Clinical trial NCT02158091: A Phase 1b/2 Study of IPI-145 Plus FCR in Previously Untreated, Younger Patients With CLL
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 type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Chronic Lymphocytic Leukemia
Keywords: Chronic Lymphocytic Leukemia
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Secura Bio, Inc.
First posted: 2014-06-06
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Patients Who Experienced a Dose Limiting Toxicity (DLT) During Phase I
timeFrame: . 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
measure: Number of Patients Who Had a Minimal Residual Disease (MRD) Negative Complete Response (CR) 2 Months After Chemotherapy
timeFrame: 2 months after completion of combination therapy of IPI-145 and FCR
Secondary outcomes:
measure: Overall Response Rate
timeFrame: At baseline, End of Cycle 3, and 2 months post FCR
measure: Number of Participants With Serious and Non-Serious Adverse Events
timeFrame: Up to 210 days
measure: Rate of Minimal Residual Disease (MRD) in the Peripheral Blood
timeFrame: 2 Years
measure: Rate of Treatment Related Adverse Effects
timeFrame: 210 days
measure: Determine the Association of Established CLL Prognostic Factors With Clinical Response
timeFrame: 2 Years
measure: Rate of Complete Response and Partial Response
timeFrame: At baseline, End of Cycle 3, and 2 months post FCR and then per investigator discretion thereafter
measure: Rate of Progression Free Survival
timeFrame: At baseline, End of Cycle 3, and 2 months post FCR and then per investigator discretion thereafter
measure: Event Free Survival Rate
timeFrame: At baseline, End of Cycle 3, and 2 months post FCR and then per investigator discretion thereafter
measure: Duration of Remission Rate
timeFrame: At baseline, End of Cycle 3, and 2 months post FCR and then per investigator discretion thereafter
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Isreal Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Matthew Davids, MD
role: PRINCIPAL_INVESTIGATOR
References: