Panobinostat, Carfilzomib and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

Overview

This phase II trial studies how well panobinostat, carfilzomib and dexamethasone work in treating patients with multiple myeloma that has come back or does not respond to treatment.

Panobinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carfilzomib and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Using multiple myeloma cells from patients' blood samples, the researchers will do laboratory tests to look at how well each of the drugs, alone and in different combinations, kill multiple myeloma cells. If the laboratory tests work well, they may be used in the future to help plan treatment for future patients.

SparkCures ID 901
Trial Phase Phase 2
Enrollment 40 Patients
Treatments
Trial Sponsors
  • Fred Hutchinson Cancer Research Center
Trial Collaborators
  • National Cancer Institute (NCI)
NCT Identifier

NCT03256045

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:

  • Diagnosis of multiple myeloma refractory to or relapsed after >= 1 line of prior therapy (International Myeloma Working Group [IMWG] criteria)
  • Measurable disease, as indicated by one of the following:
    • Serum monoclonal (M)-protein >= 1.0 g/dL
    • Elevated free light chain as per IMWG criteria, and abnormal ratio
    • Urine Bence Jones protein > 200 mg/24 hr
  • Absolute neutrophil count (ANC) of >= 1,000/uL
  • Platelet count of >= 75,000/uL
  • Hemoglobin >= 7 g/dL
  • Creatinine =< 2.0 mg/dL or calculated creatinine clearance >= 30 mL/min
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) unless elevation is thought to be due to Gilbert's syndrome
  • Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SPGT) (alanine aminotransferase [ALT]) =< 2.5 x ULN
  • The following laboratory values must be, or corrected to with supplements, over the lower limit of normal before starting treatment:
    • Serum sodium
    • Potassium
    • Magnesium
    • Phosphorus
  • Patients must avoid consumption of grapefruit, pomegranates, starfruit, Seville oranges or products containing the juice of each during the entire study and preferably 7 days before the first dose of study medications; orange juice is allowed

Exclusion Criteria:

  • Another bone marrow malignancy
  • Another cancer with expected survival of < 2 years
  • Active viral, bacterial, or fungal infection progressing on current treatment
  • Clinically significant uncontrolled heart disease and/or recent cardiac event within 6 months prior to enrollment, such as:
    • History of angina pectoris, symptomatic pericarditis, or myocardial infarction
    • Left ventricular ejection fraction (LVEF) < 45% as determined by echocardiogram (ECHO) or multi gated acquisition (MUGA) scan
    • History or presence of any significant, uncontrolled, or persistent cardiac arrhythmias, e.g. ventricular, supraventricular, nodal arrhythmias or conduction abnormality; stable atrial fibrillation within 6 months prior to enrollment is permitted
    • Presence of unstable atrial fibrillation (ventricular response rate > 100 beats per minute [bpm]); NOTE: patients with stable atrial fibrillation can be enrolled provided they do not meet other cardiac exclusion criteria
    • Resting heart rate < 50 bpm
    • Complete left bundle branch block (LBBB), bifascicular block
    • Congenital long QT syndrome
    • Any clinically significant ST segment and/or T-wave abnormalities
    • Corrected QT (QTcF) > 450 msec for males and females using Fridericia's correction on screening electrocardiogram (ECG) by mean value of triplicate ECGs
    • History of documented congestive heart failure (New York Heart Association functional classification III-IV)
    • Uncontrolled hypertension defined by a systolic blood pressure (SBP) >= 150 mmHg and/or diastolic blood pressure (DBP) >= 100 mmHg with or without antihypertensive medication; NOTE: initiation or adjustment of antihypertensive medication(s) is allowed prior to screening
    • Other clinically significant heart disease or vascular disease
  • Currently taking medications that risk prolonging the QT interval or inducing Torsades de pointes; the medication must be discontinued or switched to a safe alternative medication prior to starting treatment
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat or dexamethasone (e.g. ulcerative disease uncontrolled nausea, vomiting, malabsorption syndrome, obstruction, or stomach and/or small bowel resection)
  • Unresolved diarrhea >= Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or a medical condition associated with chronic diarrhea (such as irritable bowel syndrome, inflammatory bowel disease)
  • Major surgery =< 14 days prior to starting study treatment or who have not recovered from side effects to < grade 2 CTCAE
  • 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 anytime in the proceeding 12 consecutive months); women of childbearing potential must have a negative serum pregnancy test within 24 hrs of receiving the first dose of study medication
  • Male patients whose sexual partners are WOCBP not using effective birth control

US Trial Locations

Accepting Patients

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

Washington

Resources

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