A Phase 3 Extension Study of Duvelisib and Ofatumumab in Participants With CLL/SLL Previously Enrolled in Study IPI-145-07

NCT ID: NCT02049515

Last Updated: 2023-09-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 99 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-31
• Study Completion Date: 2020-06-12

Brief Summary

A Phase 3 (extension) clinical trial to examine the efficacy of IPI-145 (duvelisib) monotherapy or ofatumumab monotherapy in participants with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who experienced disease progression after treatment with IPI-145 or ofatumumab in study IPI-145-07 (NCT02004522).

Detailed Description

The study was designed as an open-label, two-arm extension evaluation to enable participants who experienced radiologically confirmed disease progression in study IPI-145-07 to receive the alternative treatment (either IPI-145 or ofatumumab) other than what was received during study IPI-145-07.

Participants who previously had received ofatumumab in study IPI-145-07 received a starting dose of 25 milligrams (mg) IPI-145 twice daily 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 occurred first. After completing approximately 11 cycles of treatment with duvelisib, participants who, in the judgment of the investigator, may have derived benefit from continued treatment may have continued to receive additional cycles of duvelisib until disease progression or unacceptable toxicity. However, to receive additional cycles of duvelisib beyond 11 cycles, participants must have had evidence of response and CLL/SLL requiring treatment according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL)/International Working Group by Cycle 12 Day 1.

Participants who previously received IPI-145 in study IPI-145-07 received treatment consistent approved product labeling which consisted of a starting dose of 300 mg ofatumumab on Day 1, followed by seven weekly doses of 2000 mg. Thereafter, participants received 2000 mg ofatumumab once every month for four months unless disease progression or unacceptable toxicity occurred. Administration of ofatumumab was not to exceed the 12 doses (within 7 cycles).

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IPI-145

IPI-145 was administered orally and supplied as 5 mg and 25 mg formulated capsules.

Group Type: EXPERIMENTAL

IPI-145

Intervention Type: DRUG

PI3K Inhibitor

Ofatumumab

Ofatumumab was administered as an intravenous (IV) infusion and was supplied in single-use vials at two strengths, 100 mg/5 milliliters (mL) and 1000 mg/50 mL.

Group Type: ACTIVE_COMPARATOR

Ofatumumab

Intervention Type: DRUG

Monoclonal antibody

Interventions

IPI-145

PI3K Inhibitor

Intervention Type: DRUG

Ofatumumab

Monoclonal antibody

Intervention Type: DRUG

Other Intervention Names

Duvelisib; Copiktra; PI3K Inhibitor; Arzerra

Eligibility Criteria

Inclusion Criteria

• 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 met at least one of the IWCLL 2008 criteria for requiring treatment
• Measurable disease with a lymph node or tumor mass >1.5 centimeters in at least one dimension as assessed by computed tomography (CT)
• Eastern Cooperative Oncology Group performance status of 0-2
• Must have met the following laboratory parameters:

1. Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≤3 x upper limit of normal (ULN)

2. Total bilirubin ≤1.5 x ULN

3. Serum creatinine ≤2.0 x ULN

4. Hemoglobin ≥8.0 grams/deciliter (g/dL) with or without transfusion support

5. Platelet count ≥10,000 microliters (μL) with or without transfusion support

• For women of childbearing potential (WCBP): negative serum β-human chorionic gonadotropin pregnancy test within one week before first dose (WCBP defined as a sexually mature woman who had not undergone surgical sterilization or who had not been naturally post-menopausal for at least 24 consecutive months [women ≤55 years] or 12 consecutive months [women >55 years])
• Willingness of male and female participants who were 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 have used barrier contraception
• Ability to voluntarily sign consent for and adhere to the entire study visit schedule and all protocol requirements
• Signed and dated institutional review board/independent ethics committee-approved informed consent form before any study-specific screening procedures are performed

