LBH589 in Refractory Myelodysplastic Syndromes (MDS)

NCT00594230 | Terminated Phase 2 Results

• 1 other identifier: SCRI MDS 07
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 7

Brief Summary

This will be a single arm Phase II study.

Conditions

Myelodysplastic Syndromes (MDS)

Keywords

Myelodysplastic Syndromes (MDS); Refractory; LBH589

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (CR, Marrow CR + PR) of LBH in Patients With Relapsed or Refractory MDS.

  Overall response rate (ORR) is defined by the modified International Working Group (IWG) Response Criteria for MDS. In the marrow, Complete Response (CR) is \<= 5% blasts present with normal maturation of all cell lines. In peripheral blood, CR is defined as hemoglobin \>= 11 g/dL, ANC \>= 1000/mL, and platelets \>= 100,000 with 0% blasts present. Partial Response (PR) is defined the same as CR with blasts decreased by \>= 50% and \>= 5% blasts in the marrow.

  Every 8 weeks up to 24 months on-study.

Secondary Outcomes (6)

• Time to Disease Progression

  Every 8 weeks up to 24 months on-study, every 3 months in follow-up until progression of disease

• Hematologic Improvement, Including Transfusion Independence

  Every 8 weeks up to 24 months on-study

• Duration of Response

  Every 8 weeks up to 24 months on-study

• Median Time to Treatment Failure

  24 months

• Median Overall Survival

  24 months on-study, patients followed every 3 months in follow-up

Study Arms (2)

Panobinostat 20 mg

EXPERIMENTAL

Treatment with LBH589 (Panobinostat) 20 mg

Drug: Panobinostat

Panobinostat 30 mg

EXPERIMENTAL

Treatment with LBH589 (Panobinostat) 30 mg

Drug: Panobinostat

Interventions

Panobinostat DRUG

Panobinostat(20 mg or 30 mg PO) will be administered three times a week on Monday, Wednesday and Friday. Treatment will be given over 21 days followed by a 7 day rest period and repeated every 28 days. Patients will be assessed for toxicity on an ongoing basis and disease assessment will be determined every 2 treatment cycles (8 weeks). Patients will be allowed to continue on treatment for a maximum of eight four week treatment cycles. Treatment will be discontinued if there is evidence of disease progression, unacceptable toxicity and/or at the discretion of the investigator.

Also known as: LBH589

Panobinostat 20 mg; Panobinostat 30 mg

Eligibility Criteria

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

You may qualify if:

• Histologically or cytological documented diagnosis of myelodysplastic syndrome (MDS).
• Male or female patients aged \>= 18 years old.
• MDS patients who have failed hypomethylating (azacitidine or decitabine) therapy.
• Patients with 5q-cytogenic abnormalities must also have progressed on or been intolerant to lenalidomide.
• Patients with up to and including 30% blasts (FAB RAEB-T) will be eligible to enroll.
• CMML with \>= 5% blasts will be eligible to enroll.
• ECOG PS 0, 1 or 2.
• Laboratory values must be as follows:
• Bilirubin \<= 1.5 mg/dL AST/SGOT \<= 2.5 x ULN ALT/SGPT Creatinine \<= 2.0 mg/dL or 24-hour Creatinine Clearance \>= 50 ml/min Albumin \>= 3 g/dL Potassium \>= lower limit normal (LLN) Phosphorous \>= LLN Calcium \>= LLN Magnesium \>= LLN
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to start of treatment.
• Life expectancy \>= 12 weeks.

You may not qualify if:

• Prior treatment with an HDAC inhibitor.
• Prior intensive chemotherapy or high dose ara-C (\>= 1 gm/m2)
• More than one prior single agent chemotherapy regimen. Prior hydroxyurea for cytoreduction will be permitted however.
• Impaired cardiac function
• Active CNS disease, including leptomeningeal metastases.
• Unresolved diarrhea \> CTCAE grade 1.
• Chemotherapy, investigational drug therapy, major surgery \< 4 weeks prior to starting study drug or patients that have not recovered from side effects of previous therapy.
• Patient is \< 5 years free of another primary malignancy except if the other primary malignancy is not currently clinically significant or requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
• Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not willing to use a double barrier method of contraception during the study and 3 months after the end of treatment. One of these methods of contraception must be a barrier method.
• Male patients whose sexual partners are WOCBP not using a double method of contraception during the study and 3 months after the end of treatment. One of these methods must be a condom.
• Patients with gastrointestinal (GI) tract disease, causing the inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis).
• Other concurrent severe, uncontrolled systemic fungal, bacterial, viral or other infection or intercurrent illness, including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients with uncontrolled coagulopathy.
• Abnormal thyroid function (TSH or free T4) detected at screening. Patients with known hypothyroidism who are stable on thyroid replacement are eligible.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (7)

Florida Cancer Specialists

Fort Myers, Florida, 33901, United States

Location

Northeast Georgia Medical Center

Gainesville, Georgia, 30501, United States

Location

Consultants in Blood Disorders and Cancer

Louisville, Kentucky, 40207, United States

Location

Center for Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

Oncology Hematology Care

Cincinnati, Ohio, 45242, United States

Location

Chattanooga Oncology Hematology Associates

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37023, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Panobinostat

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Results of a planned interim analysis demonstrated that the regimen did not demonstrate sufficient evidence of efficacy necessary to justify further enrollment. Per protocol, the results of this analysis led to early termination of the study.

Results Point of Contact

• Title: John Hainsworth, MD
• Organization: Sarah Cannon Research Institute

ASKSARAH@scresearch.net

1-877-691-7274

Study Officials

• Ian W. Flinn, M.D.

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2007
• First Posted: January 15, 2008
• Study Start: January 1, 2008
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: November 22, 2021
• Results First Posted: December 19, 2012

Record last verified: 2021-11

Locations

US (7)