Study of Efficacy and Safety of LDE225 in Adult Patients With Relapsed/Refractory Acute Leukemia

NCT01826214 | Completed Phase 2 Results DMC

• 1 other identifier: CLDE225X2203
• Study Type: interventional
• Target: 70
• Locations: 10 countries
• Sites: 21

Brief Summary

The study will evaluate the efficacy, safety and tolerability of two dosing schedules of LDE225 in patients with relapsed/refractory acute leukemia or elderly patients with untreated acute leukemia.

Conditions

Acute Leukemias

Keywords

acute myeloid leukemia; AML; acute lymphoblastic leukemia; ALL; leukemia; acute; LDE225; adult patients; relapsed/refractory

Outcome Measures

Primary Outcomes (2)

• Rate of Complete Remission (CR)

  Complete Response (CR) was based on the International Working Group (IWG) criteria based on weekly peripheral blood count measurements and bone marrow biopsy/aspiration collection. Efficacy assessments were performed to determine CR. A treatment cycle was defined as 4 weeks. The outcome measure for the study is based on standardized response criteria as defined by the International Working Group (IWG) for AML. The IWG was established by a group of investigators interested in the design and conduct of clinical trials in acute myeloid leukemia (AML). The criteria established by this group (a set of recommendations for response assessment) are well established, endorsed by major institutions and Health Authorities, and are widely used in clinical trials. No statistical analysis was planned for this primary outcome.

  at screening, every week up to Week 9, every 2 weeks thereafter until CR, every 4 weeks after CR up to 24 months

• Complete Remission With Incomplete Blood Count Recovery (CRi)

  The other primary efficacy endpoint was CRi based on the International Working Group (IWG) criteria based on weekly peripheral blood count measurements and bone marrow biopsy/aspiration collection. Efficacy assessments were performed to determine CRi. A treatment cycle was defined as 4 weeks. No statistical analysis was planned for this primary outcome.

  within 3 days after clearance of blasts from peripheral blood (PB), monthly thereafter until CR or reappearance of blasts in the PB, after CR every other month until discontination up to 24 months

Secondary Outcomes (5)

• Overall Response Rate (ORR)

  Every 8 weeks for the first 6 months and every 12 weeks until 53 weeks after the last patient is enrolled or until relapse up to 24 months

• Parmacokintics (PK) Parameter: Cmax

  Week 1 Day 1, Week 9 Day 1

• Parmacokintics (PK) Parameter: Tmax

  Week 1 Day 1,Week 9 Day 1

• Parmacokintics (PK) Parameter: AUC0-8h

  Week 1 Day 1,Week 9 Day 1

• Parmacokintics (PK) Parameter: AUC0-24h

  Week 1 Day 1,Week 9 Day 1

Study Arms (2)

LDE225-400

EXPERIMENTAL

Patients who were randomized to Schedule A, and received 400 mg LDE225 twice daily for the first two weeks only and then after two weeks, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.

Drug: LDE225

LDE225-800

EXPERIMENTAL

Patients who were randomized to Schedule B, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.

Drug: LDE225

Interventions

LDE225 DRUG

LDE225 will be supplied as 200 mg capsules by Novartis. Patients will receive study treatment on an outpatient basis. LDE225 will be dispensed every two weeks for the first four weeks and at the start of every four weeks thereafter, as needed.

LDE225-400; LDE225-800

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have relapsed or primary refractory non-M3 acute myeloid leukemia or relapsed or refractory non-T-cell acute lymphoblastic leukemia or untreated acute myeloid leukemia in elderly patients.
• Performance status of 0, 1 or 2 per WHO classification.
• Adequate renal and liver function.
• Adequate blood creatine kinase value (CK \< 1.5ULN)

You may not qualify if:

• Allogeneic stem cell transplantation within the last 4 months and/or active graft versus host disease requiring systemic immunosuppressant therapy, or autologous stem cell transplantation within the last 4 weeks.
• Patient for which immediate allogeneic stem cell transplantation is the treatment of choice.
• Pregnant or nursing (lactating) women.
• Active CNS leukemic involvement

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (23)

Duke University Medical Center SC-5

Durham, North Carolina, 27710, United States

Location

Novartis Investigative Site

Adelaide, South Australia, 5000, Australia

Location

Novartis Investigative Site

Prahran, Victoria, 3181, Australia

Location

Novartis Investigative Site

Salzburg, 5020, Austria

Location

Novartis Investigative Site

Vienna, 1090, Austria

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Yvoir, 5530, Belgium

Location

Novartis Investigative Site

Montreal, Quebec, H1T 2M4, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H3T 1E2, Canada

Location

Novartis Investigative Site

Dresden, 01307, Germany

Location

Novartis Investigative Site

Frankfurt, 60590, Germany

Location

Novartis Investigative Site

Magdeburg, 39120, Germany

Location

Novartis Investigative Site

Ulm, 89081, Germany

Location

Novartis Investigative Site

Debrecen, 4032, Hungary

Location

Novartis Investigative Site

Amsterdam, 1081 HV, Netherlands

Location

Novartis Investigative Site

Nijmegen, 6525 GA, Netherlands

Location

Novartis Investigative Site

Rotterdam, 3015 CE, Netherlands

Location

Novartis Investigative Site

Rotterdam, 3075 EA, Netherlands

Location

Novartis Investigative Site

Bergen, NO-5021, Norway

Location

Novartis Investigative Site

Trondheim, 7006, Norway

Location

Novartis Investigative Site

Salamanca, Castille and León, 37007, Spain

Location

Novartis Investigative Site

Valencia, Valencia, 46026, Spain

Location

Novartis Investigative Site

London, WC1E 6HX, United Kingdom

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia; Recurrence

Interventions

sonidegib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Only 34 of the 35 patients in the LDE225 800 mg once daily arm received at least dose of study drug were analyzed for safety.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

trialandresults.registries@novartis.com

82-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2013
• First Posted: April 8, 2013
• Study Start: May 1, 2013
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: August 30, 2016
• Results First Posted: May 20, 2016

Record last verified: 2016-07

Locations

AU (2); US (1); HU (1); NO (2); BE (2); NL (4); ES (2); CA (2); DE (4); GB (1)