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A Phase I Dose-Escalation Study of R115777 (Tipifarnib) Plus PS-341 (Bortezomib) in Relapsed or Refractory Acute Leukemias


Phase 1
18 Years
N/A
Not Enrolling
Both
Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, 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) Abnormalities, Adult 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), Blastic Phase Chronic Myelogenous Leukemia, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia, Relapsing Chronic Myelogenous Leukemia, Untreated Adult Acute Lymphoblastic Leukemia, Untreated Adult Acute Myeloid Leukemia

Thank you

Trial Information

A Phase I Dose-Escalation Study of R115777 (Tipifarnib) Plus PS-341 (Bortezomib) in Relapsed or Refractory Acute Leukemias


PRIMARY OBJECTIVE:

I. Determine the dose-limiting toxicity and maximum tolerated dose of tipifarnib and
bortezomib in patients with relapsed or refractory acute myeloid leukemia, acute
lymphoblastic leukemia, or chronic myeloid leukemia in blast phase.

SECONDARY OBJECTIVES:

I. Determine the effect of this regimen on farnesyltransferase and proteasome inhibition in
peripheral blood mononuclear cells in these patients.

II. Determine the clinical efficacy of this regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11 and oral tipifarnib
twice daily on days 1-14. Treatment repeats every 21 days for 6 courses in the absence of
disease progression or unacceptable toxicity. Patients with partial response or stable
disease may continue therapy beyond 6 courses at the discretion of the investigator.

Cohorts of 3-6 patients receive escalating doses of bortezomib and tipifarnib 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.

Blood is collected periodically for protein expression studies. Bone marrow aspirates
obtained at baseline are examined by immunohistochemistry for Ki-67 activity.


Inclusion Criteria:



- Meets 1 of the following disease-specific criteria:

- Relapsed disease after =< 2 prior chemotherapy regimens (consolidation therapy
excluded)

- Primary-induction failure

- Previously untreated and deemed unfit for or refusing cytotoxic chemotherapy

- No hyperleukocytosis (leukemic blasts >= 30,000/mm^3)

- No acute promyelocytic leukemia (M3)

- No active CNS leukemia

- SGOT and SGPT =< 2 times upper limit of normal (ULN)

- Bilirubin normal

- Creatinine =< 1.5 times ULN

- No uncontrolled hypertension, congestive heart failure, angina pectoris, or
ventricular dysrhythmias

- Not pregnant or nursing

- Negative pregnancy test

- No uncontrolled disseminated intravascular coagulation

- Fertile patients must use effective contraception

- Hormonal contraception must have been initiated ≥ 1 month prior to study entry

- No active graft-vs-host disease

- No active uncontrolled infection

- No intrinsic impaired organ function

- No known allergy to imidazole drugs

- No neuropathy >= grade 1

- No known hypersensitivity to bortezomib, tipifarnib, boron, or mannitol

- No physical or psychiatric conditions that would preclude study participation,
including poorly controlled psychosis

- At least 48 hours since prior hydroxyurea

- No prior tipifarnib, bortezomib, or investigational proteasomal inhibitors

- No concurrent radiotherapy, chemotherapy, or immunotherapy

- No concurrent enzyme-inducing antiepileptic medications (e.g., phenytoin,
phenobarbital, or carbamazepine)

- ECOG performance status 0-2

- LVEF >= 40%

- Pathologically confirmed diagnosis of 1 of the following:

- Acute myeloid leukemia

- Acute lymphoblastic leukemia

- Chronic myelogenous leukemia in blast phase

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Dose-limiting toxicity and maximum tolerated dose of tipifarnib and bortezomib

Outcome Time Frame:

21 days

Safety Issue:

Yes

Principal Investigator

Jeffrey Lancet

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00147

NCT ID:

NCT00383474

Start Date:

August 2006

Completion Date:

Related Keywords:

  • Adult Acute Basophilic Leukemia
  • Adult Acute Eosinophilic Leukemia
  • 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) Abnormalities
  • Adult 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)
  • Blastic Phase Chronic Myelogenous Leukemia
  • Recurrent Adult Acute Lymphoblastic Leukemia
  • Recurrent Adult Acute Myeloid Leukemia
  • Relapsing Chronic Myelogenous Leukemia
  • Untreated Adult Acute Lymphoblastic Leukemia
  • Untreated Adult Acute Myeloid Leukemia
  • Congenital Abnormalities
  • Blast Crisis
  • Leukemia
  • Leukemia, Basophilic, Acute
  • Leukemia, Eosinophilic, Acute
  • Leukemia, Erythroblastic, Acute
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Megakaryoblastic, Acute
  • Leukemia, Monocytic, Acute
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Leukemia, Myelomonocytic, Acute
  • Leukemia, Myelomonocytic, Chronic
  • Hypereosinophilic Syndrome

Name

Location
H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida  33612