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Alvocidib in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

1. juli 2013 opdateret af: National Cancer Institute (NCI)

A Phase I Dose-Escalation Study of Flavopiridol (NSC 649890) Administered as a 30 Minute Loading Dose Followed by a 4-Hour Infusion in Patients With B-Cell Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) Following Cytoreduction With Chemotherapy

This phase I trial is studying the side effects and best dose of flavopiridol in treating patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma. Drugs used in chemotherapy, such as alvocidib, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

PRIMARY OBJECTIVES:

I. Determine the toxicity profile, dose-limiting toxicity, and maximum tolerated dose of flavopiridol (alvocidib) as consolidation chemotherapy after cytoreduction chemotherapy in patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma.

SECONDARY OBJECTIVES:

I. Determine the pharmacokinetics and cellular pharmacodynamics of flavopiridol in these patients.

II. Determine the complete response (CR) and overall response rate (CR and partial response) of patients treated with flavopiridol.

OUTLINE: This is a dose-escalation study. Patients receive alvocidib intravenously (IV) over 30 minutes (loading dose), followed by alvocidib IV over 4 hours on days 1, 8, and 15.

Treatment repeats every 5 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A total of 12 patients are treated at the MTD (i.e., recommended phase II dose). Patients undergo blood collection at baseline and periodically during study for pharmacokinetic and cytokine studies (levels of tumor necrosis factor-alpha, interleukin [IL]-6, -11, and -16) by enzyme-linked immunosorbent assay (ELISA). Interphase cytogenetics, p53 mutational status, p53/ATM function, V_H mutational status, zeta-chain-associated protein kinase 70 (ZAP-70) overexpression, and single nucleotide polymorphisms are also examined.

After completion of study treatment, patients are followed at 2 months and then every 3 months for 5 years.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

24

Fase

  • Fase 1

Kontakter og lokationer

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

Studiesteder

  • Forenede Stater
    • Ohio
      • Columbus, Ohio, Forenede Stater, 43210
        • Ohio State University Medical Center

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:

  • Diagnosis of 1 of the following:

    • B-cell chronic lymphocytic leukemia (CLL)
    • Small lymphocytic lymphoma (SLL)

  • Must have received 1-3 prior therapies for CLL

    • Completed therapy 2-12 months ago
    • Prior therapy must have led to a partial response or greater
    • No evidence of progressive disease
  • ECOG performance status 0-2
  • Absolute neutrophil count ≥ 1,000/mm³
  • WBC ≤ 5,000/mm³
  • Platelet count ≥ 50,000/mm³
  • Cytopenia allowed
  • Creatinine < 2.0 mg/dL
  • Bilirubin ≤ 1.5 times normal (unless due to Gilbert's disease or hemolysis)
  • AST ≤ 2 times normal (unless due to hemolysis)
  • No secondary malignancy or other disease that would limit survival to < 2 years
  • No history of inflammatory bowel disease unless inactive for > 2 years
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • See Disease Characteristics
  • No other concurrent chemotherapy
  • No concurrent radiotherapy
  • No concurrent dexamethasone or other corticosteroid-based antiemetics
  • No concurrent chronic corticosteroid therapy

  • No other concurrent hormonal therapy except for the following:

    • Steroids for new adrenal failure
    • Hormones for nondisease-related conditions (e.g., insulin for diabetes)

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: Treatment (chemotherapy)
Patients receive alvocidib IV over 30 minutes (loading dose), followed by alvocidib IV over 4 hours on days 1, 8, and 15. Treatment repeats every 5 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Andet: laboratoriebiomarkøranalyse
Korrelative undersøgelser
Medicin: alvocidib
Givet IV
Andre navne:
  • FLAVO
  • flavopiridol
  • HMR 1275
  • L-868275
Andet: farmakologisk undersøgelse
Korrelative undersøgelser
Andre navne:
  • farmakologiske undersøgelser

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Toxicity profile of alvocidib administered as a 30 minute loading dose followed by a 4-hour infusion once weekly for 3 consecutive weeks every 5 weeks as consolidation therapy following cytoreduction chemotherapy
Tidsramme: Day 1, every 2 courses, at 2 months and then every 3 months for 5 years after completion of study treatment
Assessed utilizing the NCI Common Terminology Criteria for Adverse Events version 3.0.
Day 1, every 2 courses, at 2 months and then every 3 months for 5 years after completion of study treatment
Dose-limiting toxicity of alvocidib as consolidation chemotherapy after cytoreduction chemotherapy in patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma
Tidsramme: Course 1
The National Cancer Institute Common Toxicity Criteria version 3.0 will be used to characterize toxicity. If no patients experience dose-limiting toxicity, dose escalation will occur. If 1 patient has a dose limiting toxicity, 3 additional patients will be enrolled at that dose. If fewer than 2 of 6 patients experiences dose limiting toxicity, then the next highest dose level will be used for the subsequent cohort of 3 patients. If at any dose level two or more of the six patients experience a dose limiting toxicity, 3 additional patients will be treated at the previous dose level.
Course 1

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Pharmacokinetics and cellular pharmacodynamics of alvocidib administered in this schedule
Tidsramme: Baseline and day 1
Cytokine studies will be examined by standard ELISA assays to determine if increase IL-6 correlates with hypotension, hypoxemia, and tachycardia observed following treatment and to identify the source of production of this cytokine. We will examine interphase cytogenetics, p53 mutational status, p53/ATM functional assay, VH mutational status, and ZAP-70 over-expression.
Baseline and day 1
Complete response (CR) and overall response rate (CR and partial response) of alvocidib in patients with previously-treated CLL
Tidsramme: Baseline, every 2 courses, at 2 months and then every 3 months for 5 years after completion of study treatment
Criteria for response will utilize the Revised National Cancer Institute-sponsored Working Group Guidelines.
Baseline, every 2 courses, at 2 months and then every 3 months for 5 years after completion of study treatment

Samarbejdspartnere og efterforskere

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

Sponsor

National Cancer Institute (NCI)

Efterforskere

  • Ledende efterforsker: Leslie Andritsos, Ohio State University

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.

Generelle publikationer

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

1. september 2006

Primær færdiggørelse (Faktiske)

1. november 2012

Datoer for studieregistrering

Først indsendt

13. september 2006

Først indsendt, der opfyldte QC-kriterier

13. september 2006

Først opslået (Skøn)

15. september 2006

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

2. juli 2013

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

1. juli 2013

Sidst verificeret

1. juli 2013

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • NCI-2009-00161
  • U01CA076576 (U.S. NIH-bevilling/kontrakt)
  • OSU 05116
  • OSU-IRB-2006C0031
  • CDR0000501975
  • OSU-05116

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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