Clinical trial NCT02518113: A Study of LY3039478 in Combination With Dexamethasone in Participants With T-ALL/T-LBL
Official title: A Phase 1b/Randomized Phase 2 Study to Evaluate LY3039478 in Combination With Dexamethasone in T-ALL/T-LBL Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: T-cell Acute Lymphoblastic Leukemia
T-cell Lymphoblastic Lymphoma
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2015-08-07
Enrollment: 36
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to evaluate the safety of the study drug known as LY3039478 in combination with dexamethasone in participants with T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma (T-ALL/T-LBL).


Eligibility criteria: Inclusion Criteria:

* Have acute T-cell lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LBL).
* T-ALL or T-LBL participants with relapsed/refractory disease.
* Have had at least 60 days between prior hematopoietic stem cell transplantation (SCT) and first dose of study drug.
* Have a performance status of 0 to 2 on the Eastern Cooperative Oncology Group (ECOG) scale for adults.
* Lansky score \>50% for participants \<16 years old.
* Have adequate organ function.
* Are at least:

  * adult Phase 1 Part A and Phase 2: ≥16 years old at the time of screening
  * pediatric Phase 1 Part B: 2 to \<16 years old
* Men and women with reproductive potential: Must agree to use a reliable method of birth control during the study and for 3 months following the last dose of study drug(s) or country requirements, whichever is longer.
* Females with childbearing potential: Have had a negative serum pregnancy test ≤7 days before the first dose of study drug and also must not be breastfeeding.
* Are able to swallow capsules and tablets.

Exclusion Criteria:

* Have previously completed or withdrawn from this study or any other study investigating LY3039478 or other Notch inhibitors.
* Have evidence of uncontrolled, active infection \<7 days prior to administration of study medication.
* Have current or recent gastrointestinal disease with chronic or intermittent diarrhea, or disorders that increase the risk of diarrhea, such as inflammatory bowel disease.
* Have active leukemic involvement of the central nervous system (CNS).

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Cycle 1 (Up To 28 Days)
measure: Recommended Dose of LY3039478 in Combination With Dexamethasone
timeFrame: Cycle 1 (28 Days)
measure: Number of Participants Who Achieve Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi): Overall Remission Rate (ORR)
timeFrame: Baseline to Objective Disease Progression (Up To 2 Months)
Secondary outcomes:
measure: Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC[0-∞]) of LY3039478 in Combination With Dexamethasone in Day 1
timeFrame: Cycle 1 Day 1: Predose, 1-2, 3-4,6-8,24-30 hours
measure: Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC[0- 48]) of LY3039478 in Combination With Dexamethasone in Day 8
timeFrame: Cycle 1 Day 8: Predose, 1-2, 3-4,6-8,24-30 hours
measure: Number of Participants With CR or CRi and Notch-1 or FBXW7 Mutations
timeFrame: Baseline to Objective Disease Progression (Up To 12 Months)
measure: Phase 2: Number of Participants Who Achieve CR, CRi or Partial Remission (PR): Overall Remission Rate (ORR) Plus PR
timeFrame: Baseline to Objective Disease Progression (Up To 12 Months)
measure: Phase 2: Number of Participants Who Achieve PR
timeFrame: Baseline to Objective Disease Progression (Up To 12 Months)
measure: Phase 2: Duration of Remission (DoR)
timeFrame: Date of CR, CRi, or PR to Date of Relapse or Death from Any Cause (Approximately 1 Year)
measure: Phase 2:Relapse Free Survival (RFS)
timeFrame: Date of CR to Relapse or Death from any Cause (Approximately 1 Year)
measure: Phase 2: Event Free Survival (EFS)
timeFrame: Baseline to Objective Disease Progression or Death from Any Cause (Approximately 1 Year)
measure: Phase 2: Overall Survival (OS)
timeFrame: Baseline to the Date of Death from Any Cause (Approximately 1.5 Years)
measure: Phase 2: Change From Baseline in the Functional Assessment of Cancer Therapy-Leukemia-General (FACT-Leu-G) Score
timeFrame: Baseline, End of Study (Approximately 1.5 Years)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania Hospital
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas MD Anderson
state: Texas
city: LIlle
country: France
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.
city: Nantes
country: France
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.
city: Paris
country: France
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.
city: Pierre Benite
country: France
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.
city: Toulouse
country: France
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.
city: Frankfurt
country: Germany
facility: Johann Wolfgang Goethe-Universität Frankfurt
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Ulm
country: Germany
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.
city: Haifa
country: Israel
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Jerusalem
country: Israel
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Ramat Gan
country: Israel
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Tel Aviv
country: Israel
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Milano
country: Italy
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.
city: Napoli
country: Italy
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.
city: Torino
country: Italy
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Borthakur G, Martinelli G, Raffoux E, Chevallier P, Chromik J, Lithio A, Smith CL, Yuen E, Oakley GJ 3rd, Benhadji KA, DeAngelo DJ. Phase 1 study to evaluate Crenigacestat (LY3039478) in combination with dexamethasone in patients with T-cell acute lymphoblastic leukemia and lymphoma. Cancer. 2021 Feb 1;127(3):372-380. doi: 10.1002/cncr.33188. Epub 2020 Oct 27.