NCT02114502

Brief Summary

The goal of this clinical research study is to learn if carfilzomib and vorinostat combined with gemcitabine, busulfan, and melphalan with a stem cell transplant will help to control multiple myeloma (MM). Researchers also want to learn about the safety and effectiveness of this combination.

Trial Health

10
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 11, 2014

Completed
4 days until next milestone

First Posted

Study publicly available on registry

April 15, 2014

Completed
5 months until next milestone

Study Start

First participant enrolled

September 1, 2014

Completed
4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2018

Completed
Last Updated

July 11, 2014

Status Verified

July 1, 2014

Enrollment Period

4 years

First QC Date

April 11, 2014

Last Update Submit

July 9, 2014

Conditions

Keywords

MyelomaMultiple myelomaMMRefractoryRelapsedStem Cell TransplantSCTCarfilzomibSAHAVorinostatSuberoylanilide Hydroxamic AcidMSK-390ZolinzaGemcitabineGemcitabine HydrochlorideGemzarBusulfanBusulfexMyleranPaliferminKepivanceDexamethasoneDecadronMelphalanAlkeranCaphosolGlutamineEnterexGlutapak-10NutreStoreResourceGlutaSolveSympt-X G.I.Sympt-XPyridoxine

Outcome Measures

Primary Outcomes (1)

  • Complete Remission (CR) Rate

    Complete remission (CR) rate defined as percentage of number of complete responses in total number of patients treated.

    100 days

Secondary Outcomes (1)

  • Response Rates (RR)

    100 days

Study Arms (1)

Carfilzomib/SAHA + Gem/Bu/Mel + Auto Stem Cell Transplant SCT

EXPERIMENTAL

Busulfan test dose of 32 mg/m2 by vein on Day -10 if inpatient, on Day -12 if outpatient, then AUC of 4,000 microMol.min on Days -8 to -5. Palifermin 60 microgram/kg by vein on Days -12 to -10 and Days 0, +1 and +2. SAHA 1,000 mg by mouth on Days -8 to -3. Gemcitabine loading dose of 75 mg/m2 followed by continuous infusion of the remaining dose of 1875 mg/m2 by vein on Days -8 and -3. Carfilzomib 27 mg/m2 by vein on Days -7 and -6, then on Days -2 and -1. SAHA 1,000 mg by mouth on Days -7 to -3. Melphalan 60 mg/m2 by vein on Days -3 and -2. Stem cell transplant on Day 0. Dexamethasone 8 mg by vein twice a day from Day -9 PM to Day -2 PM. Caphosol oral rinses 30 mL four times a day from Day -9 until discharge. Oral glutamine 15 g four times a day, swished, gargled and spit on Day -9 until discharge. Pyridoxine 100 mg by vein or mouth three times a day from Day -1.

Drug: CarfilzomibDrug: SAHADrug: GemcitabineDrug: BusulfanDrug: MelphalanProcedure: Stem Cell Transplant (SCT)Drug: PaliferminDrug: DexamethasoneDrug: CaphosolDrug: GlutamineDrug: Pyridoxine

Interventions

27 mg/m2 by vein on Days -7 and -6, then on Days -2 and -1

Carfilzomib/SAHA + Gem/Bu/Mel + Auto Stem Cell Transplant SCT
SAHADRUG

1,000 mg by mouth on Days -8 to -3.

Also known as: Vorinostat, Suberoylanilide Hydroxamic Acid, MSK-390, Zolinza
Carfilzomib/SAHA + Gem/Bu/Mel + Auto Stem Cell Transplant SCT

Loading dose of 75 mg/m2 followed by continuous infusion of the remaining dose of 1875 mg/m2 by vein on Days -8 and -3.

Also known as: Gemcitabine Hydrochloride, Gemzar
Carfilzomib/SAHA + Gem/Bu/Mel + Auto Stem Cell Transplant SCT

Test dose of 32 mg/m2 by vein on Day -10 if inpatient, on Day -12 if outpatient, then AUC of 4,000 microMol.min on Days -8 to -5.

Also known as: Busulfex, Myleran
Carfilzomib/SAHA + Gem/Bu/Mel + Auto Stem Cell Transplant SCT

60 mg/m2 by vein on Days -3 and -2.

Also known as: Alkeran
Carfilzomib/SAHA + Gem/Bu/Mel + Auto Stem Cell Transplant SCT

Stem cell transplant on Day 0.

Carfilzomib/SAHA + Gem/Bu/Mel + Auto Stem Cell Transplant SCT

60 microgram/kg by vein on Days -12 to -10 and Days 0, +1 and +2.

