Myelodysplastic Syndromes (MDS)Phase 1NCT01613976

A Phase Ib Study of Panobinostat (LBH589) in Combination With 5-Azacitidine for Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML) or Acute Myeloid Leukemia (AML) Patients

A Phase 1 study testing Panobinostat in people with Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML), run by Novartis Pharmaceuticals at 6 sites in Japan.

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 purpose of this study is to confirm the safety and tolerability of oral panobinostat (PAN) in combination with a fixed dose of 5-Azacitidine (5-Aza) in adult Japanese patients with Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML) or Acute Myeloid Leukemia (AML). Read more about this study

Who is it for?: Ages 20 years and older
Conditions the study is for: Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), Acute Myeloid Leukemia (AML)
What is being tested?: Panobinostat
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 10 participants
Where: 6 sitesJapan
Study dates: Aug 2012to May 2014
Phase: Phase 1
Are there results?: None posted in the registry

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

Who may be able to join

Japanese patients who are candidates for treatment with 5-Aza and present with one of the following:
intermediate-2 or high-risk MDS according to the International Prognostic Scoring System (IPSS). OR
AML with multilineage dysplasia and maximum of 30% blasts (former RAEB-T according to FAB) OR CMML
Patient has an ECOG performance status of ≤ 2
Patients must have the following laboratory values unless elevations are considered due to MDS or leukemia: AST/SGOT and/or ALT/SGPT ≤ 2.5 x ULN; serum creatinine ≤ 1.5 x ULN; serum bilirubin (total and direct) ≤ 2 x ULN; electrolyte panel without clinically relevant abnormalities

Who cannot join

Patient who is planned for or has history of hematopoietic stem-cell transplantation (HSCT)
Patients with relapsed/refractory AML
Patient is receiving concurrent anti-cancer therapy
Patient has received prior treatment with deacetylase inhibitors (DACi)
Patient has received prior treatment with 5-Aza or 6-aza-2'-deoxycytidine (decitabine)
7. Patient has shown suspected hypersensitivity to 5-Aza or Mannitol 8. Patients with impaired cardiac function 9. Patient taking medications with relative risk of prolonging the QT interval or inducing Torsade de pontes if such treatment cannot be discontinued or switched to a different medication prior to starting study treatment 10. Patients with clinical evidence of relevant mucosal or internal bleeding 11. Patient has any other concurrent severe and/or uncontrolled medical conditions
Other protocol-defined inclusion/exclusion criteria may apply

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

Japan6 sites

Novartis Investigative Site
Chuo-ku, Tokyo, 104-0045
Novartis Investigative Site
Kobe, Hyōgo, 650-0017
Novartis Investigative Site
Kyoto, 602-8566
Novartis Investigative Site
Nagoya, Aichi-ken, 460-0001
Novartis Investigative Site
Nagoya, Aichi-ken, 466-8650
Novartis Investigative Site
Sendai, Miyagi, 980-8574

Other trials in Japan

About this study

Official title: A Phase Ib, Open-label, Multi-center, Dose-escalation Study of Oral Panobinostat (LBH589) Administered With 5-Azacitidine (Vidaza®) in Adult Japanese Patients With Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML) or Acute Myeloid Leukemia (AML)

Conditions: Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), Acute Myeloid Leukemia (AML)
Being tested: Panobinostat
Keywords: Myelodysplastic Syndromes, MDS, Chronic Myelomonocytic Leukemia, CMML, Acute Myeloid Leukemia, AML, Panobinostat, LBH589, 5-Aza, Azacitidine
Medical subject headings: Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic, Leukemia, Myeloid, Acute

What participants receive

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

PanobinostatDrug
Also called LBH589

Study groups in NCT01613976
Study group	Role	What they receive
Panobinostat and Azacitidine	Experimental	combination regimen Receives: Drug: Panobinostat

What is being measured

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

Incidence of Dose Limiting Toxicitiy(DLT)
DLT will be assessed during PK run-in period (up to 7 days) and 1st cycle (28 days)
Measured: first 5 weeks of treatment period

Secondary outcomes (8)

PK parameter - Cmax
Measured: Day 1 to 3 of PK run-in period; pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 24 and 48 hours
PK parameter - Tmax
Measured: Day 1 to 3 of PK run-in period; pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 24 and 48 hours
PK parameter - AUC (AUC0-48, AUC0-tlast)
Measured: Day 1 to 3 of PK run-in period; pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 24 and 48 hours
PK parameter - T1/2 (apparent oral clearance, volume distribution)
Measured: Day 1 to 3 of PK run-in period; pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 24 and 48 hours
PK parameter - AUC0-inf
Measured: Day 1 to 3 of PK run-in period; pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 24 and 48 hours
Trough level of PAN in combination with 5-Aza
Measured: Day 4, 5, 8 of the 1st cycle; pre-dose (0 hour)
Frequency and severity of Adverse Events (AEs)
Safety will be measured in terms of type, frequency and severity of adverse events according to CTCAE v4.03.
Measured: Participants will be followed for the duration of treatment, an expected average of 6 months
Laboratory abnormalities
Measured: duration of treatment, an expected average of 6 months

Timeline

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

Aug 2012May 2014

First posted7 Jun 2012 (estimated)
Study startAug 2012
Primary completionMay 2014
Study completionMay 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Myelodysplastic Syndromes (MDS)Studies 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 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 10 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01613976
Sponsor's protocol ID: CLBH589H1101
Status last verified: Dec 2020
First submitted: 24 May 2012
Last updated: 19 Dec 2020
Results posted: No
Data monitoring committee: No

