Clinical trial NCT00005967: Tipifarnib in Treating Patients With Advanced Hematologic Cancer
Official title: A Dose Finding Study of R115777 (NSC 702818) in Patients With Advanced Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Myeloproliferative Disorders
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Keywords: stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
recurrent adult Hodgkin lymphoma
refractory multiple myeloma
stage III multiple myeloma
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
refractory chronic lymphocytic leukemia
chronic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
chronic myelomonocytic leukemia
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III adult Burkitt lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV adult Burkitt lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
recurrent mantle cell lymphoma
polycythemia vera
primary myelofibrosis
essential thrombocythemia
chronic eosinophilic leukemia
chronic neutrophilic leukemia
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
stage III small lymphocytic lymphoma
stage III marginal zone lymphoma
stage IV small lymphocytic lymphoma
stage IV marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Randomized phase I trial to study the effectiveness of tipifarnib in treating patients who have advanced hematologic cancer. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

Detailed description: OBJECTIVES:

I. Determine the relationship between tipifarnib dose and inhibition of farnesylation in malignant cells of patients with advanced hematologic malignancies.

II. Determine the safety profile of this drug in this patient population. III. Determine the clinical activity of this drug in these patients.

OUTLINE: This is a randomized study. Patients are randomized to 1 of 4 dose levels.

Patients receive oral tipifarnib twice daily for 21 days. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After 1 course of therapy, patients may receive subsequent therapy at the maximum tolerated dose at the investigator's discretion.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed hematologic malignancy refractory to standard therapy or for which no known effective therapy exists

  * Hodgkin's or non-Hodgkin's lymphoma

    * Known bone marrow involvement
  * Acute myeloid leukemia
  * Chronic myelogenous leukemia

    * Chronic phase

      * No significant symptoms after treatment
      * No features of accelerated phase or blastic phase
    * Accelerated phase

      * WBC difficult to control with conventional busulfan or hydroxyurea in terms of dose requirement or shortening of intervals between courses
      * Rapid doubling of WBC (less than 5 days)
      * At least 10% blasts in blood or marrow
      * At least 20% blasts plus promyelocytes in blood or marrow
      * At least 20% basophils plus eosinophils in blood
      * Anemia or thrombocytopenia unresponsive to busulfan or hydroxyurea
      * Persistent thrombocytosis
      * Additional chromosome changes
      * Increasing splenomegaly
      * Development of chloromas or myelofibrosis
    * Blastic phase

      * At least 30% blasts plus promyelocytes in blood or bone marrow
  * Acute lymphoblastic leukemia
  * Chronic lymphocytic leukemia
  * Myelodysplastic syndromes

    * Refractory anemia with excess blasts (RAEB)
    * Chronic myelomonocytic leukemia
    * RAEB in transformation
  * Multiple myeloma
  * Chronic myeloproliferative diseases including, but not limited to, myelofibrosis with myeloid metaplasia
* Measurable or evaluable disease documented by radiographic, hematologic, bone marrow, or clinical examination parameters
* Refusal of allogeneic bone marrow transplantation allowed

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* Karnofsky 60-100%

Hepatic:

* Bilirubin no greater than 1.5 mg/dL
* Albumin at least 2.5 g/dL

Renal:

* Creatinine less than 2.0 mg/dL

Other:

* No other uncontrolled medical disorder
* No active inflammatory bowel disease, ileus, or other chronic malabsorption syndromes
* Not pregnant or nursing
* Fertile patients must use effective contraception during and for 2 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* At least 4 weeks since prior immunotherapy

Chemotherapy:

* At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas)
* At least 3 days since prior hydroxyurea

Endocrine therapy:

* At least 4 weeks since prior systemic steroids for multiple myeloma

Radiotherapy:

* At least 4 weeks since prior radiotherapy

Surgery:

* No prior total gastrectomy or total ileocolectomy

Other:

* No prior tipifarnib
* No concurrent proton pump inhibitors (e.g., omeprazole)

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
Study officials:
affiliation: University of Chicago
name: Todd M. Zimmerman, MD
role: STUDY_CHAIR
References:
citation: Zimmerman TM, Harlin H, Odenike OM, Berk S, Sprague E, Karrison T, Stock W, Larson RA, Ratain MJ, Gajewski TF. Dose-ranging pharmacodynamic study of tipifarnib (R115777) in patients with relapsed and refractory hematologic malignancies. J Clin Oncol. 2004 Dec 1;22(23):4816-22. doi: 10.1200/JCO.2004.03.200.