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

Stopped early · Phase 2

Conditions studied: Leukemia, Myeloid, Chronic

In brief

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

Key facts

Study ID

NCT00449761

Run by

Novartis Pharmaceuticals

People needed

27

Starts

2007-02-23

Expected to finish

2008-08-26

Last updated by the study team

2021-07-15

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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)
• Patients with a history of intolerance to one BCR-ABL kinase inhibitors (defined as discontinuation of treatment due grade 3 or 4 adverse events related to treatment) will be considered eligible to enter the study if they demonstrate resistance to their most recent BCR-ABL kinase inhibitor. Intolerance was defined as discontinuation of treatment due to either grade 3 or 4 treatment-related Adverse Event (AE) or a grade 2 treatment-related AE persisting for ≥ one month or recurring more than three times despite dose reduction.
• Patients must have adequate laboratory values:
• Serum albumin ≥ 3g/dL
• Aspartate Aminotransferase (AST)/Serum Glutamate Oxalacetate Transaminase (SGOT) and Alanine Aminotransferase (ALT)/Serum Glutamate Pyruvate Transaminase (SGPT) ≤ 2.5 x upper limit of normal (ULN) or ≤ 5.0 x ULN if the transaminase elevation is due to leukemic involvement
• Serum bilirubin ≤ 1.5 x ULN
• Serum creatinine ≤ 1.5 x ULN or 24-hour creatinine clearance ≥ 50 ml/min
• Serum potassium, phosphorus, magnesium, and serum total calcium (corrected for serum albumin) or serum ionized calcium ≥ Lower Limit of Normal (LLN). Supplementation was allowed to correct potassium, calcium, and magnesium values prior to enrollment.
• Thyroid Stimulating Hormone (TSH) and free Thyroxine (T4) within normal limits (WNL) (patients may have been on thyroid hormone replacement)
• 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 of ≤ 2.

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
• Male patients whose sexual partners are women of child bearing potential not using effective birth control Other protocol-defined inclusion/exclusion criteria may apply

Where it is running

• City of Hope National Medical Center — Duarte, California, United States
• University of Colorado Health Sciences Center/Anschutz Cancer Pavilion — Aurora, Colorado, United States
• Rocky Mountain Cancer Center — Denver, Colorado, United States
• Northwestern University Clinical Research Office — Chicago, Illinois, United States
• Rush University Medical Center — Chicago, Illinois, United States
• University Chicago Hospital — Chicago, Illinois, United States
• Indiana Blood and Marrow Institute/St. Francis Hospital — Beech Grove, Indiana, United States
• University of Michigan — Ann Arbor, Michigan, United States
• Mayo Clinic Cancer Center — Rochester, Minnesota, United States
• Hackensack University Medical Center/Oncology Research Dept. — Hackensack, New Jersey, United States
• Roswell Park Cancer Institute — Buffalo, New York, United States
• University of Rochester Medical Center — Rochester, New York, United States
• Duke University Hospital — Durham, North Carolina, United States
• Wake Forest University Health Sciences — Winston-Salem, North Carolina, United States
• Oregon Health & Science University — Portland, Oregon, United States
• Emory University School of Medicine-Winship Cancer Institute — Nashville, Tennessee, United States
• Vanderbilt University Medical Center, Clinical Trials Center — Nashville, Tennessee, United States
• University of Texas Southwestern Medical Center — Dallas, Texas, United States
• Seattle Cancer Care Alliance — Seattle, Washington, United States
• Novartis Investigative Site — Cologne, Germany
• Novartis Investigative Site — Düsseldorf, Germany
• Novartis Investigative Site — Hamburg, Germany
• Novartis Investigative Site — Leipzig, Germany
• Novartis Investigative Site — Mainz, Germany
• Novartis Investigative Site — Mannheim, Germany

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.