Publications

Kobayashi Y, Munakata W, Ogura M, Uchida T, Taniwaki M, Kobayashi T, Shimada F, Yonemura M, Matsuoka F, Tajima T, Yakushijin K, Minami H. Phase I study of panobinostat and 5-azacitidine in Japanese patients with myelodysplastic syndrome or chronic myelomonocytic leukemia. Int J Hematol. 2018 Jan;107(1):83-91. doi: 10.1007/s12185-017-2327-9. Epub 2017 Sep 13.
PubMed 28905323

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

RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 1/2
Omacetaxine + Azacitidine in Untreated Patients With High Grade MDS
High Grade Myelodysplastic Syndromes
RecruitingPhase 1/2
Pacritinib, a Kinase Inhibitor of CSF1R, IRAK1, JAK2, and FLT3, in Adults and Pediatric Participants 12 Years of Age or Older With Myelodysplastic Syndromes or Myelodysplastic/Myeloproliferative Neoplasms
Myelodysplastic Syndromes
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome

All Myelodysplastic Syndromes (MDS) trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase Ib, Open-label, Multi-center, Dose-escalation Study of Oral Panobinostat (LBH589) Administered With 5-Azacitidine (Vidaza®) in Adult Japanese Patients With Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML) or Acute Myeloid Leukemia (AML)
ClinicalTrials.gov ID: NCT01613976
Acronym / sponsor ID: CLBH589H1101
Conditions: Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), Acute Myeloid Leukemia (AML)
Keywords: Myelodysplastic Syndromes, MDS, Chronic Myelomonocytic Leukemia, CMML, Acute Myeloid Leukemia, AML, Panobinostat, LBH589
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 10 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Aug 2012
Primary completion: May 2014 (actual)
Study completion: May 2014 (actual)
First posted: 7 Jun 2012 (estimated)
Results: Not posted in the source record

Clinical summary

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

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Panobinostat and Azacitidine	Experimental	Drug: Panobinostatcombination regimen

Who may qualify

Ages: 20 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Japanese patients who are candidates for treatment with 5-Aza and present with one of the following:
Patient has an ECOG performance status of ≤ 2
Patients must have the following laboratory values unless elevations are considered due to MDS or leukemia: AST/SGOT and/or ALT/SGPT ≤ 2.5 x ULN; serum creatinine ≤ 1.5 x ULN; serum bilirubin (total and direct) ≤ 2 x ULN; electrolyte panel without clinically relevant abnormalities

Key exclusion criteria (7 listed)

Patient who is planned for or has history of hematopoietic stem-cell transplantation (HSCT)
Patients with relapsed/refractory AML
Patient is receiving concurrent anti-cancer therapy
Patient has received prior treatment with deacetylase inhibitors (DACi)
Patient has received prior treatment with 5-Aza or 6-aza-2'-deoxycytidine (decitabine)

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
PanobinostatAlso: LBH589	Drug	Panobinostat and Azacitidine

Primary outcome

Incidence of Dose Limiting Toxicitiy(DLT)
Time frame: first 5 weeks of treatment period
DLT will be assessed during PK run-in period (up to 7 days) and 1st cycle (28 days)

8 secondary outcomes

PK parameter - Cmax
Time frame: Day 1 to 3 of PK run-in period; pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 24 and 48 hours
PK parameter - Tmax
Time frame: Day 1 to 3 of PK run-in period; pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 24 and 48 hours
PK parameter - AUC (AUC0-48, AUC0-tlast)
Time frame: Day 1 to 3 of PK run-in period; pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 24 and 48 hours
PK parameter - T1/2 (apparent oral clearance, volume distribution)
Time frame: Day 1 to 3 of PK run-in period; pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 24 and 48 hours
PK parameter - AUC0-inf
Time frame: Day 1 to 3 of PK run-in period; pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 24 and 48 hours
Trough level of PAN in combination with 5-Aza
Time frame: Day 4, 5, 8 of the 1st cycle; pre-dose (0 hour)
Frequency and severity of Adverse Events (AEs)
Time frame: Participants will be followed for the duration of treatment, an expected average of 6 months
Laboratory abnormalities
Time frame: duration of treatment, an expected average of 6 months

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2020.
Derived from this study: PubMed 28905323Kobayashi Y, Munakata W, Ogura M, Uchida T, Taniwaki M, Kobayashi T, Shimada F, Yonemura M, Matsuoka F, Tajima T, Yakushijin K, Minami H. Phase I study of panobinostat and 5-azacitidine in Japanese patients with myelodysplastic syndrome or chronic myelomonocytic leukemia. Int J Hematol. 2018 Jan;107(1):83-91. doi: 10.1007/s12185-017-2327-9. Epub 2017 Sep 13.
Novartis results databaseLink provided by the sponsor.

Related trials for Myelodysplastic Syndromes (MDS)

RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 1/2
Omacetaxine + Azacitidine in Untreated Patients With High Grade MDS
High Grade Myelodysplastic Syndromes
RecruitingPhase 1/2
Pacritinib, a Kinase Inhibitor of CSF1R, IRAK1, JAK2, and FLT3, in Adults and Pediatric Participants 12 Years of Age or Older With Myelodysplastic Syndromes or Myelodysplastic/Myeloproliferative Neoplasms
Myelodysplastic Syndromes
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome

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

6 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Panobinostat in people with Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML), run by Novartis Pharmaceuticals at 6 sites in Japan.

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 5 inclusion and 7 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 19 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Japan. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Incidence of Dose Limiting Toxicitiy(DLT) (time frame: first 5 weeks of treatment period). 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 NCT01613976, which also lists 1 linked publication.

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 19 Dec 2020.