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

Anand Jillella

Status and phase

Completed

Phase 1

Conditions

Mantle Cell Lymphoma

Treatments

Drug: Bortezomib

Drug: Panobinostat

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01504776

CLBH589BUS48T

Details and patient eligibility

About

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

Full 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.

Enrollment

3 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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