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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02158091
Recruitment Status : Active, not recruiting
First Posted : June 6, 2014
Last Update Posted : December 20, 2017
Verastem, Inc.
Information provided by (Responsible Party):
Matthew S. Davids, MD, Dana-Farber Cancer Institute

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).

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Drug: IPI-145 Drug: Fludarabine Drug: Cyclophosphamide Drug: Rituximab Phase 1 Phase 2

Detailed Description:

Patients who fulfill eligibility criteria will be entered into the trial to receive IPI-145 in combination with the standard drugs fludarabine, cyclophosphamide, and rituximab (FCR). After the screening procedures confirm participation in the research study:

Phase I

The investigators are looking for the highest dose of the combination of study drugs that can be administered safely without severe or unmanageable side effects in participants that have CLL. Not everyone who participates in this research study will receive the same dose of the study drug. The dose given will depend on the number of participants who have been enrolled in the study prior and how well the dose was tolerated.

Phase II:

Patients treated with IPI-145 at the Recommended Phase II Dose (RP2D) + fludarabine, cyclophosphamide, rituximab (FCR) with standard dosing.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Study of IPI-145 in Combination With Fludarabine, Cyclophosphamide, and Rituximab (iFCR) in Previously Untreated, Younger Patients With Chronic Lymphocytic Leukemia.
Study Start Date : July 2014
Actual Primary Completion Date : October 2017
Estimated Study Completion Date : July 2021

Arm Intervention/treatment
Experimental: IPI-145

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
oral PI3K delta/gamma inhibitor

Drug: Fludarabine
intravenous chemotherapy
Other Name: Fludara

Drug: Cyclophosphamide
intravenous chemotherapy
Other Names:
  • Cytoxan®
  • Neosar®

Drug: Rituximab
intravenous immunotherapy
Other Name: Rituxan

Primary Outcome Measures :
  1. Rate of minimal residual disease negative complete response (MRD-negative CR) in the bone marrow [ Time Frame: 2 months post chemotherapy ]
    Rate of minimal residual disease negative complete response (MRD-negative CR) in the bone marrow at 2 months post last cycle of FCR

  2. Determination of the maximum tolerated dose (MTD) of IPI-145 with FCR [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Duration of Response [ Time Frame: Baseline, 35 weeks ]
    2008 IW-CLL criteria

  2. Number of Participants with Serious and Non-Serious Adverse Events [ Time Frame: Up to 210 days ]
    Toxicity assessments will be done using the CTEP Version 4.0 of the NCI Common Terminology Criteria for Adverse Events (CTCAE)

  3. Overall Response Rate [ Time Frame: 2 Years ]
    2008 IW-CLL criteria

  4. Complete response rate [ Time Frame: 2 Years ]
    2008 IW-CLL criteria

  5. Partial response rate [ Time Frame: 2 Years ]
    2008 IW-CLL criteria

  6. Rate of minimal residual disease (MRD) in the peripheral blood [ Time Frame: 2 Years ]
  7. Established CLL prognostic factors [ Time Frame: 2 Years ]
    Fisher's exact test for categorical variables and Wilcoxon's rank sum test

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • History of alcohol abuse, chronic hepatitis, or other chronic liver disease (other than direct CLL liver involvement)
  • Foods or medications that are strong or moderate inhibitors or inducers of CYP3A taken within 1 week prior to study treatment and for the duration of the study
  • Unable to receive prophylactic treatment for pneumocystis

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02158091

United States, Massachusetts
Beth Isreal Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Dana-Farber Cancer Institute
Verastem, Inc.
Principal Investigator: Matthew Davids, MD Dana-Farber Cancer Institute

Responsible Party: Matthew S. Davids, MD, Principal Investigator, Dana-Farber Cancer Institute Identifier: NCT02158091     History of Changes
Other Study ID Numbers: 14-193
First Posted: June 6, 2014    Key Record Dates
Last Update Posted: December 20, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Matthew S. Davids, MD, Dana-Farber Cancer Institute:
Chronic Lymphocytic Leukemia

Additional relevant MeSH terms:
Fludarabine phosphate
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antiviral Agents
Anti-Infective Agents