- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT01212952
Pomalidomide, Bortezomib, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma
MC1082: A Phase I/II Trial of Pomalidomide (CC-4047), Bortezomib, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
Studieoversigt
Status
Betingelser
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
Tilmelding (Faktiske)
Fase
- Fase 2
- Fase 1
Kontakter og lokationer
Studiesteder
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Arizona
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Scottsdale, Arizona, Forenede Stater
- Mayo Clinic in Arizona
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Florida
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Jacksonville, Florida, Forenede Stater
- Mayo Clinic in Florida
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Minnesota
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Rochester, Minnesota, Forenede Stater, 55905
- Mayo Clinic
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
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
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 |
|---|---|
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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.
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Gives oralt
Andre navne:
Valgfri korrelative undersøgelser
Givet IV
Andre navne:
Gives oralt
Andre navne:
Optional correlative studies
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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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
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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).
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2.5 years
|
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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)
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2.5 years
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Progression Free Survival
Tidsramme: 2.5 years
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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)
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2.5 years
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Number of Participants With Adverse Events
Tidsramme: 2.5 years
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Reported in Adverse Events section of the results
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2.5 years
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Samarbejdspartnere og efterforskere
Sponsor
Samarbejdspartnere
Efterforskere
- Studiestol: Martha Lacy, M.D., Mayo Clinic
- Ledende efterforsker: Joseph R. Mikhael, M.D., Mayo Clinic
Publikationer og nyttige links
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Hjerte-kar-sygdomme
- Karsygdomme
- Sygdomme i immunsystemet
- Neoplasmer efter histologisk type
- Neoplasmer
- Lymfoproliferative lidelser
- Immunproliferative lidelser
- Hæmatologiske sygdomme
- Hæmoragiske lidelser
- Hæmostatiske lidelser
- Paraproteinæmier
- Blodproteinforstyrrelser
- Myelomatose
- Neoplasmer, Plasmacelle
- Lægemidlers fysiologiske virkninger
- Autonome agenter
- Agenter fra det perifere nervesystem
- Anti-inflammatoriske midler
- Antineoplastiske midler
- Immunologiske faktorer
- Antiemetika
- Gastrointestinale midler
- Glukokortikoider
- Hormoner
- Hormoner, hormonsubstitutter og hormonantagonister
- Antineoplastiske midler, hormonelle
- Angiogenese-hæmmere
- Angiogenesemodulerende midler
- Vækststoffer
- Væksthæmmere
- Dexamethason
- Pomalidomid
- Bortezomib
Andre undersøgelses-id-numre
- MC1082 (Anden identifikator: Mayo Clinic Cancer Center)
- NCI-2010-01967 (Registry Identifier: NCI's CTRO)
- 10-001545 (Anden identifikator: Mayo Clinic IRB)
- PO-MM-PI-0019 (Anden identifikator: Celgene Protocol)
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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