A Dose Finding Study of R115777 (NSC 702818) in Patients With Advanced Hematologic Malignancies
Phase 1
18 Years
N/A
18 Years
N/A
Not Enrolling
Both
Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes
Both
Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes
Trial Information
A Dose Finding Study of R115777 (NSC 702818) in Patients With Advanced Hematologic Malignancies
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.
Inclusion 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)
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Todd M. Zimmerman, MD
Investigator Role:
Study Chair
Investigator Affiliation:
University of Chicago
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-02342
NCT ID:
NCT00005967
Start Date:
August 2000
Completion Date:
Related Keywords:
- Chronic Myeloproliferative Disorders
- Leukemia
- Lymphoma
- Multiple Myeloma and Plasma Cell Neoplasm
- Myelodysplastic Syndromes
- 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
- Neoplasms
- Leukemia
- Lymphoma
- Lymphoma, Non-Hodgkin
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
- Myelodysplastic Syndromes
- Preleukemia
- Myeloproliferative Disorders
- Lymphoma, Large-Cell, Immunoblastic
Name | Location |
|---|---|
| University of Chicago Cancer Research Center | Chicago, Illinois 60637 |
