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CC-4047 and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma or Amyloidosis

20. marts 2018 opdateret af: Mayo Clinic

A Phase II Trial of CC-4047 Plus Dexamethasone in Patients With Relapsed of Refractory Multiple Myeloma or Amyloidosis

RATIONALE: Biological therapies, such as CC-4047, may stimulate the immune system in different ways and stop cancer cells from growing. Dexamethasone and CC-4047 may stop the growth of cancer cells by blocking blood flow to the cancer. Giving CC-4047 together with dexamethasone may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving CC-4047 together with dexamethasone works in treating patients with relapsed or refractory multiple myeloma or amyloidosis.

Studieoversigt

Status

Afsluttet

Detaljeret beskrivelse

OBJECTIVES:

  • To assess the response rate and duration of remission with low-dose CC-4047 plus dexamethasone in patients with relapsed or refractory multiple myeloma or amyloidosis.
  • To assess the toxicity of CC-4047 plus dexamethasone in this patient population.
  • To assess in an expansion cohort the response rate with an increase in CC-4047 dose among patients who fail to respond adequately to the initial starting dose following the first 2 courses of treatment.
  • To assess the response rate and duration of remission with CC-4047 plus dexamethasone in patients with lenalidomide resistant or refractory multiple myeloma.
  • To assess the response rate and duration of remission with CC-4047 plus dexamethasone in patients with previously treated light chain amyloidosis.
  • To assess the response rate and duration of remission with low- and high-dose CC-4047 plus dexamethasone in patients with lenalidomide and bortezomib refractory multiple myeloma.
  • To assess the response rate and duration of remission with high-dose CC-4047 plus dexamethasone in patients with relapsed or refractory myeloma who received ≤ 3 treatment regimens.

OUTLINE: Patients are grouped according to disease status (relapsed/refractory myeloma [closed to accrual as of 8/5/2008] vs lenalidomide resistant/refractory myeloma [closed to accrual as of 4/2/2009] vs previously treated light chain amyloidosis vs lenalidomide and bortezomib resistant/refractory myeloma {low-dose/day}[closed to accrual as of 11/20/09] vs lenalidomide and bortezomib resistant/refractory myeloma (high-dose/day) vs relapsed/refractory myeloma {high-dose/day}).

Patients receive oral CC-4047 on days 1-28 and oral dexamethasone on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 4 weeks and then at 6 months.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

378

Fase

  • Fase 2

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, 85259-5499
        • Mayo Clinic in Arizona
    • Florida
      • Jacksonville, Florida, Forenede Stater, 32224
        • 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 til 120 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

DISEASE CHARACTERISTICS:

  • Symptomatic multiple myeloma
  • Previously treated disease meeting one of the following criteria:

    • Have light-chain amyloidosis that has been treated with at least one prior regimen
    • Symptomatic (relapsed or refractory) multiple myeloma

      • Patients must have received 1-3 treatment regimens
      • Induction therapy followed by autologous stem cell transplantation and consolidation considered one regimen
  • Measurable disease, as defined by 1 of the following:

    • Serum monoclonal protein ≥ 1.0 g by protein electrophoresis
    • More than 200 mg of monoclonal protein in the urine on 24-hour electrophoresis
    • Serum immunoglobulin free light chain (FLC) > 10 mg/dL and an abnormal FLC ratio
    • Measurable soft tissue plasmacytoma, not previously irradiated
    • More than 30% plasma cells in bone marrow
  • At least 10% plasma cells as measured by bone marrow aspirate, bone marrow biopsy, or labeling index
  • No monoclonal gammopathy of undetermined significance (not applicable for patients with amyloid)
  • No smoldering myeloma (not applicable for patients with amyloid)

PATIENT CHARACTERISTICS:

  • ECOG performance status 0, 1, or 2
  • ANC ≥ 1,000/μL
  • Platelet count ≥ 75,000/μL
  • Creatinine ≤ 2.5 mg/dL
  • Not pregnant or nursing

    • Women must refrain from breastfeeding during study participation and for at least 28 days after discontinuation of study drug
  • Negative pregnancy test
  • Fertile female patients must use two reliable forms of contraception simultaneously at least 28 days before beginning, during, and at least 28 days after completion of study drug

    • The two methods of reliable contraception must include one highly effective method (i.e., intrauterine device [IUD], hormonal [birth control pills, injections, or implants], tubal ligation, or partner's vasectomy) and one additional effective (barrier) method (i.e., latex condom, diaphragm, or cervical cap)
  • Fertile male patients must use a latex condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 28 days after stopping treatment
  • Men must agree to abstain from donating semen or sperm during study participation and for 28 days after discontinuation of study drug
  • Willing to abstain from donating blood during study participation and for 28 days after discontinuation of study drug
  • No uncontrolled infection
  • No other active malignancy
  • No New York Heart Association class III or IV cardiac disease (all patients)

