Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

SCHEDULE A: Patients receive R(+)XK469 IV over 30 minutes on days 1, 3, and 5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of R(+)XK469 until the recommended phase II dose or MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued and treated at the recommended phase II dose (for a maximum of 20 patients treated at that dose).

SCHEDULE B: Once the recommended phase II dose is determined on schedule A, additional patients are accrued and receive escalating doses of R(+)XK469 IV over 30-60 minutes on day 1, beginning at a reduced dose. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Dose escalation continues as in Schedule A.

R(+)XK469

Susan Cohn

This phase I trial is studying the side effects and best dose of R(+)XK469 in treating patients with advanced neuroblastoma. Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die.

OBJECTIVES:

I. Determine the maximum tolerated dose, recommended phase II dose, and dose-limiting toxicity of R(+)XK469 in two different dosing schedules in patients with advanced neuroblastoma.

II. Determine the safety of this drug in these patients. III. Determine the tolerance to this drug in these patients. IV. Determine the pharmacokinetics and pharmacodynamics of this drug and its metabolites in these patients.

V. Determine, preliminarily, any antineoplastic activity of this drug in these patients.

OUTLINE: This is a dose-escalation study.

SCHEDULE A: Patients receive R(+)XK469 intravenously (IV) over 30 minutes on days 1, 3, and 5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of R(+)XK469 until the recommended phase II dose or maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued and treated at the recommended phase II dose (for a maximum of 20 patients treated at that dose).

SCHEDULE B: Once the recommended phase II dose is determined on schedule A, additional patients are accrued and receive escalating doses of R(+)XK469 IV over 30-60 minutes on day 1, beginning at a reduced dose. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Dose escalation continues as in Schedule A.

R(+)XK469 in Treating Patients With Advanced Neuroblastoma

Phase I Study Of R(+)XK469 In Patients With Advanced Neuroblastoma

Defined as the highest dose studied for which the incidence of dose-limiting toxicity (DLT) was less than 33%.

Defined as the occurrence of any of the following: 1) grade 3 or higher nonhematologic toxicity except fatigue, alopecia, nausea, vomiting, 2) grade 4 thrombocytopenia or anemia, 3) any fever accompanied by granulocyte count \< 1000/mm\^3 (grade 3 or 4 neutropenia), 4) failure to recover absolute neutrophil count 1500/μL

Generally defined as the MTD. For both schedules A and B and the pediatric dosing schedule, once the recommended phase II dose has been tentatively defined, a total of 12 evaluable patients will be studied to ensure the feasibility of this dose for phase II trials. If interindividual pharmacokinetic variability is high, additional patients will be enrolled (maximum of 20 at the phase II dose) to permit adequate pharmacological characterization of XK469 and the relationship of interindividual pharmacokinetic variability to toxicity.

Performed by high-performance liquid chromatography (HPLC). Plasma metabolic ratios between metabolite and XK469 concentrations will be used as an index of metabolic activity and phenotype for each patient. The modality of the frequency distribution of metabolic ratios will be also described.

The maximum number of samples for pharmacokinetic studies will not exceed 20. Analyzed by non compartmental method using the WinNonlin software. Parameters include the elimination rate constant, the area under the concentration vs. time curve (AUC), terminal half-life, total (nonrenal + renal) clearance, and volume of distribution at steady state. Mean, standard deviation, and coefficient of variation will be determined for each parameter.

Performed by correlating area under the curve (AUC) (and other parameters) of R(+)XK469 and metabolites with observed toxicities. Specifically, we will compare the AUC in those patients who experience grade \>= 2 toxicity to those who experience grade \< 2 toxicity using a Wilcoxon, nonparametric rank-sum test.

Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.

