A Study of LY3039478 in Combination With Dexamethasone in Participants With T-ALL/T-LBL

T-cell Acute Lymphoblastic Leukemia Clinical Trial

Official title:

A Phase 1b/Randomized Phase 2 Study to Evaluate LY3039478 in Combination With Dexamethasone in T-ALL/T-LBL Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02518113
• Other study ID #: 14548
• Secondary ID: I6F-MC-JJCB2014-
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: October 1, 2015
• Est. completion date: January 15, 2018

Study information

• Verified date: August 2019
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: January 15, 2018
• Est. primary completion date: January 15, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years and older

Eligibility

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• Have previously completed or withdrawn from this study or any other study investigating LY3039478 or other Notch inhibitors.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).

Related Conditions & MeSH terms

• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
• T-cell Acute Lymphoblastic Leukemia
• T-cell Lymphoblastic Lymphoma

Intervention

Drug:
• LY3039478
Administered orally
• Dexamethasone
Administered orally
• Placebo
Administered orally

Locations

Country	Name	City	State
France	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.	LIlle
France	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.	Nantes
France	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.	Paris
France	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.	Pierre Benite
France	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.	Toulouse
Germany	Johann Wolfgang Goethe-Universität Frankfurt	Frankfurt
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	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.	Ulm
Israel	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.	Haifa
Israel	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.	Jerusalem
Israel	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.	Ramat Gan
Israel	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.	Tel Aviv
Italy	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.	Milano
Italy	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.	Napoli
Italy	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.	Torino
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope National Medical Center	Duarte	California
United States	University of Texas MD Anderson	Houston	Texas
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Pennsylvania Hospital	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  France,  Germany,  Israel,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Dose Limiting Toxicities (DLTs)	A DLT was an Adverse Event(AE) observed during the first 28 day cycle that is determined by the investigator to be at least possibly related to LY3039478 according to CTCAE v 4.0 and fulfills any of the following criteria: CTCAE Grade 3 nonhematological toxicity with a few exceptions, any other significant toxicity deemed to be dose limiting (eg, any toxicity that is possibly related to the study medication that requires the withdrawal of the patient from the study during Cycle 1).	Cycle 1 (Up To 28 Days)
Primary	Recommended Dose of LY3039478 in Combination With Dexamethasone	A DLT was an Adverse Event(AE) observed during the first 28 day cycle that is determined by the investigator to be at least possibly related to LY3039478 according to CTCAE v 4.0 and fulfills any of the following criteria:CTCAE Grade 3 nonhematological toxicity with a few exceptions, any other significant toxicity deemed to be dose limiting.A dose-limiting equivalent toxicity (DLET) was defined as an AE occurring between Day 1 and Day 28 of any cycle (other than Cycle 1) for a patient enrolled in the Phase 1 portion or in any cycle (including Cycle 1) for a patient enrolled in the Phase 2 portion that would have met the criteria for DLT if it had occurred during Cycle 1 for a patient enrolled in the Phase 1 portion.	Cycle 1 (28 Days)
Primary	Number of Participants Who Achieve Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi): Overall Remission Rate (ORR)	ORR is defined as the number of participants who achieved a best overall response of either complete remission (CR) or incomplete remission (CRi). The ORR (CR and CRi) is the sum of patients achieving a CR or a CRi divided by the total number of patients randomized in that arm. CR is defined as the number of participants who achieved a best overall response of complete remission (CR), out of the total number of participants randomized in that arm.	Baseline to Objective Disease Progression (Up To 2 Months)
Secondary	Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC[0-8]) of LY3039478 in Combination With Dexamethasone in Day 1	Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC[0-8]) of LY3039478 in Combination with Dexamethasone in Day 1	Cycle 1 Day 1: Predose, 1-2, 3-4,6-8,24-30 hours
Secondary	Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC[0- 48]) of LY3039478 in Combination With Dexamethasone in Day 8	Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC[0- 48]) of LY3039478 in Combination with Dexamethasone in Day 8	Cycle 1 Day 8: Predose, 1-2, 3-4,6-8,24-30 hours
Secondary	Number of Participants With CR or CRi and Notch-1 or FBXW7 Mutations	ORR is defined as the number of participants who achieved a best overall response of either complete remission (CR) or incomplete remission (CRi). The ORR (CR and CRi) is the sum of participants achieving a CR or a CRi divided by the total number of participants randomized in that arm. CR is defined as the number of participants who achieved a best overall response of complete remission (CR), out of the total number of participants randomized in that arm.	Baseline to Objective Disease Progression (Up To 12 Months)
Secondary	Phase 2: Number of Participants Who Achieve CR, CRi or Partial Remission (PR): Overall Remission Rate (ORR) Plus PR		Baseline to Objective Disease Progression (Up To 12 Months)
Secondary	Phase 2: Number of Participants Who Achieve PR		Baseline to Objective Disease Progression (Up To 12 Months)
Secondary	Phase 2: Duration of Remission (DoR)		Date of CR, CRi, or PR to Date of Relapse or Death from Any Cause (Approximately 1 Year)
Secondary	Phase 2:Relapse Free Survival (RFS)		Date of CR to Relapse or Death from any Cause (Approximately 1 Year)
Secondary	Phase 2: Event Free Survival (EFS)		Baseline to Objective Disease Progression or Death from Any Cause (Approximately 1 Year)
Secondary	Phase 2: Overall Survival (OS)		Baseline to the Date of Death from Any Cause (Approximately 1.5 Years)
Secondary	Phase 2: Change From Baseline in the Functional Assessment of Cancer Therapy-Leukemia-General (FACT-Leu-G) Score		Baseline, End of Study (Approximately 1.5 Years)

External Links

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