Acute LeukemiasPhase 2NCT01826214

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

A Phase 2 study testing LDE225 in people with Acute Leukemias, run by Novartis Pharmaceuticals at 23 sites in 11 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Acute Leukemias
What is being tested?: LDE225
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 70 participants
Where: 23 sitesin 11 countries
Study dates: May 2013to May 2015
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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)

Who cannot join

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

Trial locations and contacts

23 sites in 11 countries.

Country

City, postcode or hospital

23 sites in 11 countries

Germany4 sites

Novartis Investigative Site
Dresden, 01307
Novartis Investigative Site
Frankfurt, 60590
Novartis Investigative Site
Magdeburg, 39120
Novartis Investigative Site
Ulm, 89081

Other trials in Germany

Netherlands4 sites

Novartis Investigative Site
Amsterdam, 1081 HV
Novartis Investigative Site
Nijmegen, 6525 GA
Novartis Investigative Site
Rotterdam, 3015 CE
Novartis Investigative Site
Rotterdam, 3075 EA

Other trials in Netherlands

Australia2 sites

Novartis Investigative Site
Adelaide, South Australia, 5000
Novartis Investigative Site
Prahran, Victoria, 3181

Other trials in Australia

Austria2 sites

Novartis Investigative Site
Salzburg, 5020
Novartis Investigative Site
Vienna, 1090

Other trials in Austria

Belgium2 sites

Novartis Investigative Site
Leuven, 3000
Novartis Investigative Site
Yvoir, 5530

Other trials in Belgium

Canada2 sites

Novartis Investigative Site
Montreal, Quebec, H1T 2M4
Novartis Investigative Site
Montreal, Quebec, H3T 1E2

Other trials in Canada

Norway2 sites

Novartis Investigative Site
Bergen, NO-5021
Novartis Investigative Site
Trondheim, 7006

Other trials in Norway

Spain2 sites

Novartis Investigative Site
Salamanca, Castille and León, 37007
Novartis Investigative Site
Valencia, Valencia, 46026

Other trials in Spain

United States1 site

Duke University Medical Center SC-5
Durham, North Carolina, 27710

Other trials in United States

Hungary1 site

Novartis Investigative Site
Debrecen, 4032

Other trials in Hungary

United Kingdom1 site

Novartis Investigative Site
London, WC1E 6HX

Other trials in United Kingdom

About this study

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

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
Being tested: LDE225
Keywords: acute myeloid leukemia, AML, acute lymphoblastic leukemia, ALL, leukemia, acute, LDE225, adult patients, relapsed/refractory
Medical subject headings: Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LDE225Drug
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.

Study groups in NCT01826214
Study group	Role	What they receive
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. Receives: 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. Receives: Drug: LDE225

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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)
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.
Measured: 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
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.
Measured: Week 1 Day 1, Week 9 Day 1
Parmacokintics (PK) Parameter: Tmax
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.
Measured: Week 1 Day 1,Week 9 Day 1
Parmacokintics (PK) Parameter: AUC0-8h
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.
Measured: Week 1 Day 1,Week 9 Day 1
Parmacokintics (PK) Parameter: AUC0-24h
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.
Measured: Week 1 Day 1,Week 9 Day 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2013May 2015

First posted8 Apr 2013 (estimated)
Study startMay 2013
Primary completionMay 2015
Study completionMay 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Acute LeukemiasStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 70 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01826214
Sponsor's protocol ID: CLDE225X2203
Status last verified: Jul 2016
First submitted: 25 Mar 2013
Last updated: 30 Aug 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Acute Leukemias trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01826214
Acronym / sponsor ID: CLDE225X2203
Conditions: Acute Leukemias
Keywords: acute myeloid leukemia, AML, acute lymphoblastic leukemia, ALL, leukemia, acute, LDE225, adult patients
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 70 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: May 2013
Primary completion: May 2015 (actual)
Study completion: May 2015 (actual)
First posted: 8 Apr 2013 (estimated)
Results: Posted 20 May 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
LDE225-400	Experimental	Drug: LDE225Patients 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.
LDE225-800	Experimental	Drug: LDE225Patients 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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)

Key exclusion criteria (4 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LDE225LDE225 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.	Drug	LDE225-400, LDE225-800

Primary outcome

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.
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.

5 secondary outcomes

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
Parmacokintics (PK) Parameter: Cmax
Time frame: Week 1 Day 1, Week 9 Day 1
Parmacokintics (PK) Parameter: Tmax
Time frame: Week 1 Day 1,Week 9 Day 1
Parmacokintics (PK) Parameter: AUC0-8h
Time frame: Week 1 Day 1,Week 9 Day 1
Parmacokintics (PK) Parameter: AUC0-24h
Time frame: Week 1 Day 1,Week 9 Day 1

Results and safety

Results posted to the registry on 20 May 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
LDE225-400	35	0
LDE225-800	34	0

Primary outcome: 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. Number. Unit: Participants

Measure	LDE225-400 n = 35	LDE225-800 n = 35
Value	0	0

Population analysed: Full analysis set (FAS): comprised of all patients who were randomized to a study treatment. According to the intent-to-treat principle, patient data were analyzed according to the treatment to which they had been randomized. No statistical analysis were reported in this study.

Primary outcome: 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. Number. Unit: Participants

Measure	LDE225-400 n = 35	LDE225-800 n = 35
Value	1	0

5 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
LDE225-400	25 of 35 (71.4%)	35 of 35 (100%)	Not reported
LDE225-800	25 of 34 (73.5%)	34 of 34 (100%)	Not reported

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

23 sites in 11 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing LDE225 in people with Acute Leukemias, run by Novartis Pharmaceuticals at 23 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in Germany, Netherlands, Australia, Austria, Belgium and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01826214.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2016.