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Pomalidomide, Bortezomib, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma

7. april 2020 opdateret af: Mayo Clinic

MC1082: A Phase I/II Trial of Pomalidomide (CC-4047), Bortezomib, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

RATIONALE: Pomalidomide and bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bortezomib may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving pomalidomide and bortezomib together with dexamethasone may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of bortezomib when given together with pomalidomide and dexamethasone and to see how well it works in treating patients with relapsed or refractory multiple myeloma.

Studieoversigt

Detaljeret beskrivelse

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) of bortezomib in combination with pomalidomide and dexamethasone.

II. To evaluate the hematologic response rate (PR, VGPR, or CR) of pomalidomide, bortezomib and dexamethasone in patients with relapsed or refractory myeloma.

SECONDARY OBJECTIVES:

I. Time to progression.

II. To assess the toxicity of pomalidomide, bortezomib and dexamethasone in this patient population.

OUTLINE : This is a phase I, dose-escalation study of bortezomib followed by a phase II study. Patients receive oral pomalidomide on days 1-21; bortezomib IV on days 1, 8,15, 22; and oral dexamethasone on days 1, 8, 15, 22 . Treatment repeats every 28 days for 8 courses. Patients then receive maintenance therapy comprising oral pomalidomide on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

50

Fase

  • Fase 2
  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

    • Arizona
      • Scottsdale, Arizona, Forenede Stater
        • Mayo Clinic in Arizona
    • Florida
      • Jacksonville, Florida, Forenede Stater
        • Mayo Clinic in Florida
    • Minnesota
      • Rochester, Minnesota, Forenede Stater, 55905
        • Mayo Clinic

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  • Serum Creatinine =< 3 mg/dL
  • Absolute neutrophil count >= 1000/uL
  • Platelet count >= 75,000/uL
  • Measurable disease of multiple myeloma as defined by at least ONE of the following:

    • serum monoclonal protein >= 1.0 g/dL
    • > 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
    • serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
    • monoclonal bone marrow plasmacytosis >= 30% (evaluable disease)
    • measurable plasmacytoma that has not been radiated
  • ECOG Performance status (PS) 0, 1, or 2
  • Previously treated relapsed or refractory multiple myeloma
  • Patients must have received at least one prior therapy but no more than 4 therapies.

    • one or more of the prior regimens must have included lenalidomide and it has been determined the patient is refractory, resistant, or relapsed this therapy
    • prior bortezomib not required but if prior exposure, patients should not be refractory (Refractory means progression on therapy or within 60 days from the last dose of bortezomib.)
  • Provide informed written consent
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting pomalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking pomalidomide; FCBP must also agree to ongoing pregnancy testing
  • Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy
  • All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
  • Willing and able to take aspirin or alternate prophylactic anticoagulation
  • All previous cancer therapy, including chemotherapy, high dose corticosteroids, immune modulatory drugs or proteosome inhibitors must have been discontinued >= 2 weeks prior to study registration
  • Any prior treatment with investigational agents must be discontinued >= 28 days prior to study registration
  • Willing to abstain from donating blood during study participation and for 28 days after discontinuation of study drug
  • Men must agree to abstain from donating semen or sperm during study participation and for 28 days after discontinuation of study drug
  • Willingness to return to enrolling institution for follow-up

Exclusion Criteria:

  • Concomitant high dose corticosteroids (concurrent use of corticosteroids); EXCEPTION: Patients may be on chronic steroids (maximum dose 20 mg/day prednisone equivalent) if they are being given for disorders other than myeloma, i.e., adrenal insufficiency, rheumatoid arthritis, etc
  • Another malignancy undergoing active treatment with the exception of non melanoma skin cancer or in situ cervical or breast cancer
  • Pregnant women or women of reproductive ability who are unwilling to use effective contraception
  • Nursing women
  • Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 4 weeks after stopping treatment
  • Other co-morbidity which would interfere with patient's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease
  • Other concurrent chemotherapy, radiotherapy, or any ancillary therapy considered investigational: NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
  • Active DVT or PE that has not been therapeutically anticoagulated
  • Known positive for HIV or active hepatitis infection
  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
  • Known hypersensitivity to thalidomide or lenalidomide including development of erythema nodosum if characterized by a desquamating rash
  • > grade 2 peripheral neuropathy
  • Any prior use of pomalidomide

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Arm I
Patients receive oral pomalidomide on days 1-21; bortezomib IV on days 1, 8, 15, 22; and oral dexamethasone on days 1, 8, 15, 22. Treatment repeats every 28 days for 8 courses. Patients then receive maintenance therapy comprising oral pomalidomide on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Gives oralt
Andre navne:
  • Aeroseb-Dex
  • Decaderm
  • Dekadron
  • DM
  • DXM
  • Decaspray
Valgfri korrelative undersøgelser
Givet IV
Andre navne:
  • MLN341
  • PS-341
  • LDP 341
  • VELCADE
Gives oralt
Andre navne:
  • CC-4047
Optional correlative studies

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Find Maximum Tolerated Dose (MTD) of Bortezomib in Combination With Pomalidomide and Dexamethasone Out to 2.5 Years, by Count of Patients With Dose Limiting Toxicities.
Tidsramme: 2.5 years
MTD is defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients).
2.5 years
Number of Participants With a Hematologic Response (PR, VGPR, or CR)
Tidsramme: 2.5 years
The number of participants who achieve PR, VGPR, or CR as defined by The International Myeloma Working Group uniform response criteria(2011). sCR: CR as defined below plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or > 90% reduction in serum M-protein plus urine M-protein level < 100 mg/24 h. PR: > 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >90% or to < 200 mg/24 h. MR: NA. SD: Not meeting criteria for CR, VGPR, PR, or progressive disease. PD: Increase of > 25% from lowest response value in any one or more of the following: Serum M-component and/or (the absolute increase must be > 0.5 g/dL), Urine M-component and/or (the absolute increase must be > 200 mg/24 h)
2.5 years

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Progression Free Survival
Tidsramme: 2.5 years
The progression-free survival (PFS) time is defined as the time from registration to progression or death due to any cause. The distribution of progression-free survival will be estimated using the method of Kaplan-Meier. PD: Increase of > 25% from lowest response value in any one or more of the following: Serum M-component and/or (the absolute increase must be > 0.5 g/dL), Urine M-component and/or (the absolute increase must be > 200 mg/24 h)
2.5 years
Number of Participants With Adverse Events
Tidsramme: 2.5 years
Reported in Adverse Events section of the results
2.5 years

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Samarbejdspartnere

Efterforskere

  • Studiestol: Martha Lacy, M.D., Mayo Clinic
  • Ledende efterforsker: Joseph R. Mikhael, M.D., Mayo Clinic

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

1. september 2011

Primær færdiggørelse (Faktiske)

15. august 2017

Studieafslutning (Faktiske)

22. marts 2018

Datoer for studieregistrering

Først indsendt

29. september 2010

Først indsendt, der opfyldte QC-kriterier

29. september 2010

Først opslået (Skøn)

1. oktober 2010

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

17. april 2020

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

7. april 2020

Sidst verificeret

1. februar 2019

Mere information

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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