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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01613976
First received: May 24, 2012
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

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).


Condition Intervention Phase
Myelodysplastic Syndromes (MDS)
Chronic Myelomonocytic Leukemia (CMML)
Acute Myeloid Leukemia (AML)
Drug: Panobinostat
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Incidence of Dose Limiting Toxicitiy(DLT) [ Time Frame: first 5 weeks of treatment period ] [ Designated as safety issue: Yes ]
    DLT will be assessed during PK run-in period (up to 7 days) and 1st cycle (28 days)


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Trough level of PAN in combination with 5-Aza [ Time Frame: Day 4, 5, 8 of the 1st cycle; pre-dose (0 hour) ] [ Designated as safety issue: No ]
  • Frequency and severity of Adverse Events (AEs) [ Time Frame: Participants will be followed for the duration of treatment, an expected average of 6 months ] [ Designated as safety issue: Yes ]
    Safety will be measured in terms of type, frequency and severity of adverse events according to CTCAE v4.03.

  • Laboratory abnormalities [ Time Frame: duration of treatment, an expected average of 6 months ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: August 2012
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Panobinostat and Azacitidine
combination regimen
Drug: Panobinostat
Other Name: LBH589

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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
  2. Patient has an ECOG performance status of ≤ 2
  3. 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

Exclusion Criteria:

  1. Patient who is planned for or has history of hematopoietic stem-cell transplantation (HSCT)
  2. Patients with relapsed/refractory AML
  3. Patient is receiving concurrent anti-cancer therapy
  4. Patient has received prior treatment with deacetylase inhibitors (DACi)
  5. 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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01613976

Locations
Japan
Novartis Investigative Site
Nagoya, Aichi, Japan, 460-0001
Novartis Investigative Site
Nagoya-city, Aichi, Japan, 466-8650
Novartis Investigative Site
Kobe-city, Hyogo, Japan, 650-0017
Novartis Investigative Site
Sendai-city, Miyagi, Japan, 980-8574
Novartis Investigative Site
Chuo-ku, Tokyo, Japan, 104-0045
Novartis Investigative Site
Kyoto, Japan, 602-8566
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01613976     History of Changes
Other Study ID Numbers: CLBH589H1101
Study First Received: May 24, 2012
Last Updated: April 7, 2014
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Novartis:
Myelodysplastic Syndromes
MDS
Chronic Myelomonocytic Leukemia
CMML
Acute Myeloid Leukemia
AML
Panobinostat
LBH589
5-Aza
Azacitidine

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Myelodysplastic-Myeloproliferative Diseases
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
Azacitidine
Panobinostat
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014