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

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ClinicalTrials.gov Identifier: NCT01826214
Recruitment Status : Completed
First Posted : April 8, 2013
Results First Posted : May 20, 2016
Last Update Posted : August 30, 2016
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
Acute Leukemias Drug: LDE225 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Multi-center, Open Label, Randomized Study to Assess Safety and Efficacy of Two Different Schedules of Oral LDE225 in Adult Patients With Relapsed/Refractory or Untreated Elderly Patients With Acute Leukemia
Study Start Date : May 2013
Actual Primary Completion Date : May 2015
Actual Study Completion Date : May 2015


Arm Intervention/treatment
Experimental: LDE225-400
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 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.

Experimental: LDE225-800
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
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.




Primary Outcome Measures :
  1. Rate of Complete Remission (CR) [ Time Frame: at screening, every week up to Week 9, every 2 weeks thereafter until CR, every 4 weeks after CR up to 24 months ]
    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.

  2. Complete Remission With Incomplete Blood Count Recovery (CRi) [ Time Frame: 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 ]
    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.


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: 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 ]
    ORR was the rate of complete remission (CR), complete remission with incomplete blood count recovery (CRi) or partial response (PR) according to IWG criteria. CR, CRi or PR will be assessed through bone marrow biopsy/aspirate and peripheral blood blasts counts.

  2. Parmacokintics (PK) Parameter: Cmax [ Time Frame: Week 1 Day 1, Week 9 Day 1 ]
    Cmax is the maximum observed plasma concentration after drug administration.The PK parameters were determined in plasma using non-compartmental methods. A PK sample was excluded from analyses if the patient vomited within the first 4 hours following the last oral dose of study drug. Other PK samples were excluded as deemed appropriate by the pharmacokineticist. Cmax was derived from the PK concentrations collected at 0, 0.5, 1, 2, 4, 6, 8 and 24 hours post dose on W1D1 and W9D1. The PK concentration at each time point is not an endpoint in the protocol, but these concentrations are used to derive the PK parameters.

  3. Parmacokintics (PK) Parameter: Tmax [ Time Frame: Week 1 Day 1,Week 9 Day 1 ]
    Tmax is the time to reach Cmax. The PK parameters were determined in plasma using non-compartmental methods. A PK sample was excluded from analyses if the patient vomited within the first 4 hours following the last oral dose of study drug. Other PK samples were excluded as deemed appropriate by the Pharmacokineticist. Tmax was derived from the PK concentrations collected at 0, 0.5, 1, 2, 4, 6, 8 and 24 hours post dose on W1D1 and W9D1. The PK concentration at each time point is not an endpoint in the protocol, but these concentrations are used to derive the PK parameters.

  4. Parmacokintics (PK) Parameter: AUC0-8h [ Time Frame: Week 1 Day 1,Week 9 Day 1 ]
    AUC0-8h is the area under the concentration-time curve from time zero to 8 hours. The PK parameters were determined in plasma using non-compartmental methods. A PK sample was excluded from analyses if the patient vomited within the first 4 hours following the last oral dose of study drug. Other PK samples were excluded as deemed appropriate by the Pharmacokineticist. AUC0-8h was derived from the PK concentrations collected at 0, 0.5, 1, 2, 4, 6, 8 and 24 hours post dose on W1D1 and W9D1. The PK concentration at each time point is not an endpoint in the protocol, but these concentrations are used to derive the PK parameters.

  5. Parmacokintics (PK) Parameter: AUC0-24h [ Time Frame: Week 1 Day 1,Week 9 Day 1 ]
    AUC0-24 is the area under the concentration-time curve from time zero to 24 hours done only on 800 mg once a day schedule. The PK parameters were determined in plasma using non-compartmental methods. A PK sample was excluded from analyses if the patient vomited within the first 4 hours following the last oral dose of study drug. Other PK samples were excluded as deemed appropriate by the Pharmacokineticist. AUC0-24h was derived from the PK concentrations collected at 0, 0.5, 1, 2, 4, 6, 8 and 24 hours post dose on W1D1 and W9D1. The PK concentration at each time point is not an endpoint in the protocol, but these concentrations are used to derive the PK parameters.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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

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): NCT01826214


Locations
United States, North Carolina
Duke University Medical Center SC-5
Durham, North Carolina, United States, 27710
Australia, South Australia
Novartis Investigative Site
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Novartis Investigative Site
Prahran, Victoria, Australia, 3181
Austria
Novartis Investigative Site
Salzburg, Austria, 5020
Novartis Investigative Site
Wien, Austria, 1090
Belgium
Novartis Investigative Site
Leuven, Belgium, 3000
Novartis Investigative Site
Yvoir, Belgium, 5530
Canada, Quebec
Novartis Investigative Site
Montreal, Quebec, Canada, H1T 2M4
Novartis Investigative Site
Montreal, Quebec, Canada, H3T 1E2
Germany
Novartis Investigative Site
Dresden, Germany, 01307
Novartis Investigative Site
Frankfurt, Germany, 60590
Novartis Investigative Site
Magdeburg, Germany, 39120
Novartis Investigative Site
Ulm, Germany, 89081
Hungary
Novartis Investigative Site
Debrecen, Hungary, 4032
Netherlands
Novartis Investigative Site
Amsterdam, Netherlands, 1081 HV
Novartis Investigative Site
Nijmegen, Netherlands, 6525 GA
Novartis Investigative Site
Rotterdam, Netherlands, 3015 CE
Novartis Investigative Site
Rotterdam, Netherlands, 3075 EA
Norway
Novartis Investigative Site
Bergen, Norway, NO-5021
Novartis Investigative Site
Trondheim, Norway, 7006
Spain
Novartis Investigative Site
Salamanca, Castilla y Leon, Spain, 37007
Novartis Investigative Site
Valencia, Comunidad Valenciana, Spain, 46026
United Kingdom
Novartis Investigative Site
London, United Kingdom, WC1E 6HX
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01826214     History of Changes
Other Study ID Numbers: CLDE225X2203
First Posted: April 8, 2013    Key Record Dates
Results First Posted: May 20, 2016
Last Update Posted: August 30, 2016
Last Verified: July 2016

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
acute myeloid leukemia
AML
acute lymphoblastic leukemia
ALL
leukemia
acute
LDE225
adult patients
relapsed/refractory

Additional relevant MeSH terms:
Leukemia
Acute Disease
Neoplasms by Histologic Type
Neoplasms
Disease Attributes
Pathologic Processes