Panobinostat (LBH589): Multiple Myeloma - Autologous Hematopoietic Cell Transplantation (HCT)

This is an interventional treatment trial for Multiple Myeloma focused on measuring autologous hematopoietic cell transplant (HCT), autologous Read More

Inclusion Criteria:

• Adult patients, age ≥ 18 years old
• Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
• Histologically confirmed diagnosis of multiple myeloma
• Meeting the Criteria for Symptomatic Multiple Myeloma (CRAB criteria) before the initiation of systemic chemotherapy
• Received high-dose melphalan (≥ 140 mg/m^2) followed by autologous HCT based on the institutional guidelines and within +45 and +180 after autologous HCT at the time of panobinostat maintenance initiation
• Must have achieved at least partial response (PR) prior to autologous HCT and must not have progressive disease (PD) prior to the initiation of maintenance therapy
• Must meet the following laboratory criteria (prior to the initiation of panobinostat maintenance): Absolute neutrophil count (ANC) ≥ 1 x 10^9/L; Hemoglobin ≥ 8 g/dl; Platelets ≥ 50 x 10^9/L (without transfusion support); Creatinine clearance ≥ 40 ml/min or serum creatinine ≤ 2.5 x upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN; Serum bilirubin ≤ 1.5 x ULN; Albumin > 3.0 g/dl; Clinically euthyroid. Note: Participants are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.
• Baseline (pre-HCT) multigated acquisition (MUGA) or echocardiogram (ECHO) must demonstrate left ventricular ejection fraction (LVEF) ≥ the limit of normal (LLN) of the institutional normal
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2 or Karnofsky performance status ≥ 70%
• Prior histone deacetylase (HDAC), deacetylase (DAC), HSP90 inhibitors or valproic acid for the treatment of cancer is allowed

Exclusion Criteria:

• Potential participants who have purely non-secretory multiple myeloma (i.e., the absence of a measurable protein in serum by electrophoresis and immunofixation and the absence of Bence-Jones protein in the urine defined by use of electrophoresis and immunofixation)
• Prior allogeneic HCT
• Prior solid organ transplant requiring immunosuppressive therapy
• Potential participants who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
• Impaired cardiac function or clinically significant cardiac diseases
• Diarrhea > Common Terminology Criteria for Adverse Events (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
• 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
• 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.
• 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
• Have undergone major surgery ≤ 4 weeks prior to starting study drug or 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 must have a negative serum pregnancy test within 24 hours of receiving the first dose of study medication.
• Male patients whose sexual partners are WOCBP not using effective birth control
• A prior malignancy with in the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix)
• Known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required
• 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