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

NCT02049515 | Completed Phase 3 Results

• 2 other identifiers: IPI-145-122013-003639-31
• Study Type: interventional
• Target: 99
• Locations: 10 countries
• Sites: 66

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).

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Keywords

Phase 3; CLL/SLL; PI3K

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  ORR was defined as the percentage of participants with a best response (per investigator assessment) of complete response (CR), CR with incomplete marrow recovery (CRi), partial response (PR), or PR with lymphocytosis (PRwL), according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) or revised International Working Group Response (IWG) Criteria, with modification for treatment-related lymphocytosis. The 95% confidence interval was calculated using exact binomial method. Select IWCLL criteria for tumor load assessed by computed tomography (CT): CR/CRi (CLL only), lymphadenopathy (none \>1.5 centimeters \[cm\]), hepatomegaly/splenomegaly (none); PR, lymphadenopathy/hepatomegaly/splenomegaly (decrease ≥50%); PRwL, lymphadenopathy only (decrease ≥50%). Select IWG criteria for tumor load assessed by CT: CR, lymphadenopathy/hepatomegaly/splenomegaly (normal size); PR, lymphadenopathy/hepatomegaly/splenomegaly (decrease ≥50%); PRwL, lymphadenopathy only (decrease ≥50%).

  Until progressive disease (PD), death, or other anticancer therapy is initiated (up to 4.5 years)

Secondary Outcomes (2)

• Duration of Response (DOR)

  From the first documentation of response to the first documentation of PD or death due to any cause (up to 4.5 years)

• Progression-free Survival (PFS)

  From the first dose of study treatment to the first documentation of PD or death from any cause (up to 4.5 years)

Study Arms (2)

IPI-145

EXPERIMENTAL

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

Drug: IPI-145

Ofatumumab

ACTIVE COMPARATOR

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.

Drug: Ofatumumab

Interventions

IPI-145 DRUG

PI3K Inhibitor

Also known as: Duvelisib, Copiktra, PI3K Inhibitor

IPI-145

Ofatumumab DRUG

Monoclonal antibody

Also known as: Arzerra

Ofatumumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≤3 x upper limit of normal (ULN)
• Total bilirubin ≤1.5 x ULN
• Serum creatinine ≤2.0 x ULN
• Hemoglobin ≥8.0 grams/deciliter (g/dL) with or without transfusion support
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• SecuraBio: lead

Study Sites (69)

Unknown Facility

La Jolla, California, 92093-0698, United States

Location

Unknown Facility

Denver, Colorado, 80218, United States

Location

Unknown Facility

Fort Myers, Florida, 33916, United States

Location

Unknown Facility

St. Petersburg, Florida, 33705, United States

Location

Unknown Facility

Boston, Massachusetts, 02114, United States

Location

Unknown Facility

Boston, Massachusetts, 02115, United States

Location

Unknown Facility

St Louis, Missouri, 63130, United States

Location

Unknown Facility

Hackensack, New Jersey, 07601, United States

Location

Unknown Facility

New Brunswick, New Jersey, 08903, United States

Location

Unknown Facility

New York, New York, 10032, United States

Location

Unknown Facility

New York, New York, 10065, United States

Location

Unknown Facility

Cincinnati, Ohio, 45236, United States

Location

Unknown Facility

Nashville, Tennessee, 37203, United States

Location

Unknown Facility

Charlottesville, Virginia, 22903, United States

Location

Unknown Facility

Bedford Park, 5042, Australia

Location

Unknown Facility

East Melbourne, 3002, Australia

Location

Unknown Facility

Melbourne, 3058, Australia

Location

Unknown Facility

Linz, 4010, Austria

Location

Unknown Facility

Vienna, 1090, Austria

Location

Unknown Facility

Vienna, 1130, Austria

Location

Unknown Facility

Wels, 4600, Austria

Location

Unknown Facility

Brussels, 1000, Belgium

Location

Unknown Facility

Brussels, 1200, Belgium

Location

Unknown Facility

Ghent, 9000, Belgium

Location

Unknown Facility

Leuven, 3000, Belgium

Location

Unknown Facility

Sint-Niklaas, 9100, Belgium

Location

Unknown Facility

Argenteuil, 95107, France

Location

Unknown Facility

Bobigny, 93009, France

Location

Unknown Facility

Bordeaux, 33076, France

Location

Unknown Facility

Caen, 14033, France

Location

Unknown Facility

Clermont-Ferrand, 63100, France

Location

Unknown Facility

La Roche-sur-Yon, 85025, France

Location

Unknown Facility

Limoges, 87042, France

Location

Unknown Facility

Nantes, 44000, France

Location

Unknown Facility

Rennes, 35033, France

Location

Unknown Facility

Vandœuvre-lès-Nancy, 54511, France

Location

Unknown Facility

Berlin, 10707, Germany

Location

Unknown Facility

Leer, 26789, Germany

Location

Unknown Facility

Ulm, 89081, Germany

Location

Unknown Facility

Budapest, 1083, Hungary

Location

Unknown Facility

Budapest, 1122, Hungary

Location

Unknown Facility

Debrecen, 4032, Hungary

Location

Unknown Facility

Győr, 9024, Hungary

Location

Unknown Facility

Kaposvár, 7400, Hungary

Location

Unknown Facility

Pécs, 7624, Hungary

Location

Unknown Facility

Szeged, 6725, Hungary

Location

Unknown Facility

Catania, 95124, Italy

Location

Unknown Facility

Lecce, 73100, Italy

Location

Unknown Facility

Meldola, 47014, Italy

Location

Unknown Facility

Milan, 20132, Italy

Location

Unknown Facility

Milan, 20162, Italy

Location

Unknown Facility

Padua, 35128, Italy

Location

Unknown Facility

Ravenna, 48121, Italy

Location

Unknown Facility

Rimini, 47923, Italy

Location

Unknown Facility

Roma, 00133, Italy

Location

Unknown Facility

Auckland, 1023, New Zealand

Location

Unknown Facility

Palmerston North, 4442, New Zealand

Location

Unknown Facility

Barcelona, 08035, Spain

Location

Unknown Facility

Barcelona, 08036, Spain

Location

Unknown Facility

Barcelona, 08041, Spain

Location

Unknown Facility

Madrid, 28033, Spain

Location

Unknown Facility

Madrid, 28050, Spain

Location

Unknown Facility

Pamplona, 31008, Spain

Location

Unknown Facility

Bournemouth, BH7 7DW, United Kingdom

Location

Unknown Facility

Leeds, LS9 7TF, United Kingdom

Location

Unknown Facility

Manchester, M20 4BX, United Kingdom

Location

Unknown Facility

Nottingham, NG5 1PB, United Kingdom

Location

Unknown Facility

Oxford, OX3 7JL, United Kingdom

Location

Unknown Facility

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

duvelisib; ofatumumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Beth Gregory, PharmD, MBA
• Organization: Secura Bio, Inc.

bgregory@securabio.com

1-702-254-0011

Study Officials

• Hagop Youssoufian, MD

  Verastem, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2014
• First Posted: January 30, 2014
• Study Start: December 1, 2013
• Primary Completion: June 12, 2020
• Study Completion: June 12, 2020
• Last Updated: September 21, 2023
• Results First Posted: February 21, 2023

Record last verified: 2023-09

Locations

DE (3); AU (4); NZ (2); HU (7); ES (6); BE (5); IT (9); GB (6); US (14); FR (10)