NCT00112853

Brief Summary

This phase I trial is studying the side effects and best dose of tipifarnib and etoposide in treating older patients with newly diagnosed acute myeloid leukemia. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving tipifarnib together with etoposide may kill more cancer cells

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
100

participants targeted

Target at P75+ for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2005

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

June 2, 2005

Completed
1 day until next milestone

First Posted

Study publicly available on registry

June 3, 2005

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2009

Completed
Last Updated

January 9, 2013

Status Verified

January 1, 2013

Enrollment Period

4.2 years

First QC Date

June 2, 2005

Last Update Submit

January 8, 2013

Conditions

Adult Acute Megakaryoblastic Leukemia (M7)Adult Acute Minimally Differentiated Myeloid Leukemia (M0)Adult Acute Monoblastic Leukemia (M5a)Adult Acute Monocytic Leukemia (M5b)Adult Acute Myeloblastic Leukemia With Maturation (M2)Adult Acute Myeloblastic Leukemia Without Maturation (M1)Adult Acute Myeloid Leukemia With 11q23 (MLL) AbnormalitiesAdult Acute Myeloid Leukemia With Inv(16)(p13;q22)Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)Adult Acute Myelomonocytic Leukemia (M4)Adult Erythroleukemia (M6a)Adult Pure Erythroid Leukemia (M6b)Secondary Acute Myeloid LeukemiaUntreated Adult Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (4)

  • Number of patients who experience dose limiting toxicities (DLT), based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0

    Up to 28 days

  • Clinical response in terms of optimal dose combination for further study

    A response surface will be constructed using a flexible two dimensional polynomial.

    Up to 4 years

  • Clinical tolerance in terms of additive or synergistic non-hematologic toxicities grade 2 or greater

    A response surface will be constructed using a flexible two dimensional polynomial.

    Up to 4 years

  • Surrogates of response in terms of cell cycle progression and apoptosis, deoxyribonucleic acid (DNA) damage, and results of in vitro model studies (using pre-post assessments).

    A response surface will be constructed using a flexible two dimensional polynomial.

    Up to day 63

Study Arms (1)

Treatment (tipifarnib, etoposide)

EXPERIMENTAL

Patients receive oral tipifarnib twice daily on days 1-14 OR 1-21 and oral etoposide once daily on days 1-3 and 8-10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who achieve a CR may receive up to 5 additional courses of therapy beyond documentation of CR. Cohorts of 3-6 patients receive escalating doses of tipifarnib and etoposide until the 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. Up to 14 additional patients receive treatment at the MTD.

Drug: tipifarnibDrug: etoposide

Interventions

tipifarnibDRUG

Given orally

Also known as: R115777, Zarnestra
Treatment (tipifarnib, etoposide)
etoposideDRUG

Given orally

Also known as: EPEG, VP-16, VP-16-213
Treatment (tipifarnib, etoposide)

Eligibility Criteria

Age70 Years+
Sexall
Healthy VolunteersNo
Age GroupsOlder Adult (65+)

You may qualify if:

  • Adults age with established, pathologically confirmed diagnoses of newly diagnosed AML, including de novo and secondary AMLs but excluding newly diagnosed acute progranulocytic leukemia (APL, M3), will be considered eligible for study
  • ECOG performance status 0-2
  • Patient must be able to give informed consent
  • Serum creatinine =\< 2.0 mg/dl
  • SGOT and SGPT =\< 5 x upper limit normal (ULN)
  • Bilirubin =\< 2 mg/dl
  • Disease-specific criteria:
  • Newly diagnosed AML, subtypes M0,1,2,4-7 but excluding M3 (APL), including myelodysplasia (MDS)-related AML (MDS/AML) and treatment-related AML
  • Patients who have received hydroxyurea alone or have received non-cytotoxic therapies previously for MDS (e.g., thalidomide, interferon, cytokines, 5-azacytidine) will be eligible for this trial

You may not qualify if:

  • Any previous treatment with R115777 or VP-16
  • Patients receiving concomitant chemotherapy, radiation therapy or immunotherapy
  • Hyperleukocytosis with \>= 30,000 blasts/uL or rapidly rising blast count with projected doubling time of =\< 2 days
  • Acute progranulocytic leukemia (APL,M3)
  • Active CNS leukemia
  • Active, uncontrolled infection; patients with infection under active treatment and controlled with antibiotics are eligible
  • Presence of other life-threatening illness
  • Patients with mental deficits and/or psychiatric history that preclude them from giving informed consent or from following protocol
  • Patients on enzyme-inducing anti-convulsants (e.g., phenytoin, fosphenytoin, phenobarbital, primidone, carbamazepine, oxcarbazepine); patients may be changed to non-enzyme inducing anti-convulsants and stabilized before starting study treatment

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21287-8936, United States

Location

Related Publications (1)

  • Karp JE, Flatten K, Feldman EJ, Greer JM, Loegering DA, Ricklis RM, Morris LE, Ritchie E, Smith BD, Ironside V, Talbott T, Roboz G, Le SB, Meng XW, Schneider PA, Dai NT, Adjei AA, Gore SD, Levis MJ, Wright JJ, Garrett-Mayer E, Kaufmann SH. Active oral regimen for elderly adults with newly diagnosed acute myelogenous leukemia: a preclinical and phase 1 trial of the farnesyltransferase inhibitor tipifarnib (R115777, Zarnestra) combined with etoposide. Blood. 2009 May 14;113(20):4841-52. doi: 10.1182/blood-2008-08-172726. Epub 2008 Dec 24.

    PMID: 19109557DERIVED

MeSH Terms

Conditions

Leukemia, Megakaryoblastic, AcuteLeukemia, Monocytic, AcuteLeukemia, Myeloid, AcuteCongenital AbnormalitiesLeukemia, Myelomonocytic, AcuteLeukemia, Erythroblastic, Acute

Interventions

tipifarnibEtoposide

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesMyeloproliferative DisordersBone Marrow Diseases

Intervention Hierarchy (Ancestors)

PodophyllotoxinTetrahydronaphthalenesNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic CompoundsGlucosidesGlycosidesCarbohydrates

Study Officials

  • Judith Karp

    Johns Hopkins University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 2, 2005

First Posted

June 3, 2005

Study Start

March 1, 2005

Primary Completion

May 1, 2009

Last Updated

January 9, 2013

Record last verified: 2013-01

Locations

US(1)