A Phase 1b/2 Study of IPI-145 Plus FCR in Previously Untreated, Younger Patients With CLL
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|ClinicalTrials.gov Identifier: NCT02158091|
Recruitment Status : Active, not recruiting
First Posted : June 6, 2014
Results First Posted : December 11, 2018
Last Update Posted : December 11, 2018
|Condition or disease||Intervention/treatment||Phase|
|Chronic Lymphocytic Leukemia||Drug: IPI-145 Drug: Fludarabine Drug: Cyclophosphamide Drug: Rituximab||Phase 1 Phase 2|
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:
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.
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)|
|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.|
|Actual Study Start Date :||June 27, 2014|
|Actual Primary Completion Date :||October 2017|
|Estimated Study Completion Date :||July 2021|
Phase I-Dose escalation will occur using a standard 3-3 dose escalation beginning in dose level 1 with dose cohorts and escalation.
oral PI3K delta/gamma inhibitor
Other Name: Fludara
Other Name: Rituxan
- Number of Patients Who Experienced a Dose Limiting Toxicity (DLT) During Phase I [ Time Frame: . 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 ]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
- Number of Patients Who Had a Minimal Residual Disease (MRD) Negative Complete Response (CR) 2 Months After Chemotherapy [ Time Frame: 2 months after completion of combination therapy of IPI-145 and FCR ]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)
- Overall Response Rate [ Time Frame: At baseline, End of Cycle 3, and 2 months post FCR ]Response and progression will be evaluated in this study using the 2008 IW-CLL criteria for CLL (Hallek et al., 2008)
- 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) and will include all participants who have received at least 1 dose of IPI-145. Toxicities will be assessed at minimum every week during cycle 1, on Day 1 of every cycle during Cycle 2 onward, and every other cycle Day 1 during maintenance.
- Rate of Minimal Residual Disease (MRD) in the Peripheral Blood [ Time Frame: 2 Years ]Participants will have MRD testing in the peripheral blood by four-color flow cytometry at the end of cycle 3, 2 months post combination therapy, and every 6 months thereafter for the duration of treatment and subsequent follow up
- Rate of Treatment Related Adverse Effects [ Time Frame: 210 days ]Participants will be evaluable for this endpoint if they have had at least 1 dose of study treatment. Toxicities will be assessed at minimum each week during cycle 1, and each day 1 during combination therapy, and then every two months thereafter. CTCAE version 4.0 will be used to assess toxicity term and grading.
- Determine the Association of Established CLL Prognostic Factors With Clinical Response [ Time Frame: 2 Years ]Fisher's exact test for categorical variables and Wilcoxon's rank sum test will be used-
- Rate of Complete Response and Partial Response [ Time Frame: At baseline, End of Cycle 3, and 2 months post FCR and then per investigator discretion thereafter ]Response and progression will be evaluated in this study using the 2008 IW-CLL criteria for CLL (Hallek et al., 2008)
- Rate of Progression Free Survival [ Time Frame: At baseline, End of Cycle 3, and 2 months post FCR and then per investigator discretion thereafter ]2008 IW-CLL criteria
- Event Free Survival Rate [ Time Frame: At baseline, End of Cycle 3, and 2 months post FCR and then per investigator discretion thereafter ]Response and progression will be evaluated in this study using the 2008 IW-CLL criteria for CLL (Hallek et al., 2008)
- Duration of Remission Rate [ Time Frame: At baseline, End of Cycle 3, and 2 months post FCR and then per investigator discretion thereafter ]Response and progression will be evaluated in this study using the 2008 IW-CLL criteria for CLL (Hallek et al., 2008)Frequency of follow up visits and scans are per MD discretion. Recommended follow up visits for a minimum of one year
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 ClinicalTrials.gov 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|
|Principal Investigator:||Matthew Davids, MD||Dana-Farber Cancer Institute|