A Phase I Study of a Prolonged Infusion of Triapine in Combination With a Fixed Dose Rate of Gemcitabine in Patients With Advanced Solid Tumors and Lymphomas
18 Years
N/A
Both
Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Intraocular Lymphoma, Nodal Marginal Zone B-cell Lymphoma, Primary Central Nervous System Hodgkin Lymphoma, Primary Central Nervous System Non-Hodgkin Lymphoma, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Hodgkin Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Adult T-cell Leukemia/Lymphoma, Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Mycosis Fungoides/Sezary Syndrome, Recurrent Small Lymphocytic Lymphoma, Small Intestine Lymphoma, Splenic Marginal Zone Lymphoma, Stage III Adult Burkitt Lymphoma, Stage III Adult Diffuse Large Cell Lymphoma, Stage III Adult Diffuse Mixed Cell Lymphoma, Stage III Adult Diffuse Small Cleaved Cell Lymphoma, Stage III Adult Hodgkin Lymphoma, Stage III Adult Immunoblastic Large Cell Lymphoma, Stage III Adult Lymphoblastic Lymphoma, Stage III Adult T-cell Leukemia/Lymphoma, Stage III Cutaneous T-cell Non-Hodgkin Lymphoma, Stage III Grade 1 Follicular Lymphoma, Stage III Grade 2 Follicular Lymphoma, Stage III Grade 3 Follicular Lymphoma, Stage III Mantle Cell Lymphoma, Stage III Marginal Zone Lymphoma, Stage III Mycosis Fungoides/Sezary Syndrome, Stage III Small Lymphocytic Lymphoma, Stage IV Adult Burkitt Lymphoma, Stage IV Adult Diffuse Large Cell Lymphoma, Stage IV Adult Diffuse Mixed Cell Lymphoma, Stage IV Adult Diffuse Small Cleaved Cell Lymphoma, Stage IV Adult Hodgkin Lymphoma, Stage IV Adult Immunoblastic Large Cell Lymphoma, Stage IV Adult Lymphoblastic Lymphoma, Stage IV Adult T-cell Leukemia/Lymphoma, Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma, Stage IV Grade 1 Follicular Lymphoma, Stage IV Grade 2 Follicular Lymphoma, Stage IV Grade 3 Follicular Lymphoma, Stage IV Mantle Cell Lymphoma, Stage IV Marginal Zone Lymphoma, Stage IV Mycosis Fungoides/Sezary Syndrome, Stage IV Small Lymphocytic Lymphoma, Unspecified Adult Solid Tumor, Protocol Specific, Waldenström Macroglobulinemia
Trial Information
A Phase I Study of a Prolonged Infusion of Triapine in Combination With a Fixed Dose Rate of Gemcitabine in Patients With Advanced Solid Tumors and Lymphomas
PRIMARY OBJECTIVES:
I. To determine the maximal tolerable dose (MTD) of 3-AP administered as a 24 hour infusion
in combination with and fixed-dose gemcitabine hydrochloride (GEM) in patients with advanced
solid tumors or lymphomas.
SECONDARY OBJECTIVES:
I. To define the qualitative and quantitative toxicities of the 3-AP/GEM combination in
regard to organ specificity, time course, predictability, and reversibility.
II. To document the therapeutic response of this combination in those patients when
possible.
III. To measure deoxycytidine triphosphate (dCTP) levels in peripheral blood mononuclear
cells (PBMCs) before and after treatment at specified times and try to correlate findings to
activity and toxicity of 3-AP.
IV. To perform limited pharmacokinetic analysis.
OUTLINE: This is a dose-escalation study of 3-AP (Triapine®).Patients receive 3-AP
(Triapine®) IV over 24 hours followed by gemcitabine hydrochloride IV over 100-125 minutes
on days 1 and 8. Treatment repeats every 3 weeks for 12 courses in the absence of disease
progression or unacceptable toxicity.
Patients achieving complete response (CR) receive 1 additional course of therapy beyond
documented CR.Cohorts of 3-6 patients receive escalating doses of 3-AP (Triapine®) 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.After completion of study
treatment, patients are followed periodically for 2 years.
Inclusion Criteria:
- Histologically or cytologically confirmed advanced solid tumors or lymphoma
- Disease considered incurable using standard treatment
- ECOG performance status ≤ 2
- Life expectancy > 12 weeks
- WBC ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Total bilirubin normal
- AST/ALT ≤ 2.5 times upper limit of normal
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception prior to and during study treatment
- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to 3-AP (Triapine®) and/or gemcitabine hydrochloride
- No known glucose-6-phosphate dehydrogenase (G6PD) deficiency
- 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 situation that would limit compliance with
study requirements
- No pulmonary disease (e.g., dyspnea at rest, supplemental oxygen requirement, or
baseline oxygen saturation < 92%)
- Prior gemcitabine hydrochloride allowed if given as a standard 30-minute infusion
- At least 4 weeks since prior gemcitabine hydrochloride
- Patient may have received < 2 lines of chemotherapy in the metastatic setting
- No prior 3-AP (Triapine®) or fixed-dose gemcitabine hydrochloride
- At least 6 weeks since prior nitrosoureas or mitomycin C
- More than 3 weeks since prior radiotherapy
- No other concurrent investigational agents
- No concurrent combination antiretroviral therapy in HIV-positive patients
- No other concurrent anticancer agents or therapies
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
MTD as assessed by the number of patients with dose-limiting toxicity (DLT)
Outcome Description:
MTD is the maximum dose level with fewer than 2 of 3/6 patients experiencing DLT. The study uses standard method phase I design of dose escalation. DLT will be defined as greater or equal to Grade 3 non-hematologic or greater or equal to Grade 4 hematologic adverse event EXCEPT: greater or equal to Grade 3 nausea and greater or equal to Grade 3 vomiting that improves with antiemetic therapy; greater or equal to Grade 3 diarrhea that improves with Lomotil; and greater or equal to Grade 4 Neutropenia that recovers to less or equal to Grade 3 within 7 days of first identification.
