Clinical trial NCT00293345: 3-AP and Gemcitabine in Treating Patients With Advanced Solid Tumors or Lymphoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-02-17
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase I trial is studying the best dose of 3-AP and the side effects of giving 3-AP together with gemcitabine in treating patients with advanced solid tumors or lymphoma. Drugs used in chemotherapy, such as 3-AP and gemcitabine (GEM), work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 3-AP may help gemcitabine kill more cancer cells by making the cells more sensitive to the drug. 3-AP may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: MTD as assessed by the number of patients with dose-limiting toxicity (DLT)
timeFrame: Observed clinically for 4 hours after each 3-AP infusion during the first cycle of treatment
Secondary outcomes:
measure: Toxicity as assessed using the NCI Common Toxicity Criteria, Version 3.0
timeFrame: Observed clinically for 4 hours after each 3-AP infusion during the first cycle of treatment and monitored until disease progression or for a maximum of 24 months following termination of treatment
measure: Therapeutic response
timeFrame: Tumor and radiologic measurements every 8 weeks from start of treatment. In addition to a baseline scan, confirmatory scans will also be obtained 8 weeks following initial documentation of an objective response.
measure: Duration of overall response
timeFrame: Baseline until disease progression or for a maximum of 24 months following termination of treatment.
measure: Duration of stable disease
timeFrame: Baseline until disease progression or for a maximum of 24 months following termination of treatment.
measure: Levels of dCTP in PBMCs correlated to activity and toxicity of 3-AP
timeFrame: PMBCs isolated immediately before and after 3-AP infusion (day 1), but before GEM is started on (day 2) on both course 1 and course 2 of treatment
measure: Pharmacokinetics as assessed by steady state concentration (Css) of 3-AP in serum
timeFrame: On the first day of infusion (course 1 only) during the last 4 hours of 3-AP infusion
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
Study officials:
affiliation: Ohio State University
name: Tanios Bekaii-Saab
role: PRINCIPAL_INVESTIGATOR
References: