Panobinostat Combined With High-Dose Gemcitabine/Busulfan/Melphalan With Autologous Stem Cell Transplant for Patients With Refractory/Relapsed Myeloma

Overview

The goal of this clinical research study is to learn if a combination of panobinostat, gemcitabine, busulfan, and melphalan and a stem cell transplant can help to control MM. The safety of this combination will also be studied.

This is an investigational study. Panobinostat and melphalan are FDA approved for the treatment of MM. Busulfan is FDA approved for the treatment of leukemia. Gemcitabine is FDA approved for the treatment of lymphoma, breast cancer, and lung cancer. The use of these study drugs in combination is investigational. The study doctor can explain how the study drugs are designed to work.

Up to 80 participants will take part in this study. All will be enrolled at MD Anderson.

SparkCures ID 746
Trial Phase Phase 2
Enrollment 80 Patients
Treatments
Trial Sponsors
  • MD Anderson Cancer Center
Trial Collaborators
  • Novartis
NCT Identifier

NCT02506959

Am I Eligible?

The following criteria is a partial list of reasons why patients may or may not be eligible to participate in this clinical trial. Further evaluation with a medical professional will be required to determine full eligibility.

The following criteria is provided for health care professionals.

Inclusion Criteria:

  • Refractory or relapsed myeloma, defined as one or more of the following:
    • Treated with first-line therapy including at least 2 cycles of lenalidomide, bortezomib or thalidomide, and one or more of the following:
      • Less than partial response (PR) to first-line therapy
      • Relapse after first (1st) line therapy
    • High-risk cytogenetics, defined by deletion (del)(13q) by conventional cytogenetics, or by del(17p), t(4;14), t(14;16), t(14;20) or 1q+ by fluorescence in situ hybridization (FISH)
    • Relapse after a prior autologous stem cell transplant (ASCT)
    • Plasma cell leukemia
    • Soft tissue plasmacytoma
  • Serum creatinine =< 1.8 mg/dL and/or estimated serum creatinine clearance >= 50 ml/min
  • Serum glutamic oxaloacetic transaminase (SGOT) and/or serum glutamate pyruvate transaminase (SGPT) =< 3 x upper limit of normal
  • Serum bilirubin =< 2 x upper limit of normal, unless proven to be due to disease involvement
  • Alkaline phosphatase =< 2 x upper limit of normal, unless proven to be due to disease involvement
  • Adequate pulmonary function with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO) >= 50% of expected corrected for hemoglobin and/or volume
  • Adequate cardiac function with left ventricular ejection fraction >= 40%
  • No uncontrolled arrhythmias or symptomatic cardiac disease
  • Clinically euthyroid; note: patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism
  • Zubrod performance status < 2
  • Negative beta-human chorionic gonadotropin (HCG) test in a woman of child-bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization
  • Availability of >= 2.5 million cluster of differentiation (CD)34+ cells/kg previously apheresed
  • Ability to provide written informed consent

Exclusion Criteria:

  • Prior whole brain irradiation
  • Having received radiation therapy to head and neck (excluding eyes), and internal organs of chest, abdomen or pelvis in the month prior to enrollment
  • Active hepatitis B, either active carrier (hepatitis B surface antigen positive [HBsAg +]) or viremic (hepatitis B virus [HBV] deoxyribonucleic acid [DNA] >= 10,000 copies/mL, or >= 2,000 IU/mL)
  • Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic hepatitis C or positive hepatitis C serology
  • Active infection requiring parenteral antibiotics
  • Known positivity for human immunodeficiency virus (HIV)
  • Autologous stem-cell transplant in the previous six months
  • Needing valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat
  • 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
  • Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:
    • History or presence of sustained ventricular tachyarrhythmia; (patients with a history of atrial arrhythmia are eligible but should be discussed with Novartis prior to enrollment)
    • Any history of ventricular fibrillation or torsade de pointes
    • Bradycardia defined as heart rate (HR) < 50 beats per minute (bpm); patients with pacemakers are eligible if HR >= 50 bpm
    • Screening electrocardiogram (ECG) with a corrected QT (QTc) > 470 msec
    • Right bundle branch block + left anterior hemiblock (bifascicular block)
    • Myocardial infarction or unstable angina =< 12 months prior to starting study drug
    • Other clinically significant heart disease (e.g., congestive heart failure [CHF] New York [NY] Heart Association class III or IV , uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
  • Have undergone major surgery =< 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  • Prior malignancy with in the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix)
  • 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
  • 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
  • Having received immunotherapy or chemotherapy within 2 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
  • Grade >= 3 nonhematological toxicity from prior therapy that has not resolved to =< grade 1

US Trial Locations

Accepting Patients

The following is a listing of trial locations that are open and accepting patients.

Texas

Resources

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