Clinical Trials /

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

NCT03256045

Description:

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.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Panobinostat, Carfilzomib, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
  • Official Title: CLBH589DUS108T: Panobinostat With Carfilzomib and Dexamethasone for Relapsed/Refractory Multiple Myeloma: Correlation With In Vitro Chemosensitivity Testing

Clinical Trial IDs

  • ORG STUDY ID: 9757
  • SECONDARY ID: NCI-2017-00453
  • SECONDARY ID: 9757
  • SECONDARY ID: P30CA015704
  • SECONDARY ID: RG1016013
  • NCT ID: NCT03256045

Conditions

  • Recurrent Plasma Cell Myeloma
  • Refractory Plasma Cell Myeloma

Interventions

DrugSynonymsArms
CarfilzomibKyprolis, PR-171Treatment-panobinostat, carfilzomib, dexamethasone,chemo assay
DexamethasoneAacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, VisumetazoneTreatment-panobinostat, carfilzomib, dexamethasone,chemo assay
PanobinostatFaridak, Farydak, LBH589Treatment-panobinostat, carfilzomib, dexamethasone,chemo assay

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To correlate in vitro drug sensitivity testing with clinical response by determining the
      rate of in vitro drug sensitivity to panobinostat, carfilzomib, and dexamethasone singly and
      in combination, doublets and triplets.

      SECONDARY OBJECTIVES:

      I. To monitor response rates (partial response [PR], very good partial response [VGPR], and
      complete response) using the International Myeloma Working Group Uniform Response Criteria
      for Multiple Myeloma.

      EXPLORATORY OBJECTIVES:

      I. Progression free survival and overall survival will be assessed for up to 3 years after
      last dose.

      OUTLINE:

      Patients receive panobinostat orally (PO) on days 1, 3, 5, 15, 17, and 19. Patients also
      receive carfilzomib intravenously (IV) and dexamethasone PO on days 1, 2, 8, 9, 15, and 16.
      Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or
      unacceptable toxicity. Patients also undergo collection of blood and/or bone marrow samples
      for testing via in vitro chemosensitivity assay.

      After completion of study treatment, patients are followed up every 3 months for up to 3
      years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment-panobinostat, carfilzomib, dexamethasone,chemo assayExperimentalPatients receive panobinostat PO on days 1, 3, 5, 15, 17, and 19. Patients also receive carfilzomib IV and dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and/or bone marrow samples for testing via in vitro chemosensitivity assay.
  • Carfilzomib
  • Dexamethasone
  • Panobinostat

Eligibility Criteria

        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 hour (hr)

          -  Absolute neutrophil count (ANC) >= 750/uL

          -  Platelet count >= 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

          -  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

          -  Women of child-bearing potential, defined as all women physiologically capable of
             becoming pregnant, should have a pregnancy test prior to the initiation of treatment
             and use highly effective methods of contraception during and for 3 months post study
             treatment; highly effective contraception methods include total abstinence, female
             sterilization, male sterilization, use of oral, injected, or implanted hormonal
             methods of contraception or placement of an intrauterine device (IUD) or intrauterine
             system (IUS) or other forms of hormonal contraception that have comparable efficacy;
             women using hormonal contraceptives should additionally use a barrier method of
             contraception; women are considered post-menopausal and not of child-bearing potential
             if they have had 12 months of natural amenorrhea or have had surgical bilateral
             oophorectomy (with or without hysterectomy), total hysterectomy, or tubal ligation at
             least 6 weeks ago

          -  Sexually active males must use a condom during intercourse while taking study drug and
             for 6 months after stopping treatment; males should not father a child in this period;
             a condom is required to be used also by vasectomized men as well as during intercourse
             with a male partner; female partners of sexually active men should also use an
             effective contraception during treatment and for 6 months after their male partner has
             stopped taking the drug

        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 randomization 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 have known or definite risk of prolonging the QT
             interval or inducing Torsades de pointes (TdP); the medication must be discontinued or
             switched to a safe alternative medication prior to starting treatment; specific
             exception is allowed for patients on long-standing medications that have risk of
             prolonging QT interval or inducing TdP if screening electrocardiography (ECG) does not
             indicate a prolonged QT abnormality

          -  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 side effects of surgery
             that have not recovered to < CTCAE grade 2
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Partial response rate
Time Frame:Up to 3 years after last study treatment
Safety Issue:
Description:Assessed using the International Myeloma Working Group Uniform Response Criteria for Multiple Myeloma.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Washington

Last Updated

June 7, 2019