Outcome Time Frame:
Observed clinically for 4 hours after each 3-AP infusion during the first cycle of treatment
Safety Issue:
Yes
Principal Investigator
Tanios Bekaii-Saab
Investigator Role:
Principal Investigator
Investigator Affiliation:
Ohio State University
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2009-00119
NCT ID:
NCT00293345
Start Date:
June 2006
Completion Date:
Related Keywords:
- Anaplastic Large Cell Lymphoma
- Angioimmunoblastic T-cell Lymphoma
- Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
- Intraocular Lymphoma
- Nodal Marginal Zone B-cell Lymphoma
- Primary Central Nervous System Hodgkin Lymphoma
- Primary Central Nervous System Non-Hodgkin Lymphoma
- Recurrent Adult Burkitt Lymphoma
- Recurrent Adult Diffuse Large Cell Lymphoma
- Recurrent Adult Diffuse Mixed Cell Lymphoma
- Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
- Recurrent Adult Hodgkin Lymphoma
- Recurrent Adult Immunoblastic Large Cell Lymphoma
- Recurrent Adult Lymphoblastic Lymphoma
- Recurrent Adult T-cell Leukemia/Lymphoma
- Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
- Recurrent Grade 1 Follicular Lymphoma
- Recurrent Grade 2 Follicular Lymphoma
- Recurrent Grade 3 Follicular Lymphoma
- Recurrent Mantle Cell Lymphoma
- Recurrent Marginal Zone Lymphoma
- Recurrent Mycosis Fungoides/Sezary Syndrome
- Recurrent Small Lymphocytic Lymphoma
- Small Intestine Lymphoma
- Splenic Marginal Zone Lymphoma
- Stage III Adult Burkitt Lymphoma
- Stage III Adult Diffuse Large Cell Lymphoma
- Stage III Adult Diffuse Mixed Cell Lymphoma
- Stage III Adult Diffuse Small Cleaved Cell Lymphoma
- Stage III Adult Hodgkin Lymphoma
- Stage III Adult Immunoblastic Large Cell Lymphoma
- Stage III Adult Lymphoblastic Lymphoma
- Stage III Adult T-cell Leukemia/Lymphoma
- Stage III Cutaneous T-cell Non-Hodgkin Lymphoma
- Stage III Grade 1 Follicular Lymphoma
- Stage III Grade 2 Follicular Lymphoma
- Stage III Grade 3 Follicular Lymphoma
- Stage III Mantle Cell Lymphoma
- Stage III Marginal Zone Lymphoma
- Stage III Mycosis Fungoides/Sezary Syndrome
- Stage III Small Lymphocytic Lymphoma
- Stage IV Adult Burkitt Lymphoma
- Stage IV Adult Diffuse Large Cell Lymphoma
- Stage IV Adult Diffuse Mixed Cell Lymphoma
- Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
- Stage IV Adult Hodgkin Lymphoma
- Stage IV Adult Immunoblastic Large Cell Lymphoma
- Stage IV Adult Lymphoblastic Lymphoma
- Stage IV Adult T-cell Leukemia/Lymphoma
- Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma
- Stage IV Grade 1 Follicular Lymphoma
- Stage IV Grade 2 Follicular Lymphoma
- Stage IV Grade 3 Follicular Lymphoma
- Stage IV Mantle Cell Lymphoma
- Stage IV Marginal Zone Lymphoma
- Stage IV Mycosis Fungoides/Sezary Syndrome
- Stage IV Small Lymphocytic Lymphoma
- Unspecified Adult Solid Tumor, Protocol Specific
- Waldenström Macroglobulinemia
- Burkitt Lymphoma
- Hodgkin Disease
- Immunoblastic Lymphadenopathy
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, T-Cell
- Leukemia-Lymphoma, Adult T-Cell
- Lymphoma
- Lymphoma, Follicular
- Lymphoma, Large B-Cell, Diffuse
- Lymphoma, Non-Hodgkin
- Waldenstrom Macroglobulinemia
- Mycoses
- Mycosis Fungoides
- Sezary Syndrome
- Lymphoma, B-Cell
- Lymphoma, Large-Cell, Immunoblastic
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Lymphoma, T-Cell
- Lymphoma, T-Cell, Cutaneous
- Lymphoma, Large-Cell, Anaplastic
- Lymphoma, B-Cell, Marginal Zone
- Neoplasms
- Lymphoma, Mantle-Cell
Name | Location |
|---|---|
| Ohio State University Medical Center | Columbus, Ohio 43210 |