    • Serum troponin T > 0.10 ng/mL (amyloid patients only)
  • No known positivity for HIV or active hepatitis infection
  • No active deep vein thrombosis or pulmonary embolism that has not been therapeutically anticoagulated
  • No condition, including the presence of laboratory abnormalities, that places the patient at unacceptable risk for participating in the study or confounds the ability to interpret data from the study
  • No known hypersensitivity to thalidomide or lenalidomide including development of erythema nodosum if characterized by a desquamating rash
  • No peripheral neuropathy > grade 2

PRIOR CONCURRENT THERAPY:

  • All previous cancer therapy, including chemotherapy and investigational agents, must have been discontinued ≥ 2 weeks prior to study registration
  • No radiotherapy ≤ 14 days prior to study registration
  • No other concurrent anti-myeloma therapy
  • No concurrent radiotherapy, except for palliation of a single painful bone lesion or fracture
  • Routine concurrent bisphosphonate therapy allowed for patients with myeloma bone disease
  • Willing and able to take aspirin or alternate prophylactic anticoagulation

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: Ikke-randomiseret
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Relapsed Myeloma (<4 Prior Regimens)

Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle

Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.
2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
Andre navne:
  • CC-4047
Eksperimentel: Lenalidomide Refractory Myeloma

Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle

Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.
2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
Andre navne:
  • CC-4047
Eksperimentel: Bortezomib/Lenalidomide Refractory/Relapsed Myeloma

Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle

Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.
2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
Andre navne:
  • CC-4047
Eksperimentel: Bortezomib/Lenalidomide Relapsed/Refractory Myeloma

Pomalidomide: 4 mg orally once daily, days 1-28 of 28 day cycle

Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.
2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
Andre navne:
  • CC-4047
Eksperimentel: Relapsed Myeloma (< 4 Prior Regimens)

Pomalidomide: 4 mg orally once daily, days 1-28 of 28 day cycle

Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.
2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
Andre navne:
  • CC-4047
Eksperimentel: Relapsed/Refractory Myeloma

Pomalidomide: 4 mg orally once daily, days 1-21 of 28 day cycle

Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.
2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
Andre navne:
  • CC-4047
Eksperimentel: Relapsed Amyloidosis

Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle

Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.
2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
Andre navne:
  • CC-4047

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
The Number of Confirmed Hematologic Responses (Complete, Partial, or Very Good Partial Response)
Tidsramme: Duration of study (up to 3 years)

Response that was confirmed on 2 consecutive evaluations

  • Complete Response(CR): Complete disappearance of M-protein from serum and urine on immunofixation, normalization of Free Light Chain (FLC) ratio and <5% plasma cells in bone marrow.
  • Very Good Partial Response(VGPR): >=90% reduction in serum M-component; Urine M-Component <100mg per 24hours; <=5% plasma cells in bone marrow.
  • Partial Response(PR): >=50% reduction in serum M-component and/or Urine M-Component >=90% reduction or <200mg per 24hours; or >=50% decrease in difference between involved and uninvolved FLC levels.
Duration of study (up to 3 years)

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Progression Free Survival (PFS)
Tidsramme: Duration of study (up to 5 years)

PFS was defined as the time from registration to progression or death due to any cause. PFS was analyzed using Kaplan Meier method.

Progression was defined as any one or more of the following:

  • 25% increase in serum M-component (absolute increase >= 0.5g/dl)
  • 25% increase in urine M-component (absolute increase >= 200mg/24hour
  • 25% increase in the difference between involved and uninvolved Free Light Chain levels (absolute increase >= 10mg/dl)
  • 25% increase in bone marrow plasma cell percentage (absolute increase of >=10%)
  • Definite development of new bone lesion or soft tissue plasmacytomas
Duration of study (up to 5 years)
Duration of Response
Tidsramme: Duration of study (up to 5 years)
Duration of response was calculated from the documentation (date) of first response (CR, VGPR, or PR) until the date of progression or last follow-up in the subset of patients who responded. Kaplan Meier method was used to compute this outcome.
Duration of study (up to 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 Q. Lacy, MD, 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. november 2007

Primær færdiggørelse (Faktiske)

1. september 2012

Studieafslutning (Faktiske)

25. oktober 2017

Datoer for studieregistrering

Først indsendt

14. november 2007

Først indsendt, der opfyldte QC-kriterier

14. november 2007

Først opslået (Skøn)

15. november 2007

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

18. april 2018

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

20. marts 2018

Sidst verificeret

1. marts 2018

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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