Efficacy and Safety of LBH589 in Adult Patients With Refractory Chronic Myeloid Leukemia (CML) in Chronic Phase

NCT00451035 | Terminated Phase 2 Results

• 1 other identifier: CLBH589B2202
• Study Type: interventional
• Target: 29
• Locations: 2 countries
• Sites: 10

Brief Summary

This study will evaluate the efficacy and safety of LBH589B in adult patients with chronic phase chronic myeloid leukemia with resistant disease following treatment with at least two BCR-ABL tyrosine kinase inhibitors

Conditions

Chronic Myeloid Leukemia in Chronic Phase

Keywords

Refractory Chronic Myeloid Leukemia in Chronic Phase; adults; oral LBH589

Outcome Measures

Primary Outcomes (1)

• Major (Complete/Partial) Cytogenetic Response (MCyR) Rate

  The CyR, based on the percentage of Ph+ metaphases by karyotype analysis on a bone marrow aspirate, was ideally assessed from a minimum of 20 metaphases in each bone marrow sample. The CyR was defined as: major response including complete (CCyR; 0% Ph+ metaphases) or partial (PCyR; 1 to 35% Ph+ metaphases), minor (36 to 65% Ph+ metaphases), minimal (66 to 95% Ph+ metaphases) or none (96 to 100% Ph+ metaphases).

  From Start of the Study up to End of Study (approximately up to 19 Months)

Secondary Outcomes (13)

• Duration of Major (Complete/Partial) Cytogenetic Response (MCyR) Rate

  From Start of the Study up to End of Study (approximately up to 19 Months)

• Complete Hematologic Response (CHR) Rate

  From Start of the Study up to End of Study (approximately up to 19 Months)

• Complete Cytogenetic Response (CCyR) and Overall (Complete/Partial/Minor/Minimal) Cytogenetic Response (OCyR) Rates

  From Start of the Study up to End of Study (approximately up to 19 Months)

• Major (MMR) and Complete (CMR) Molecular Response Rates

  From Start of the Study up to End of Study (approximately up to 19 Months)

• BCR-ABL Mutations of Participants at Study Entry and, in Responding Participants and at the Time of Disease Progression

  From Start of the Study up to End of Study (approximately up to 19 Months)

Study Arms (1)

Panobinostat (LBH589)

EXPERIMENTAL

Participants were administered panobinostat 20 milligram (mg) orally once a day (OD) three times a week as part of a 4 week (28 day) treatment cycle. Panobinostat were administered at the same time each morning with 8oz/240 milliliter (ml) of water after a fasting period of at least two hours (water was allowed). Participants could continue treatment until they experienced unacceptable toxicity or disease progression.

Drug: LBH589

Interventions

LBH589 DRUG

Also known as: Panobinostat

Panobinostat (LBH589)

Eligibility Criteria

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

You may qualify if:

• Male or female patients aged ≥ 18 years old
• Diagnosis of Philadelphia chromosome positive, chronic phase chronic myeloid leukemia
• Prior treatment with at least two BCR-ABL tyrosine kinase inhibitors with demonstrated resistance to the most recent kinase inhibitor therapy.
• Patients with a history of intolerance to one BCR-ABL kinase inhibitors will be considered eligible to enter the study if they demonstrate resistance to their most recent BCR-ABL kinase inhibitor.
• Patients who are intolerant of at least 2 BCR-ABL kinase inhibitors will be considered eligible to enter this study if they also demonstrate resistance to or intolerance of interferon-alpha (IFN-α) by the same criteria defined above.
• Patients must have adequate laboratory values:
• Hematology: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, hemoglobin ≥ 8.0 g/dL.
• Serum chemistry: albumin ≥ 3 g/dL; aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) ≤ 2.5 x upper limit of normal (ULN) or ≤ 5.0 x ULN if the transaminase elevation is due to leukemic involvement; bilirubin ≤ 1.5 x ULN; creatinine ≤ 1.5 x ULN or 24-hour creatinine clearance ≥ 50 mL/min; potassium, phosphorus, magnesium and total calcium (corrected for serum albumin) or serum ionized calcium ≥ lower limit of normal (LLN), thyroid stimulating hormone (TSH) and free T4 (thyroxine) within normal limits.
• Note: Potassium, calcium, and magnesium supplements to correct values that are \< LLN, were allowed when documented as corrected prior to enrollment.
• Baseline measurement of left ventricular ejection fraction \[assessment of the hearts ability to pump effectively\]
• Assessment of patients ability to perform every day activities. Assessment by the Eastern Cooperative Oncology Group (ECOG) Performance Status

You may not qualify if:

• A candidate for hematopoietic stem cell transplantation
• Prior therapy with certain medications
• Patients with a prior history of accelerated phase or blast crisis CML
• Impaired cardiac function or clinically significant cardiac diseases
• Concomitant use of certain medications. Therapeutic doses of sodium warfarin or any other anti-vitamin K drug (low doses for line patency were allowed). Prior HDACi treatment of CML, concomitant use of drugs with a risk of causing QT interval (QTc) prolongation or torsades de pointes, CYP3A4/5 inhibitors, anti-cancer therapy or radiation therapy, valproic acid (within 5 days prior to study drug treatment or during the study), chemotherapy or major surgery (within 3 weeks), immunotherapy (within 1 week), BCR-ABL tyrosine kinase inhibitors (TKI) ≤ 1 week of first treatment with panobinostat
• Impairment of GI function or GI disease
• Patients with unresolved diarrhea
• Patients who have received chemotherapy, any investigational drugs or undergone major surgery \< 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
• Patients who have received a BCR-ABL tyrosine-kinase inhibitor within 1 week of first treatment with LBH589
• Women who are pregnant or breast feeding or women of childbearing potential not using an effective method of birth control
• Male patients whose sexual partners are women of child bearing potential not using effective birth control

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (10)

Novartis Investigative Site

Brussels, Belgium

Location

Novartis Investigative Site

Godinne, Belgium

Location

Novartis Investigative Site

Leuven, Belgium

Location

Novartis Investigative Site

Cologne, Germany

Location

Novartis Investigative Site

Düsseldorf, Germany

Location

Novartis Investigative Site

Hamburg, Germany

Location

Novartis Investigative Site

Leipzig, Germany

Location

Novartis Investigative Site

Mainz, Germany

Location

Novartis Investigative Site

Mannheim, Germany

Location

Novartis Investigative Site

Munich, Germany

Location

Related Publications (1)

• Savelieva M, Woo MM, Schran H, Mu S, Nedelman J, Capdeville R. Population pharmacokinetics of intravenous and oral panobinostat in patients with hematologic and solid tumors. Eur J Clin Pharmacol. 2015 Jun;71(6):663-672. doi: 10.1007/s00228-015-1846-7. Epub 2015 May 5.

  PMID: 25939707 RESULT

MeSH Terms

Interventions

Panobinostat

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Novartis pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticlas

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2007
• First Posted: March 22, 2007
• Study Start: February 19, 2007
• Primary Completion: April 13, 2008
• Study Completion: September 30, 2008
• Last Updated: July 15, 2021
• Results First Posted: July 14, 2021

Record last verified: 2021-07

Locations

DE (7); BE (3)