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Low-Dose Melphalan and Dexamethasone Compared With High-Dose Melphalan Followed By Autologous Stem Cell Transplant in Treating Patients With Primary Systemic Amyloidosis

13 aprile 2016 aggiornato da: Mayo Clinic

Phase III Trial of Stem Cell Transplantation Compared to Parenteral Melphalan and Oral Dexamethasone in the Treatment of Primary Systemic Amyloidosis (AL)

RATIONALE: Drugs used in chemotherapy, such as melphalan and dexamethasone, work in different ways to stop the growth of plasma cells, either by killing the cells or by stopping them from dividing. Having an autologous stem cell transplant to replace the blood-forming cells destroyed by chemotherapy, allows higher doses of chemotherapy to be given so that more plasma cells are killed. By reducing the number of plasma cells, the disease may progress more slowly. It is not yet known whether combination chemotherapy is more effective than chemotherapy followed by an autologous stem cell transplant in treating primary systemic amyloidosis.

PURPOSE: This randomized phase III trial is studying the side effects and how well giving low-dose melphalan together with dexamethasone works compared with high-dose melphalan followed by an autologous stem cell transplant in treating patients with primary systemic amyloidosis.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

OBJECTIVES:

Primary

  • Compare hematologic response rate in patients with primary systemic amyloidosis treated with conventional chemotherapy comprising low-dose melphalan and dexamethasone vs high-dose melphalan followed by autologous stem cell transplantation.
  • Compare the toxicity of these regimens in these patients.

Secondary

  • Compare the overall and progression-free survival of patients treated with these regimens.
  • Compare the regression of organ involvement in patients treated with these regimens.
  • Compare the duration of response in patients treated with these regimens.
  • Correlate clonal burden and time to in vitro amyloid formation with clinical outcomes in patients treated with these regimens.
  • Compare quality of life of patients treated with these regimens.
  • Compare the information-seeking behavior in patients treated with these regimens.

OUTLINE: This is a comprehensive cohort study comprising a randomized option and a nonrandomized option. Patients consenting to randomization are stratified by risk group (high vs low) and ECOG performance status (0-1 vs 2). They are then randomized to 1 of 2 treatment arms. Patients not consenting to randomization choose their treatment arm.

  • Arm I: Patients receive low-dose melphalan IV over 15-30 minutes on day 1 or orally once daily on days 1-7 and oral dexamethasone on days 1-4 and 22-25. Treatment repeats every 6 weeks for 10 courses in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive filgrastim (G-CSF) on days -7 to -3 and undergo autologous hematopoietic stem cell (HSC) collection. Patients receive high-dose melphalan IV over 1 hour on days -2 and -1 and undergo autologous HSC transplantation on day 0.

Blood and bone marrow samples are collected at baseline. Samples are examined by PCR, cDNA, and nucleotide sequence analysis to determine VH and VL gene families and carrier status. Urine is collected at baseline and analyzed for light-chain protein levels by exclusion chromatography.

Quality of life is assessed at baseline, at months 3, 9, and 12, at completion of study treatment, and then every 6 months for up to 5 years.

After completion of study treatment, patients are followed every 6 months for up to 10 years.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

89

Fase

  • Fase 3

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Stati Uniti
    • Minnesota
      • Rochester, Minnesota, Stati Uniti, 55905
        • Mayo Clinic

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

DISEASE CHARACTERISTICS:

  • Histologically confirmed primary systemic amyloidosis

    • Amyloid light-chain (AL) disease
  • Monoclonal protein by immunoelectrophoresis or immunofixation of the serum or urine OR abnormal free light-chain ratio

  • The following amyloid syndromes* are allowed:

    • Amyloid hepatomegaly
    • Cardiomyopathy
    • Proteinuria
    • Peripheral or autonomic neuropathy
    • Soft tissue involvement including the tongue, submandibular tissues, and vascular claudication
    • Diffuse interstitial pulmonary AL disease allowed if pulmonary function is adequate to allow safe transplantation NOTE: *Presence of amyloid deposits in a plasmacytoma or in bone marrow vessels in an asymptomatic patient does not constitute an amyloid syndrome
  • No secondary or familial amyloidosis
  • No multiple myeloma with lytic or destructive bone lesions or myeloma cast nephropathy
  • No multiple myeloma with > 30% plasma cells in the bone marrow
  • No amyloidosis manifested only by carpal tunnel syndrome or purpura

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Platelet count ≥ 100,000/mm³
  • Bilirubin ≤ 2.0 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 6 times ULN
  • Creatinine ≤ 3.0 mg/dL
  • No NYHA class IV heart disease
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No uncontrolled infection
  • No HIV positivity

PRIOR CONCURRENT THERAPY:

  • Prior alkylating agents, immunosuppressive drugs, or steroids allowed provided they were given for < 1 month

    • Therapeutic steroid doses of ≤ 15 mg per day (or equivalent) allowed at discretion of physician
  • No concurrent participation in another clinical trial involving a pharmacologic agent

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Non randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Comparatore attivo: Arm A

Patients receive low-dose melphalan IV over 15-30 minutes on day

1 or orally once daily on days 1-7 and oral dexamethasone on days 1-4 and 22-25. Treatment repeats every 6 weeks for 10 courses.

Study treatment beyond one year is not allowed.
Droga: desametasone
Dato oralmente
Droga: melphalan
Given IV or orally
Sperimentale: Arm B
Patients receive filgrastim (G-CSF) on days -7 to -3 and undergo autologous hematopoietic stem cell (HSC) collection. Patients receive high-dose melphalan IV over 1 hour on days -2 and -1 and undergo autologous HSC transplantation on day 0.
Droga: melphalan
Given IV or orally
Biologico: filgrastim
No administration information given
Procedura: trapianto autologo di cellule staminali emopoietiche
Dato il giorno 0

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Hematologic Response Rate
Lasso di tempo: 10 years

Response that was confirmed on 2 consecutive evaluations during treatment. A hematologic response consisted of a Complete response, Very Good Partial Response or Partial Response.

  • 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.
10 years

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
3 Year Overall Survival
Lasso di tempo: 3 years
Percentage of patients who were alive at 3 years. The 3-year survival rate was estimated using the Kaplan Meier method.
3 years
Organ Response to Treatment
Lasso di tempo: 10 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%.
10 years

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Mayo Clinic

Collaboratori

National Cancer Institute (NCI)

Investigatori

  • Cattedra di studio: Morie A. Gertz, MD, Mayo Clinic

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 ottobre 2005

Completamento primario (Effettivo)

1 luglio 2012

Completamento dello studio (Effettivo)

1 dicembre 2014

Date di iscrizione allo studio

Primo inviato

23 maggio 2007

Primo inviato che soddisfa i criteri di controllo qualità

23 maggio 2007

Primo Inserito (Stima)

24 maggio 2007

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Stima)

17 maggio 2016

Ultimo aggiornamento inviato che soddisfa i criteri QC

13 aprile 2016

Ultimo verificato

1 giugno 2015

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • CDR0000546745
  • P30CA015083 (Sovvenzione/contratto NIH degli Stati Uniti)
  • MC0482 (Altro identificatore: Mayo Clinic Cancer Center)
  • 1691-05 (Altro identificatore: Mayo Clinic IRB)
  • NCI-2009-01329 (Identificatore di registro: NCI-CTRP)

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

prodotto fabbricato ed esportato dagli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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