Also known as: Kepivance
Carfilzomib/SAHA + Gem/Bu/Mel + Auto Stem Cell Transplant SCT

8 mg by vein twice a day from Day -9 PM to Day -2 PM.

Also known as: Decadron
Carfilzomib/SAHA + Gem/Bu/Mel + Auto Stem Cell Transplant SCT

30 mL oral rinse four times a day from Day -9 until discharge.

Carfilzomib/SAHA + Gem/Bu/Mel + Auto Stem Cell Transplant SCT

15 g four times a day, swished, gargled and spit on Day -9 until discharge.

Also known as: Enterex, Glutapak-10, NutreStore, Resource, GlutaSolve, Sympt-X G.I., Sympt-X
Carfilzomib/SAHA + Gem/Bu/Mel + Auto Stem Cell Transplant SCT

100 mg by vein or mouth three times a day from Day -1.

Carfilzomib/SAHA + Gem/Bu/Mel + Auto Stem Cell Transplant SCT

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age 18 to 65 years
  • Refractory or relapsed myeloma, defined as one or more of the following: 1. Patients with myeloma treated with first-line therapy including lenalidomide, bortezomib or thalidomide, and one or more of the following: a. Less than partial response to first-line therapy. b. Relapse after 1st line therapy. 2. High-risk disease, defined by del(13q) by conventional cytogenetics, or by del(17p), t(4;14), t(14;16), t(14;20) or 1q+ by FISH. 3. Relapse after a prior autologous stem-cell transplantation (ASCT). 4. Plasma cell leukemia. 5. Plasmablastic lymphoma. 6. Soft tissue plasmacytoma.
  • Adequate renal function, as defined by serum creatinine \</=1.8 mg/dL and/or estimated serum creatinine clearance \>/=50 ml/min.
  • Adequate hepatic function, as defined by serum glutamate oxaloacetate (SGOT) and/or serum glutamic-pyruvic transaminase (SGPT) \</=3 x upper limit of normal; serum bilirubin and alkaline phosphatase \</=2 x upper limit of normal, unless proven to be due to disease involvement.
  • Adequate pulmonary function with FEV1, FVC and 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.
  • Zubrod performance status \<2.
  • Negative Beta HCG text in a woman with child-bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization.

You may not qualify if:

  • Patients with grade \>/= 3 non-hematologic toxicity from previous therapy that has not resolved to \</= grade 1.
  • Prior whole brain irradiation.
  • Active hepatitis B, either active carrier (HBsAg +) or viremic (HBV 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.
  • HIV infection, unless the patient is receiving effective antiretroviral therapy with undetectable viral load and normal CD4 counts.
  • Patients having received radiation therapy to head and neck (excluding eyes), and internal organs of chest, abdomen or pelvis in the month prior to enrollment.
  • Autologous stem-cell transplant in the previous six months.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Links

MeSH Terms

Conditions

Neoplasms, Plasma CellMultiple MyelomaRecurrence

Interventions

carfilzomibVorinostatGemcitabineBusulfanMelphalanStem Cell TransplantationFibroblast Growth Factor 7DexamethasoneCalcium DobesilateGlutamineHealth ResourcesPyridoxine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System DiseasesDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

AnilidesAmidesOrganic ChemicalsAniline CompoundsAminesHydroxamic AcidsHydroxylaminesHydroxy AcidsCarboxylic AcidsHeterocyclic CompoundsDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingButylene GlycolsGlycolsAlcoholsMesylatesAlkanesulfonatesAlkanesulfonic AcidsAlkanesHydrocarbons, AcyclicHydrocarbonsSulfonic AcidsSulfur AcidsSulfur CompoundsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedPhenylalanineAmino Acids, AromaticAmino Acids, CyclicAmino AcidsAmino Acids, Peptides, and ProteinsCell TransplantationCell- and Tissue-Based TherapyBiological TherapyTherapeuticsTransplantationSurgical Procedures, OperativeFibroblast Growth FactorsIntercellular Signaling Peptides and ProteinsPeptidesProteinsBiological FactorsPregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsSteroids, FluorinatedBenzenesulfonatesBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicArylsulfonatesArylsulfonic AcidsAmino Acids, BasicAmino Acids, DiaminoAmino Acids, NeutralHealth PlanningHealth Care Economics and OrganizationsDelivery of Health CareHealth Care Quality, Access, and EvaluationVitamin B 6PicolinesPyridines

Study Officials

  • Yago Nieto, MD,PHD

    M.D. Anderson Cancer Center

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 11, 2014

First Posted

April 15, 2014

Study Start

September 1, 2014

Primary Completion

September 1, 2018

Last Updated

July 11, 2014

Record last verified: 2014-07