Exclusion Criteria

• Discontinued study participation in Verastem-sponsored IPI-145-07 study
• Greater than 3 months from confirmed progressive disease on Study IPI-145-07
• History of Richter's transformation or prolymphocytic leukemia
• Autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura that was uncontrolled or requires >20 mg daily 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; participants with symptoms of CNS disease must have had a negative CT scan or negative diagnostic lumbar puncture prior to first dose
• Use of any anticancer medication from documented progressive disease on Study IPI-145-07 to enrollment (Note: corticosteroids to manage CLL/SLL-related symptoms were allowed)
• Human immunodeficiency virus infection
• Prior, current, or chronic hepatitis B or hepatitis C infection
• History of alcohol abuse or chronic liver disease (other than metastatic disease to the liver)
• Unable to receive prophylactic treatment for pneumocystis and herpes simplex virus
• Baseline QT interval corrected with Fridericia's method >480 milliseconds Note: this criterion did not apply to participants with a right or left bundle branch block
• Concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix, bladder, or prostate not requiring treatment. Participants with previous malignancies were eligible provided that they had been disease-free for ≥2 years
• History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months
• Unstable or severe uncontrolled medical condition (for example, unstable cardiac function, unstable pulmonary condition), or any important medical illness or abnormal laboratory finding that would, in the investigator's judgment, have increased the participant's risk while participating in this study
• Prior surgery or gastrointestinal dysfunction that may have affected drug absorption (for example, gastric bypass surgery, gastrectomy)
• Participants to receive duvelisib: Administration of medications or foods that were strong inhibitors or inducers of cytochrome P450 3A within 2 weeks of starting duvelisib
• Major surgery or invasive intervention within 4 weeks prior to first dose
• Pregnant or breastfeeding women
• Participants to receive ofatumumab: hypersensitivity to ofatumumab or its excipients.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

SecuraBio

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hagop Youssoufian, MD

Role: STUDY_CHAIR

Verastem, Inc.

Locations

La Jolla, California, United States

Denver, Colorado, United States

Fort Myers, Florida, United States

St. Petersburg, Florida, United States

Boston, Massachusetts, United States

Boston, Massachusetts, United States

St Louis, Missouri, United States

Hackensack, New Jersey, United States

New Brunswick, New Jersey, United States

New York, New York, United States

New York, New York, United States

Cincinnati, Ohio, United States

Nashville, Tennessee, United States

Charlottesville, Virginia, United States

Bedford Park, , Australia

East Melbourne, , Australia

Melbourne, , Australia

Linz, , Austria

Vienna, , Austria

Vienna, , Austria

Wels, , Austria

Brussels, , Belgium

Brussels, , Belgium

Ghent, , Belgium

Leuven, , Belgium

Sint-Niklaas, , Belgium

Argenteuil, , France

Bobigny, , France

Bordeaux, , France

Caen, , France

Clermont-Ferrand, , France

La Roche-sur-Yon, , France

Limoges, , France

Nantes, , France

Rennes, , France

Vandœuvre-lès-Nancy, , France

Berlin, , Germany

Leer, , Germany

Ulm, , Germany

Budapest, , Hungary

Budapest, , Hungary

Debrecen, , Hungary

Győr, , Hungary

Kaposvár, , Hungary

Pécs, , Hungary

Szeged, , Hungary

Catania, , Italy

Lecce, , Italy

Meldola, , Italy

Milan, , Italy

Milan, , Italy

Padua, , Italy

Ravenna, , Italy

Rimini, , Italy

Roma, , Italy

Auckland, , New Zealand

Palmerston North, , New Zealand

Barcelona, , Spain

Barcelona, , Spain

Barcelona, , Spain

Madrid, , Spain

Madrid, , Spain

Pamplona, , Spain

Bournemouth, , United Kingdom

Leeds, , United Kingdom

Manchester, , United Kingdom

Nottingham, , United Kingdom

Oxford, , United Kingdom

Sutton, , United Kingdom

Countries

United States; Australia; Austria; Belgium; France; Germany; Hungary; Italy; New Zealand; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2013-003639-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IPI-145-12

Identifier Type: -

Identifier Source: org_study_id