Phase I Study of Panobinostat + Bortezomib for Relapsed and/or Refractory Mantle Cell Lymphoma (MCL) (BUS48T)

This study has been completed.
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Anand Jillella, Georgia Regents University
ClinicalTrials.gov Identifier:
NCT01504776
First received: August 8, 2011
Last updated: September 18, 2014
Last verified: January 2012
  Purpose

The purpose of this study is to determine the safety and clinical efficacy of the combination of panobinostat plus bortezomib.


Condition Intervention Phase
Mantle Cell Lymphoma
Drug: Panobinostat
Drug: Bortezomib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Panobinostat in Combination With Bortezomib in the Treatment of Relapsed and/or Refractory Mantle Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by Georgia Regents University:

Primary Outcome Measures:
  • Dose-Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD) [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    To determine the DLTs and MTD of panobinostat given in combination with bortezomib.


Secondary Outcome Measures:
  • Observe the activity of the combination against Mantle Cell Lymphoma (MCL) in patients treated in this Phase I study. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

    Pre-treatment primary MCL cells derived from the bone marrow and/or peripheral blood of patients enrolled in this clinical trial will be isolated and treated ex vivo with panobinostat and/or bortezomib. IC50 values for each agent, as well as the combination indices values for the two agents will be determined and correlated with clinical response.

    Pre-treatment and 24 hour post-treatment primary MCL cells from patients who have circulating MCL cells in the peripheral blood will be isolated, as above.



Enrollment: 3
Study Start Date: April 2011
Study Completion Date: September 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Open Label Drug Therapy
Single arm
Drug: Panobinostat
Dose escalation study of oral panobinostat administered Monday-Wednesday-Friday (MWF) weekly x 4 weeks, utilizing 3+3 dosing scheme (15, 20, 25 mg) in combination with a fixed dose of bortezomib 1.3 mg/m2 administered as a short intravenous (IV)infusion of 3-5 seconds every week x 4 weeks, representing one cycle. Each week, bortezomib will be administered IV prior to the oral dose of panobinostat
Other Name: LBH589
Drug: Bortezomib

Detailed Description:

This is a phase I single arm, open label, multi-center (3 participating sites) dose escalation study of oral panobinostat administered Monday-Wednesday-Friday (MWF) weekly x 4 weeks, utilizing 3+3 dosing scheme (15, 20, 25 mg) in combination with a fixed dose of bortezomib 1.3 mg/m2 administered as a short intravenous (IV) infusion of 3-5 seconds every week x 4 weeks, representing one cycle. Each week, bortezomib will be administered IV prior to the oral dose of panobinostat. There will be sub-investigators participating in this study who will enroll at sub-sites.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients aged ≥ 18 years old
  • Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
  • Patients must have adequate hematology/chemistry lab values
  • Echocardiogram (ECHO) must demonstrate Left Ventricular Ejection Fraction (LVEF) ≥ 50%.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
  • Patients with previously diagnosed MCL based on standard criteria and with at least one and a maximum of 4 lines of therapy and currently requiring further treatment
  • Prior therapy with autologous and allogeneic stem cell transplant is permissible. Patients who have undergone an allogeneic transplant should have no evidence of graft-versus-host disease (GVHD) and should not be on any immunosuppressive therapy. Autologous and allogeneic transplant will be counted as one prior therapy.
  • Patients previously treated with bortezomib will be included in the study

Exclusion Criteria:

  • Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer
  • Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first LBH589 (Panobinostat) treatment
  • Peripheral neuropathy ≥ Common Toxicity Criteria for Adverse Effects (CTCAE) grade 2 on clinical examination within 14 days of randomization
  • Impaired cardiac function or clinically significant cardiac diseases
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of LBH589
  • Patients with diarrhea > CTCAE grade 2.
  • Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes or active or uncontrolled infection) including abnormal laboratory values, that could cause unacceptable safety risks or compromise compliance with the protocol
  • Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug
  • Patients who have received targeted agents within 2 weeks or within 5 half-lives of the agent and active metabolites (whichever is longer) and who have not recovered from side effects of those therapies.
  • Patients who have received either immunotherapy within < 8 weeks; chemotherapy within < 4 weeks; or radiation therapy to > 30% of marrow-bearing bone within < 2 weeks prior to starting study treatment; or who have not yet recovered from side effects of such therapies.
  • Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  • Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not using an effective method of birth control. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). Women of childbearing potential must have a negative serum pregnancy test within 24hrs of receiving the first dose of study medication.
  • Male patients whose sexual partners are WOCBP not using effective birth control
  • Patients with a prior malignancy within the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix)
  • Patients with known positivity for human immunodeficiency virus (HIV) ) or hepatitis C; baseline testing for HIV and hepatitis C is not required
  • Patients with any significant history of non-compliance to medical regimens or unwilling or unable to comply with the instructions given to him/her by the study staff.
  • Allergic reaction to bortezomib
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01504776

Locations
United States, Georgia
Georgia Regents University
Augusta, Georgia, United States, 30912
Sponsors and Collaborators
Anand Jillella
Novartis Pharmaceuticals
Investigators
Principal Investigator: Anand Jillella, MD Georgia Regents University
  More Information

No publications provided

Responsible Party: Anand Jillella, Chief, Hematology/Oncology, Georgia Regents University
ClinicalTrials.gov Identifier: NCT01504776     History of Changes
Other Study ID Numbers: CLBH589BUS48T
Study First Received: August 8, 2011
Last Updated: September 18, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Georgia Regents University:
MCL
Lymphoma
Panobinostat

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Bortezomib
Panobinostat
Antineoplastic Agents
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014