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

Lilly

Status and phase: Completed; Phase 2; Phase 1

Conditions: T-cell Lymphoblastic Lymphoma; T-cell Acute Lymphoblastic Leukemia

Treatments: Drug: Placebo; Drug: Dexamethasone; Drug: LY3039478

Study type: Interventional

Funder types: Industry

Identifiers

NCT02518113

14548

I6F-MC-JJCB (Other Identifier)

2014-005024-10 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 36 patients

Sex: All

Ages: 2+ years old

Volunteers: No Healthy Volunteers

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• Have previously completed or withdrawn from this study or any other study investigating LY3039478 or other Notch inhibitors.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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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36 participants in 4 patient groups, including a placebo group

LY3039478 + Dexamethasone (Adult)

Experimental group

Description:

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.

Treatment:

Drug: LY3039478

Drug: Dexamethasone

LY3039478 + Dexamethasone (Pediatric)

Experimental group

Description:

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.

Treatment:

Drug: LY3039478

Drug: Dexamethasone

Phase 2: LY3039478 + Dexamethasone

Experimental group

Description:

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.

Treatment:

Drug: LY3039478

Drug: Dexamethasone

Phase 2: Placebo + Dexamethasone

Placebo Comparator group

Description:

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.

Treatment:

Drug: Dexamethasone

Drug: Placebo