Efficacy and Safety of LBH589B in Adult Patients With Refractory Chronic Myeloid Leukemia in Accelerated or Blast Phase

NCT00449761 | Terminated Phase 2 Results

• 1 other identifier: CLBH589B2211
• Study Type: interventional
• Target: 27
• Locations: 2 countries
• Sites: 26

Brief Summary

This study will evaluate the efficacy and safety of LBH589B in adult patients with chronic myeloid leukemia who are in accelerated phase or blast phase (blast crisis) with resistant disease following treatment with at least two BCR-ABL tyrosine kinase inhibitors

Conditions

Leukemia, Myeloid, Chronic

Keywords

Refractory; Chronic Myeloid; Leukemia; accelerated phase; blast phase (blast crisis); adults; oral LBH589

Outcome Measures

Primary Outcomes (1)

• Participants With Hematologic Response

  The primary efficacy variable was hematologic response, a composite endpoint defined as the overall of complete hematologic response (CHR), and of no evidence of leukemia (NEL) and of the return to chronic phase (RTC).

  From Start of the Study up to Study Termination (approximately up to 18 Months).

Secondary Outcomes (16)

• Duration of Hematologic Response

  From Start of the Study up to Study Termination (approximately up to 18 Months).

• Complete Cytogenetic Response (CCyR) Rate

  From Start of the Study up to Study Termination (approximately up to 18 Months).

• Major (Complete/Partial) Cytogenetic Response Rate

  From Start of the Study up to Study Termination (approximately up to 18 Months).

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

  From Start of the Study up to Study Termination (approximately up to 18 Months).

• Duration of Major Cytogenetic Response

  From Start of the Study up to Study Termination (approximately up to 18 Months).

Study Arms (1)

Panobinostat

EXPERIMENTAL

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

Drug: LBH589

Interventions

LBH589 DRUG

Also known as: Panobinostat

Panobinostat

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 accelerated or blast phase chronic myeloid leukemia defined as:
• Accelerated phase - the presence of at least one of the following:
• ≥15% but \<30% blasts in blood or bone marrow
• ≥30% blasts plus promyelocytes in peripheral blood or bone marrow (providing that \<30% blasts present in bone marrow)
• ≥ 20% basophiles in the peripheral blood
• Thrombocytopenia \<100 X 109 /L unrelated to sole therapy
• Blast phase (blast crisis) - the presence of one of the following:
• ≥ 30% blasts in the blood, in bone marrow or both
• Extramedullary infiltrates of leukemic cells other than liver or spleen involvement
• Prior treatment with at least two a fusion gene of the BCR and ABL genes (BCR-ABL) tyrosine kinase inhibitors (i.e., imatinib, nilotinib, or dasatinib) and demonstrated resistance to the most recent kinase inhibitor therapy. Resistance to a BCR-ABL tyrosine kinase inhibitors (TKI) for this study was defined as:
• Progression from chronic phase to either accelerated phase or blast crisis
• Progression from accelerated phase to blast crisis
• No hematologic response (defined as not achieving complete hematologic response (CHR), no evidence of leukemia (NEL) or return to chronic phase (RTC)) within 3 months of starting therapy
• Increasing blast counts in peripheral blood of increasing marrow leukemic infiltrate (MLI, the percent marrow blasts multiplied by marrow cellularity)

You may not qualify if:

• A candidate for hematopoietic stem cell transplantation
• Prior therapy with certain medications:
• Therapeutic doses of sodium warfarin or any other anti-vitamin K drug (low doses for line patency were allowed).
• Candidate for hematopoietic stem cell transplantation (HSCT)
• Prior histone deacetylase (HDAC) inhibitor treatment of Chronic Myelogenous Leukemia (CML)
• Concomitant use of drugs with a risk of causing QT complex (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 (within 3 weeks), immunotherapy (within 1 week), BCR-ABL kinase inhibitor ≤ 1 week of first treatment with panobinostat
• Patients who are in chronic phase chronic myeloid leukemia
• Impaired cardiac function or clinically significant cardiac diseases
• Concomitant use of drugs with a risk of possible risk of causing QTc prolongation or torsades de pointes
• Concomitant use of certain medications
• Impairment of Gastrointestinal (GI) function or GI disease
• Patients with unresolved diarrhea
• Women who are pregnant or breast feeding or women of childbearing potential not using an effective method of birth control

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (26)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

University of Colorado Health Sciences Center/Anschutz Cancer Pavilion

Aurora, Colorado, 80010, United States

Location

Rocky Mountain Cancer Center

Denver, Colorado, 80218, United States

Location

Northwestern University Clinical Research Office

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University Chicago Hospital

Chicago, Illinois, 60637, United States

Location

Indiana Blood and Marrow Institute/St. Francis Hospital

Beech Grove, Indiana, 46107, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Hackensack University Medical Center/Oncology Research Dept.

Hackensack, New Jersey, 07601, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Duke University Hospital

Durham, North Carolina, 27710, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Emory University School of Medicine-Winship Cancer Institute

Nashville, Tennessee, 37212, United States

Location

Vanderbilt University Medical Center, Clinical Trials Center

Nashville, Tennessee, 37212, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

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

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia; Blast Crisis

Interventions

Panobinostat

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes

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 Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

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

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 21, 2007
• Study Start: February 23, 2007
• Primary Completion: January 29, 2008
• Study Completion: August 26, 2008
• Last Updated: July 15, 2021
• Results First Posted: July 14, 2021

Record last verified: 2021-07

Locations

US (19); DE (7)