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

NCT01613976 | Completed Phase 1

• 1 other identifier: CLBH589H1101
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 6

Brief 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).

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; 5-Aza; Azacitidine

Outcome Measures

Primary Outcomes (1)

• Incidence of Dose Limiting Toxicitiy(DLT)

  DLT will be assessed during PK run-in period (up to 7 days) and 1st cycle (28 days)

  first 5 weeks of treatment period

Secondary Outcomes (8)

• PK parameter - Cmax

  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

  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)

  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)

  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

  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

Study Arms (1)

Panobinostat and Azacitidine

EXPERIMENTAL

combination regimen

Drug: Panobinostat

Interventions

Panobinostat DRUG

Also known as: LBH589

Panobinostat and Azacitidine

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• \. 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (6)

Novartis Investigative Site

Nagoya, Aichi-ken, 460-0001, Japan

Location

Novartis Investigative Site

Nagoya, Aichi-ken, 466-8650, Japan

Location

Novartis Investigative Site

Kobe, Hyōgo, 650-0017, Japan

Location

Novartis Investigative Site

Sendai, Miyagi, 980-8574, Japan

Location

Novartis Investigative Site

Chuo-ku, Tokyo, 104-0045, Japan

Location

Novartis Investigative Site

Kyoto, 602-8566, Japan

Location

Related Publications (1)

• 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.

  PMID: 28905323 DERIVED

Related Links

• Novartis results database

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic; Leukemia, Myeloid, Acute

Interventions

Panobinostat

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2012
• First Posted: June 7, 2012
• Study Start: August 1, 2012
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: December 19, 2020

Record last verified: 2020-12

Locations

JP (6)