- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT00564889
Lenalidomide, Cyclophosphamide, and Dexamethasone in Treating Patients With Primary Systemic Amyloidosis
A Phase II Trial of Lenalidomide (Revlimid®), Cyclophosphamide and Dexamethasone in Patients With Primary Systemic Amyloidosis
RATIONALE: Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop plasma cells from growing. Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of plasma cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with cyclophosphamide and dexamethasone may be an effective treatment for primary systemic amyloidosis.
PURPOSE: This phase II trial is studying how well giving lenalidomide together with cyclophosphamide and dexamethasone works in treating patients with primary systemic amyloidosis.
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
OBJECTIVES:
Primary
* Assess the hematologic response rate in patients with primary systemic amyloidosis treated with lenalidomide, cyclophosphamide, and dexamethasone.
Secondary
- Determine the organ response rate in patients treated with this regimen.
- Determine the toxicity of this regimen in these patients.
- Determine the time to progression in patients treated with this regimen.
- Determine the survival of patients treated with this regimen.
OUTLINE: Patients receive oral lenalidomide on days 1-21, oral cyclophosphamide* on days 1, 8, and 15, and oral dexamethasone on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
NOTE: *Patients may receive cyclophosphamide for up to 1 year. After completion of study treatment, patients are followed every 6 months for up to 3 years.
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 2
Kontakte und Standorte
Studienorte
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Arizona
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Scottsdale, Arizona, Vereinigte Staaten, 85259-5499
- Mayo Clinic in Arizona
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Florida
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Jacksonville, Florida, Vereinigte Staaten, 32224
- Mayo Clinic in Florida
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Minnesota
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Rochester, Minnesota, Vereinigte Staaten, 55905
- Mayo Clinic
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
DISEASE CHARACTERISTICS:
- Histochemical diagnosis of AL amyloidosis based on detection of green birefringent material in Congo red-stained tissue specimens by polarizing microscopy
Measurable disease, as defined by one of the following:
- Serum monoclonal protein ≥ 1.0 g by serum electrophoresis
- Urine monoclonal protein > 200 mg by 24-hour urine electrophoresis
- Serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
Symptomatic organ involvement with amyloid to justify therapy
- May include liver involvement, cardiac involvement, renal involvement, grade 1 peripheral neuropathy, or soft tissue involvement
- Must have more than skin purpura or carpal tunnel syndrome
No amyloid-specific syndrome, such as carpal tunnel syndrome or skin purpura, as only evidence of disease
- Vascular amyloid only in a bone marrow biopsy specimen or in a plasmacytoma is not indicative of systemic amyloidosis
- No clinically overt multiple myeloma (i.e., monoclonal BMPC > 30%, bone lesions, or hypercalcemia)
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- ANC ≥ 1,000/μL
- Platelet count ≥ 75,000/μL
- Creatinine < 3.0 mg/dL
- Not pregnant
- Negative pregnancy test
- Fertile patients must use two acceptable methods of contraception for ≥ 28 days prior to, during, and for ≥ 28 days after completion of study treatment
- No nursing during and for ≥ 28 days after completion of study treatment
- No blood, semen, or sperm donation during and for ≥ 28 days after completion of study treatment
- No malignancies within the past 5 years except treated basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast
- No neuropathy ≥ grade 2, defined as motor neuropathy (symptomatic weakness interfering with function, but not interfering with activities of daily living [ADL]) or sensory neuropathy (sensory alteration or paresthesia [including tingling], interfering with function, but not interfering with ADL)
- No uncontrolled infection
- No syncope within the past 30 days
- No known hypersensitivity to thalidomide, including desquamating rash with thalidomide in the past
- No known seropositivity for HIV
- No active hepatitis A, B, or C
- No New York Heart Association class III or IV heart disease
- No venous thromboembolic event within the past 42 days
- Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation - Patients intolerant to aspirin may use low molecular weight heparin
PRIOR CONCURRENT THERAPY:
- No prior lenalidomide
- More than 2 weeks since prior and no other concurrent anticancer agents or treatments
- More than 4 weeks since prior experimental agents
- No other concurrent corticosteroids except chronic steroids (maximum dose 20 mg/day of prednisone equivalent) for disorders other than amyloidosis (e.g., adrenal insufficiency or rheumatoid arthritis)
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: N / A
- Interventionsmodell: Einzelgruppenzuweisung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
---|---|
Experimental: CRD
