A Phase 1b/2 Study of IPI-145 Plus FCR in Previously Untreated, Younger Patients With CLL

NCT02158091 | Active Not Recruiting Phase 1 Results DMC

• 1 other identifier: 14-193
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is evaluating a new drug called IPI-145 in combination with the standard drugs fludarabine, cyclophosphamide, and rituximab (FCR), as a possible treatment for chronic lymphocytic leukemia (CLL).

Conditions

Chronic Lymphocytic Leukemia

Keywords

Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (2)

• Number of Patients Who Experienced a Dose Limiting Toxicity (DLT) During Phase I

  To assess the safety of IPI145 in combination with FCR in previously untreated younger patients with CLL. DLT is based on the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. DLT refers to toxicities experienced at any time during the study treatment, defined as Grade 3 or greater hematologic toxicity (except Grade 3 or Grade 4 neutropenia or thrombocytopenia that lasts less than or equal to 10 days off treatment), any Grade 3 or greater non-hematologic toxicity (except Grade 3 or greater nausea, vomiting, diarrhea, Grade 3 infusion reactions), Grade 3 asymptomatic laboratory abnormalities that improve to grade 2 or less within 3 days, Inability to receive day 1 therapy of Cycle 2 even after a three week treatment delay due to drug related toxicity from prior cycle, and any Grade 4 or greater elevation in AST ALT values

  . Participants were assessed every week or more often as needed during Cycle 1, and every Day 1 Cycles 2 and onward-Dose-limiting toxicities (DLTs) occurring during the first cycle of treatment will be used in determining the Phase II MTD/RP2D

• Number of Patients Who Had a Minimal Residual Disease (MRD) Negative Complete Response (CR) 2 Months After Chemotherapy

  To determine the rate of minimal residual disease negative complete response (MRD negative CR) in the bone marrow at 2 months post last cycle of FCR, participants will have a bone marrow biopsy procedure 2 months after completing combination therapy (IPI-145+ FCR) in tandem with a chest,neck, abdomen and pelvic PET CT scan. A central read of the PET CT scan will confirm a radiographic complete response, and the bone marrow pathology and morphology assessments will confirm morphological CR in the bone marrow, while MRD testing will be done by four-color flow cytometry on the bone marrow aspirate with a detection level of 10-4. This will include all patients treated and evaluable at maximum tolerated dose, and at the recommended phase II dose ( RP2D)

  2 months after completion of combination therapy of IPI-145 and FCR

Secondary Outcomes (9)

• Overall Response Rate

  At baseline, End of Cycle 3, and 2 months post FCR

• Number of Participants With Serious and Non-Serious Adverse Events

  Up to 210 days

• Rate of Minimal Residual Disease (MRD) in the Peripheral Blood

  2 Years

• Rate of Treatment Related Adverse Effects

  210 days

• Determine the Association of Established CLL Prognostic Factors With Clinical Response

  2 Years

Study Arms (1)

IPI-145

EXPERIMENTAL

Phase I-Dose escalation will occur using a standard 3-3 dose escalation beginning in dose level 1 with dose cohorts and escalation. * Each treatment cycle lasts 28 days (except cycle 1, which is 35 days) during which time IPI-145 will be taken twice daily. The study begins with 1 week of IPI-145 monotherapy. * Fludarabine, cyclophosphamide, rituximab (iFCR) - FCR will subsequently be introduced after 1 week and administered at standard dosing for up to 6 cycles, with dose reductions permitted. IPI-145 will be continued through the course of chemotherapy and for up to 2 years maintenance after completing chemotherapy Phase II - 20 additional patients treated with IPI-145 at the Recommended Phase II Dose (RP2D) + fludarabine, cyclophosphamide, rituximab (FCR) with standard dosing.

Drug: IPI-145; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Rituximab

Interventions

IPI-145 DRUG

oral PI3K delta/gamma inhibitor

IPI-145

Fludarabine DRUG

intravenous chemotherapy

Also known as: Fludara

IPI-145

Cyclophosphamide DRUG

intravenous chemotherapy

Also known as: Cytoxan®, Neosar®

IPI-145

Rituximab DRUG

intravenous immunotherapy

Also known as: Rituxan

IPI-145

Eligibility Criteria

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

You may qualify if:

• confirmed diagnosis of CLL and an indication for treatment as per IW-CLL 2008 criteria
• no prior therapy for CLL
• age 18-65 -- ECOG performance status ≤1

You may not qualify if:

• May not be receiving any other study agents
• Known CNS involvement
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because IPI-145 has the potential for teratogenic or abortifacient effects.
• Individuals with a history of a different malignancy are ineligible except for the following circumstances. disease-free for at least 5 years and deemed to be at low risk for recurrence. Individuals with the following cancers are eligible if diagnosed and treated with curative intent within the past 5 years: cervical cancer in situ, localized prostate cancer, and basal cell or squamous cell carcinoma of the skin
• HIV-positive individuals, because of the potential for pharmacokinetic interactions with IPI-145
• Inadequate hepatic function defined by aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \>2.5 x upper limit of normal (ULN); direct bilirubin \>1.5 x ULN, unless due to hemolysis or Gilbert's syndrome
• Inadequate renal function defined by serum creatinine \>1.5 x ULN.
• Baseline QTcF \>480 ms. NOTE: This criterion does not apply to patients with a left bundle branch block
• Concurrent treatment with any agent known to prolong the QTc interval
• Patients with a history of active tuberculosis within the preceding two years.
• Patients who have had a venous thromboembolic event (e.g., PE/DVT) requiring anticoagulation and who meet any of the following criteria:
• Have been on a stable dose of anticoagulation for \<1 month
• Have had a Grade 2, 3 or 4 hemorrhage in the last 30 days
• Are experiencing continued symptoms from their event

Sponsors & Collaborators

• Secura Bio, Inc.: collaborator
• Dana-Farber Cancer Institute: lead

Study Sites (2)

Beth Isreal Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

duvelisib; fludarabine; fludarabine phosphate; Cyclophosphamide; Rituximab

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Matthew Davids, MD
• Organization: Dana-Farber Cancer Institute

matthew_davids@dfci.harvard.edu

617-632-6331

Study Officials

• Matthew Davids, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 4, 2014
• First Posted: June 6, 2014
• Study Start: June 27, 2014
• Primary Completion: October 1, 2017
• Study Completion (Estimated): July 1, 2026
• Last Updated: February 13, 2026
• Results First Posted: December 11, 2018

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)