronic liver disease (other than metastatic disease to the liver)
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
Discontinued study participation in Verastem-sponsored IPI-145-07 study
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))
Subjects to receive ofatumumab: hypersensitivity to ofatumumab or its excipients.
History of Richter's transformation or prolymphocytic leukemia
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)
Greater than 3 months from confirmed progressive disease on Study IPI-145-07

Locations

Nottingham, NG5 1PB
Limoges Cedex, 87042
Saint Petersburg, Florida, 33705
Ravenna, 48121
Roma, 00133
...
Nottingham, NG5 1PB
Limoges Cedex, 87042
Saint Petersburg, Florida, 33705
Ravenna, 48121
Roma, 00133
Leer, 26789
Boston, Massachusetts, 02114
Fort Myers, Florida, 33916
Barcelona, 08036
Nashville, Tennessee, 37203
New York, New York, 10065
Berlin, 10707
Bordeaux, 33076
Leeds, LS9 7TF
Bruxelles, 1000
Wien, 1130
Barcelona, 08041
Nantes, 44000
Pecs, 7624
La Roche Sur Yon, 85025
Rennes, 35033
Padova, 35128
Melbourne, 3058
Manchester, M20 4BX
Auckland, 1023
Rimini, 47923
Caen, 14033
Oxford, OX3 7JL
Pamplona, 31008
La Jolla, California, 92093-0698
New York, New York, 10032
Bedford Park, 5042
Cincinnati, Ohio, 45236
New Brunswick, New Jersey, 08903
Vienna, 1090
Leuven, 3000
Kaposvár, 7400
Gyor, 9024
Barcelona, 08035
Clermont Ferrand, 63100
Argenteuil Cedex, 95107
Hackensack, New Jersey, 07601
Saint Louis, Missouri, 63130
East Melbourne, 3002
Wels, 4600
Boston, Massachusetts, 02115
Denver, Colorado, 80218
Sutton, SM2 5PT
Szeged, 6725
Meldola, 47014
Vandœuvre-lès-Nancy, 54511
Charlottesville, Virginia, 22903
Lecce, 73100
Bobigny, 93009
Gent, 9000
Bournemouth, BH7 7DW
Milano, 20132
Catania, 95124
Debrecen, 4032
Milano, 20162
Madrid, 28050
Madrid, 28033
Ulm, 89081
Budapest, 1122
Palmerston North, 4442
Linz, 4010
Sint-Niklaas, 9100
Budapest, 1083
Bruxelles, 1200

Tracking Information

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