National Cancer Institute (NCI)

Blood and Lymph Conditions

Immune System Diseases

Diseases and Abnormalities at or Before Birth

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Leukemia, Myelomonocytic, Chronic

Leukemia, Myelomonocytic, Juvenile

Myelodysplastic Syndromes

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Neoplasm Metastasis

Congenital Abnormalities

Anemia

Hematologic Neoplasms

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Anemia, Refractory, with Excess of Blasts

Leukemia, Myelomonocytic, Acute

Anemia, Refractory

Blast Crisis

Leukemia, Monocytic, Acute

Leukemia, Erythroblastic, Acute

Leukemia, Megakaryoblastic, Acute

Leukemia, Basophilic, Acute

Leukemia, Eosinophilic, Acute

Lymphoma

Hypereosinophilic Syndrome

Hematologic Diseases

Disease Attributes

Bone Marrow Diseases

Precancerous Conditions

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Chronic Disease

Myeloproliferative Disorders

Myelodysplastic-Myeloproliferative Diseases

Cell Transformation, Neoplastic

Carcinogenesis

Neoplastic Processes

Eosinophilia

Leukocyte Disorders

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Chronic Myeloid Leukemia

Acute Graft Versus Host Disease

Myelodysplastic Syndrome With Excess Blasts

Acute Monoblastic Leukemia

Acute Myelomonocytic Leukemia

Acute Erythroid Leukemia

Di Guglielmo's Syndrome

Acute Megakaryoblastic Leukemia

Acute Myeloblastic Leukemia Without Maturation

Acute Myeloblastic Leukemia With Maturation

Lymphosarcoma

Chronic Myeloproliferative Disorders

Myelodysplastic/myeloproliferative Disease

Patients receive XK469R IV over 30-60 minutes on days 1, 3, and 5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

pharmacological study

laboratory biomarker analysis

Francis Giles

Phase I trial to study the effectiveness of XK469R in treating patients who have refractory hematologic cancer. Drugs used in chemotherapy, such XK469R, work in different ways to stop cancer cells from dividing so they stop growing or die

PRIMARY OBJECTIVES:

I. Determine the dose-limiting toxicity, maximum tolerated dose, and recommended phase II dose of XK469R in patients with refractory hematologic malignancies.

II. Determine the pharmacokinetics of this drug in these patients.

SECONDARY OBJECTIVES:

I. Determine the presence of genetic variations potentially affecting XK469R disposition in patients treated with this drug.

OUTLINE: This is an open-label, dose-escalation, multicenter study.

Patients receive XK469R IV over 30-60 minutes on days 1, 3, and 5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of XK469R until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which at least 2 of 6 patients experience dose-limiting toxicity. A total of 12 patients receive treatment at the MTD.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

XK469R in Treating Patients With Refractory Hematologic Cancer

A Phase I Study of XK469R (NSC 698215) in Patients With Refractory Hematologic Malignancies

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
R(+)XK469 in Treating Patients With Advanced Neuroblastoma	NCT00028522	Disseminated Ne... Localized Unres... Recurrent Neuro... Regional Neurob...	R(+)XK469	5 Years - 20 Years	National Cancer Institute (NCI)
XK469R in Treating Patients With Refractory Hematologic Cancer	NCT00095797	Adult Acute Bas... Adult Acute Eos... Adult Acute Meg... Adult Acute Min... Adult Acute Mon... Adult Acute Mon... Adult Acute Mye... Adult Acute Mye... Adult Acute Mye... Adult Acute Mye... Adult Acute Mye... Adult Acute Mye... Adult Acute Mye... Adult Erythrole... Adult Pure Eryt... Blastic Phase C... Chronic Myelomo... de Novo Myelody... Previously Trea... Recurrent Adult... Recurrent Adult... Refractory Anem... Refractory Anem... Refractory Chro... Relapsing Chron... Secondary Myelo... Stage III Chron... Stage IV Chroni... Untreated Adult...	R(+)XK469 pharmacological... laboratory biom...	18 Years -	National Cancer Institute (NCI)
R(+)XK469 in Treating Patients With Advanced Neuroblastoma	NCT00028522	Disseminated Ne... Localized Unres... Recurrent Neuro... Regional Neurob...	R(+)XK469	5 Years - 20 Years	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for r(+)xk469

Every month we try and update this database with for r(+)xk469 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for r(+)xk469

Every month we try and update this database with for r(+)xk469 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for r(+)xk469 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.