Lenalidomide 15mg daily (days 1-21) Cyclophosphamide 300 mg/m^2 (days 1, 8, 15) Dexamethasone 40 mg weekly |
300 mg/m^2 days 1, 8 & 15 of a 28 day cycle taken orally with food
40 mg weekly taken orally
15 mg daily days 1-21 of a 28 day cycle taken orally with food
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Number of Participants Who Achieved a Confirmed Response Defined as a Complete Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR)
Zeitfenster: Duration on study (up to 3 years)
|
Response that was confirmed on 2 consecutive evaluations during treatment. 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 <=100 mg per 24 hours. Partial Response(PR): >=50% reduction in serum M-component and/or Urine M-Component >=90% reduction or <200 mg per 24 hours; or >=50% decrease in difference between involved and uninvolved FLC levels. |
Duration on study (up to 3 years)
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Number of Patients With Organ Response
Zeitfenster: Duration of study (up to 3 years)
|
Organ response was evaluated on the basis of improvement of one or more affected organ; only one parameter was required to satisfy the criteria. Response needed to be maintained for a minimum of 3 months to be considered valid. Renal response required a 50% reduction in 24-hour urine protein excretion (at least 0.5 g/d) with stable creatinine. Cardiac response required one of >= 2-mm reduction in the interventricular septal (IVS) thickness by echocardiogram, or improvement of ejection fraction by >= 20%, or improvement by 2 NYHA classes without an increase in diuretic use. Hepatic response required either >= 50% decrease in (or normalization of) an initially elevated alkaline phosphatase level or reduction in the size of the liver by at least 2 cm by radiographic determination. Gastrointestinal tract improvement was defined as normalization of a low serum carotene level, or reduction of diarrhea to < 50% of previous movements/day, or decrease in fecal fat excretion by 50%. |
Duration of study (up to 3 years)
|
Number of Participants With Severe Adverse Events
Zeitfenster: Duration of study (up to 3 years)
|
Severe adverse events were defined as grade 3 or higher, at least possibly related to study drugs.
Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.
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Duration of study (up to 3 years)
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Progression Free Survival (PFS)
Zeitfenster: Duration of study (up to 3 years)
|
Progression free survival (PFS) was defined as the time from registration to hematologic progression or death of any cause.
Progression free and alive patients were censored at the date of last follow-up.
The median PFS with 95% CI was estimated using the Kaplan Meier method.
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Duration of study (up to 3 years)
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Overall Survival (OS)
Zeitfenster: Duration of study (up to 3 years)
|
Overall survival (OS) was defined as the time from registration to death of any cause.
Surviving patients were censored at the date of last follow-up.
The median OS with 95% CI was estimated using the Kaplan Meier method.
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Duration of study (up to 3 years)
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Mitarbeiter und Ermittler
Sponsor
Mitarbeiter
Ermittler
- Studienstuhl: Shaji K. Kumar, MD, Mayo Clinic
- Hauptermittler: Craig B. Reeder, MD, Mayo Clinic
- Hauptermittler: Vivek Roy, MD, FACP, Mayo Clinic
Publikationen und hilfreiche Links
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn
Primärer Abschluss (Tatsächlich)
Studienabschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Schätzen)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Herz-Kreislauf-Erkrankungen
- Gefäßerkrankungen
- Stoffwechselerkrankungen
- Erkrankungen des Immunsystems
- Neubildungen nach histologischem Typ
- Neubildungen
- Lymphoproliferative Erkrankungen
- Immunproliferative Erkrankungen
- Hämatologische Erkrankungen
- Hämorrhagische Störungen
- Hämostasestörungen
- Paraproteinämien
- Bluteiweißstörungen
- Proteostase-Mängel
- Multiples Myelom
- Neubildungen, Plasmazelle
- Immunglobulin-Leichtketten-Amyloidose
- Amyloidose
- Plasmazytom
- Physiologische Wirkungen von Arzneimitteln
- Molekulare Mechanismen der pharmakologischen Wirkung
- Autonome Agenten
- Agenten des peripheren Nervensystems
- Entzündungshemmende Mittel
- Antirheumatika
- Antineoplastische Mittel
- Immunsuppressive Mittel
- Immunologische Faktoren
- Antiemetika
- Magen-Darm-Mittel
- Glukokortikoide
- Hormone
- Hormone, Hormonersatzstoffe und Hormonantagonisten
- Antineoplastische Mittel, hormonell
- Antineoplastische Mittel, alkylierend
- Alkylierungsmittel
- Myeloablative Agonisten
- Angiogenese-Inhibitoren
- Angiogenese-modulierende Mittel
- Wuchsstoffe
- Wachstumshemmer
- Dexamethason
- Cyclophosphamid
- Lenalidomid
Andere Studien-ID-Nummern
- MC0685 (Andere Kennung: Mayo Clinic Cancer Center)
- P30CA015083 (US NIH Stipendium/Vertrag)
- NCI-2010-01954 (Andere Kennung: NCI CTRP)
- 06-005711 (Andere Kennung: Mayo Clinic IRB)
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .
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