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

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.
ClinicalTrials.gov Identifier: NCT02518113
Recruitment Status : Completed
First Posted : August 7, 2015
Results First Posted : February 6, 2019
Last Update Posted : February 6, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

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).

Condition or disease Intervention/treatment Phase
T-cell Acute Lymphoblastic Leukemia T-cell Lymphoblastic Lymphoma Drug: LY3039478 Drug: Dexamethasone Drug: Placebo Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/Randomized Phase 2 Study to Evaluate LY3039478 in Combination With Dexamethasone in T-ALL/T-LBL Patients
Actual Study Start Date : October 1, 2015
Actual Primary Completion Date : January 15, 2018
Actual Study Completion Date : January 15, 2018


Arm Intervention/treatment
Experimental: LY3039478 + Dexamethasone (Adult)

Part A: 50 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression.

75 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression.

100 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression.

125 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression.

Drug: LY3039478
Administered orally

Drug: Dexamethasone
Administered orally

Experimental: LY3039478 + Dexamethasone (Pediatric)

Part B: LY3039478 administered orally TIW at escalating doses and dexamethasone administered orally twice a day (BID) on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression.

There were no participants enrolled to Part B of the study.

Drug: LY3039478
Administered orally

Drug: Dexamethasone
Administered orally

Experimental: Phase 2: LY3039478 + Dexamethasone

LY3039478 administered orally TIW and dexamethasone administered orally BID on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression.

There were no participants enrolled to Phase 2 of the study.

Drug: LY3039478
Administered orally

Drug: Dexamethasone
Administered orally

Placebo Comparator: Phase 2: Placebo + Dexamethasone

Placebo administered orally TIW and dexamethasone administered orally BID on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression.

There were no participants enrolled to Phase 2 of the study.

Drug: Dexamethasone
Administered orally

Drug: Placebo
Administered orally




Primary Outcome Measures :
  1. Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: Cycle 1 (Up To 28 Days) ]
    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).

  2. Recommended Dose of LY3039478 in Combination With Dexamethasone [ Time Frame: Cycle 1 (28 Days) ]
    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.

  3. Number of Participants Who Achieve Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi): Overall Remission Rate (ORR) [ Time Frame: Baseline to Objective Disease Progression (Up To 2 Months) ]
    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.


Secondary Outcome Measures :
  1. Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC[0-∞]) of LY3039478 in Combination With Dexamethasone in Day 1 [ Time Frame: Cycle 1 Day 1: Predose, 1-2, 3-4,6-8,24-30 hours ]
    Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC[0-∞]) of LY3039478 in Combination with Dexamethasone in Day 1

  2. Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC[0- 48]) of LY3039478 in Combination With Dexamethasone in Day 8 [ Time Frame: Cycle 1 Day 8: Predose, 1-2, 3-4,6-8,24-30 hours ]
    Pharmacokinetics (PK): Area Under the Concentration-Time Curve (AUC[0- 48]) of LY3039478 in Combination with Dexamethasone in Day 8

  3. Number of Participants With CR or CRi and Notch-1 or FBXW7 Mutations [ Time Frame: Baseline to Objective Disease Progression (Up To 12 Months) ]
    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.

  4. Phase 2: Number of Participants Who Achieve CR, CRi or Partial Remission (PR): Overall Remission Rate (ORR) Plus PR [ Time Frame: Baseline to Objective Disease Progression (Up To 12 Months) ]
  5. Phase 2: Number of Participants Who Achieve PR [ Time Frame: Baseline to Objective Disease Progression (Up To 12 Months) ]
  6. Phase 2: Duration of Remission (DoR) [ Time Frame: Date of CR, CRi, or PR to Date of Relapse or Death from Any Cause (Approximately 1 Year) ]
  7. Phase 2:Relapse Free Survival (RFS) [ Time Frame: Date of CR to Relapse or Death from any Cause (Approximately 1 Year) ]
  8. Phase 2: Event Free Survival (EFS) [ Time Frame: Baseline to Objective Disease Progression or Death from Any Cause (Approximately 1 Year) ]
  9. Phase 2: Overall Survival (OS) [ Time Frame: Baseline to the Date of Death from Any Cause (Approximately 1.5 Years) ]
  10. Phase 2: Change From Baseline in the Functional Assessment of Cancer Therapy-Leukemia-General (FACT-Leu-G) Score [ Time Frame: Baseline, End of Study (Approximately 1.5 Years) ]


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.


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Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

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 ClinicalTrials.gov identifier (NCT number): NCT02518113


Locations
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United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010-0269
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Michigan
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Pennsylvania
University of Pennsylvania Hospital
Philadelphia, Pennsylvania, United States, 19106
United States, Texas
University of Texas MD Anderson
Houston, Texas, United States, 77030
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, 59037
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, 44093
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, 75475
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, 69495
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, France, 31059
Germany
Johann Wolfgang Goethe-Universität Frankfurt
Frankfurt, Germany, 60590
Universitätsklinikum Heidelberg
Heidelberg, Germany, 69120
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, Germany, 89081
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, 3525408
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, 9112001
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, 5266202
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, Israel, 6423906
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, 20132
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, 80131
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, Italy, 10126
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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Study Director: 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) Eli Lilly and Company
  Study Documents (Full-Text)

Documents provided by Eli Lilly and Company:
Study Protocol  [PDF] June 4, 2015
Statistical Analysis Plan  [PDF] June 17, 2015


Additional Information:
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02518113     History of Changes
Other Study ID Numbers: 14548
I6F-MC-JJCB ( Other Identifier: Eli Lilly and Company )
2014-005024-10 ( EudraCT Number )
First Posted: August 7, 2015    Key Record Dates
Results First Posted: February 6, 2019
Last Update Posted: February 6, 2019
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
URL: https://www.clinicalstudydatarequest.com/

Additional relevant MeSH terms:
Layout table for MeSH terms
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Dexamethasone acetate
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action