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Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia

19. mars 2015 oppdatert av: National Cancer Institute (NCI)

Phase 2 Trial of R115777 in Previously Untreated Older Adults With AML and Baseline Presence of a Specific 2-Gene Expression Signature Ratio

This phase II trial is studying how well tipifarnib works in treating older patients with acute myeloid leukemia. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

PRIMARY OBJECTIVES:

I. To determine the complete remission (CR) rate in acute myeloid leukemia (AML) patients prospectively selected for tipifarnib (ZARNESTRA) treatment on the basis of a 2-gene signature (RASGRP1:APTX ratio) in bone marrow aspirates.

SECONDARY OBJECTIVES:

I. To determine the median overall and 1-year survival of patients treated with this regimen II. To determine the median relapse-free survival of patients treated with this regimen.

III. To determine the safety of this regimen in these patients IV. To determine the immunophenotypic expression of RASGRP1 on baseline bone marrow blasts and assess correlation with PCR-based detection.

OUTLINE: This is a multicenter study.

Patients receive tipifarnib orally twice daily on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Bone marrow aspirate and/or biopsy are collected at baseline and on day 28 of course 1 and 2 for RasGRP1 protein expression analysis by qRT-PCR.

After completion of study therapy, patients are followed up every 30 days.

Studietype

Intervensjonell

Registrering (Faktiske)

21

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Forente stater
    • Florida
      • Tampa, Florida, Forente stater, 33612
        • Moffitt Cancer Center
    • Georgia
      • Atlanta, Georgia, Forente stater, 30342
        • Blood and Marrow Transplant Group of Georgia
      • Atlanta, Georgia, Forente stater, 30322
        • Emory University/Winship Cancer Institute
    • Maryland
      • Baltimore, Maryland, Forente stater, 21287
        • Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
    • New York
      • New York, New York, Forente stater, 10065
        • Memorial Sloan-Kettering Cancer Center
      • New York, New York, Forente stater, 10065
        • Weill Medical College of Cornell University
    • North Carolina
      • Chapel Hill, North Carolina, Forente stater, 27599
        • University of North Carolina

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

65 år og eldre (Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  • Previously untreated acute myeloid leukemia (AML) (de novo or secondary)

    • No diagnosis of acute promyelocytic leukemia (APL)
  • Deemed unsuitable for or refuses standard induction chemotherapy
  • RASGRP1:APTX ratio >= 5, through bone marrow screening
  • No patients with known leukemic involvement of the central nervous system
  • ECOG performance status =< 2
  • No WBC >= 30,000/uL (hydroxyurea permitted up to 24 hours prior to initiation of therapy)
  • Serum creatinine less than 1.5 times the upper limit of the normal range (ULN) (National Cancer Institute [NCI] Common Toxicity Criteria [CTC] Grade 1)
  • Total bilirubin less than 1.5 times ULN (unless the increase is unequivocally due to hemolysis or Gilbert syndrome)
  • ALT and AST less than 2.5 times ULN (NCI CTC Grade 1)
  • Men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
  • No symptomatic neuropathy of grade 2 or worse
  • No uncompensated disseminated intravascular coagulation (DIC) or uncontrolled bleeding
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to tipifarnib (R115777), such as the imidazole drugs, including clotrimazole, ketoconazole, miconazole, econazole, fenticonazole, isoconazole, sulconazole, ticonazole, or terconazole
  • No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with R115777; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; known HIV-positive patients NOT on antiretroviral therapy AND with a CD4 cell count >= 400/mm^3 are eligible
  • No other concurrent cytotoxic or biologic antileukemic therapy
  • No patients who are receiving any other investigational agents

  • Use of enzyme-inducing anticonvulsants (e.g., phenytoin, fosphenytoin, phenobarbital, primidone, carbamazepine, oxcarbazepine) while taking tipifarnib (R115777) is contraindicated

    • If clinically indicated, subjects may use non-enzyme-inducing anticonvulsants during treatment with R115777

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Treatment (tipifarnib)
Patients receive tipifarnib orally twice daily on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Annen: Laboratoriebiomarkøranalyse
Korrelative studier
Legemiddel: Tipifarnib
Gitt PO
Andre navn:
  • R115777
  • Zarnestra

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Complete Remission (CR) Rate
Tidsramme: From first treatment through follow up period, an expected average of 12 months
Complete Remission (CR) rate in Acute Myelogenous Leukemia (AML) patients prospectively selected for R115777R115777 (ZARNESTRA) treatment on the basis of a 2-gene signature (RASGRP1:APTX ratio) in bone marrow aspirates. AML Complete Remission: Bone marrow aspiration - Less than 5% leukemic blasts, Auer rods not detected; Peripheral blood counts - Absolute neutrophil count >/= 1,000/mm^3, Platelet count >/= 100,000/mm^3, Leukemic blasts not present; Blood-product transfusion independence; Absence of extramedullary leukemia.
From first treatment through follow up period, an expected average of 12 months

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Median Overall Survival (OS)
Tidsramme: From first treatment through follow up period, an expected average of 12 months
Overall survival is calculated from the first day of R115777 treatment and lasts until the date of death recorded on the case report form (CRF).
From first treatment through follow up period, an expected average of 12 months
Median 1-Year Survival Rate
Tidsramme: 1 year
Prior to the early discontinuation of the study (for not meeting the primary endpoint of at least 3 CR/CRi after 2 cycles), investigators had planned to calculate one year survival from Kaplan Meier estimates.
1 year
Number of Participants With Relapse Free Survival
Tidsramme: 7 months
Relapse-free survival is calculated from the date of documentation of complete remission/morphologic complete remission with incomplete blood count recovery (CR/CRi) until disease relapse or death from any cause.
7 months

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

National Cancer Institute (NCI)

Etterforskere

  • Hovedetterforsker: Jeffrey Lancet, Moffitt Cancer Center

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. mai 2011

Primær fullføring (Faktiske)

1. november 2014

Studiet fullført (Faktiske)

1. november 2014

Datoer for studieregistrering

Først innsendt

24. mai 2011

Først innsendt som oppfylte QC-kriteriene

25. mai 2011

Først lagt ut (Anslag)

26. mai 2011

Oppdateringer av studieposter

Sist oppdatering lagt ut (Anslag)

8. april 2015

Siste oppdatering sendt inn som oppfylte QC-kriteriene

19. mars 2015

Sist bekreftet

1. februar 2015

Mer informasjon

Begreper knyttet til denne studien

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • NCI-2011-02589 (Registeridentifikator: CTRP (Clinical Trial Reporting Program))
  • U01CA070095 (U.S. NIH-stipend/kontrakt)
  • N01CM00071 (U.S. NIH-stipend/kontrakt)
  • P30CA076292 (U.S. NIH-stipend/kontrakt)
  • N01CM00100 (U.S. NIH-stipend/kontrakt)
  • 16572
  • CDR0000699713
  • 8977 (Annen identifikator: CTEP)

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