Neoplasms

All Conditions

Symptoms and General Pathology

Nervous System Diseases

Rare Diseases

Glioblastoma

Glioma

Disease Progression

Central Nervous System Neoplasms

Nervous System Neoplasms

Astrocytoma

Oligodendroglioma

Gliosarcoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

Antineoplastic Agents, Alkylating

Alkylating Agents

CLORETAZINE will be administered intravenously on day 7. The starting dose of CLORETAZINE will be 100 mg/m2 given within 3 hours after the last dose of Temodar on day 7. CLORETAZINE will be given as an IV infusion over 15-30 minutes via a freely flowing peripheral or central intravenous line. CLORETAZINE will be escalated by 50 mg/m2 for the second cohort then by 25 mg/m2 increments in the following cohorts of 3-6 patients using a standard phase I trial design until a MTD is determined. If dose level 2 has two DLTs then patients will be accrued to a new dose level of 125 mg/m2. Prior to receiving Cloretazine, blood will be drawn for gene methylation studies.

CLORETAZINE

Temozolomide will be given orally at a dose of 75mg/m2 daily on day 1 through 7. There will be no dose modification for this agent. Prior to receiving Temozolomide, blood will be drawn for gene methylation studies.

temozolomide

Jeffrey Raizer, MD

RATIONALE: Drugs used in chemotherapy, such as temozolomide and VNP40101M, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Temozolomide may also stop the growth of tumor cells by blocking blood flow to the tumor.

PURPOSE: This phase I/II trial is studying the side effects and best dose of VNP40101M when given together with temozolomide and to see how well it works in treating patients with progressive or relapsed malignant glioma.

OBJECTIVES:

* To determine the maximum tolerated dose (MTD) of VNP40101M when administered with temozolomide in patients with progressive or relapsed (first relapse) malignant glioma. (Phase I)
* To record the toxicities of VNP40101M when administered with temozolomide. (Phase I and II)
* To measure the level of AGT expression in peripheral blood monocytes before treatment with temozolomide and just prior to the administration of VNP40101M. (Phase I and II)
* To determine MGMT methylation status as well as other methylation patterns in blood and tissue from patients treated with this regimen and correlate with outcome. (Phase I and II)
* To determine the 6- and 12-month progression-free survival rates of patients treated with this regimen. (Phase II)
* To determine overall survival of patients treated with this regimen. (Phase II)
* To determine the complete and partial response rates in patients treated with this regimen. (Phase II)
* To determine CSF penetration of VNP40101M once the MTD is reached from phase I and correlate with serum/plasma pharmacokinetics. (Phase II)

OUTLINE:

* Phase I: Patients receive oral temozolomide on days 1-7 and VNP40101M IV over 15-30 minutes 2 hours after the last dose of temozolomide on day 7. Treatment repeats every 7 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of VNP40101M 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.

* Phase II: Patients receive oral temozolomide and VNP40101M as in phase I. VNP40101M is given at the MTD determined in phase I.

In both phases, patients complete the Functional Assessment of Cancer Therapy-Brain (FACT-BR) questionnaire on day 1 of each course.

Blood is collected for in vitro isolation of mononuclear cells for analysis of O\^6 alkylguanine DNA alkyltransferase on days 1 and 7 of course 1. Blood, plasma, CSF, and formalin-fixed paraffin-embedded tissue blocks are collected for gene methylation studies, including MGMT, at baseline and on day 1 of each course.

VNP40101M and Temozolomide in Treating Patients With Progressive or Relapsed Malignant Glioma

A Phase I/II Trial of Cloretazine® (VNP40101M) and Temodar® (Temozolomide) for Patients With Malignant Glioma in First Relapse or Progression

To determine the MTD of CLORETAZINE when administered with Temodar® in patients with malignant gliomas in first or second relapse

To determine the 6 and 12 month progression-free survival rate.

To record the toxicities of CLORETAZINE when administered with Temodar®.

(Toxicity is assessed continuously through routine medical monitoring of the patient throughout each cycle and all adverse events are recorded cumulatively on the case report forms).

To determine MGMT methylation status as well as other methylation patterns in blood correlate with outcome.

To determine the response rate to CLORETAZINE after Temodar® in patients with malignant gliomas in first or second relapse.

To record the toxicities of CLORETAZINE when administered after Temodar®

To measure the level of AGT expression in peripheral blood monocytes before treatment with Temodar® and just prior to the administration of CLORETAZINE.

To determine CSF penetration of CLORETAZINE once the MTD is reached from phase I and correlate with serum/plasma PK

Vion Pharmaceuticals

Northwestern University

Blood and Lymph Conditions

Immune System Diseases

Heart and Blood Diseases

Leukemia

Lymphoma

Multiple Myeloma

Neoplasms, Plasma Cell

Hematologic Neoplasms

Hodgkin Disease

Hematologic Diseases

Lymphosarcoma

Hodgkin Lymphoma

Fludarabine

Fludarabine phosphate

Thymoglobulin

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Cloretazine

Roy B. Jones, MD, PhD

Primary:

Define the maximal tolerated dose (MTD) of VNP40401M when given with hematopoietic cell transplantation (HCT)

Secondary:

* Describe the change in pharmacokinetic (PK) parameters with increasing doses of drug.
* Describe and estimate the frequency of \> Grade 3 non-hematologic/non-infectious toxicities at the MTD.
* Report the efficacy of the regimen.
* Evaluate the rate of engraftment for the regimen.

An autologous transplant uses the recipient's own stem cells, from the blood and bone marrow, for infusion.

VNP40101M is a chemotherapy drug designed to interfere with the growth and development of cancer cells, by binding to structures within cancer cells. This drug, given in higher doses, causes lowering of blood cells. Chemotherapy is commonly given to patients before a stem cell transplantation to help kill more cancer cells. After receiving this drug, stem cells are transfused (given gradually) to allow re-growth of the blood cells.

Before you can start treatment on this study, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. You will have blood drawn (about 3 tablespoons) for routine tests. You will have a physical exam, including measurement of your vital signs (blood pressure, heart rate, temperature, and breathing rate). You will have a bone marrow biopsy. To collect a bone marrow biopsy, an area of the hip or chest bone is numbed with anesthetic, and a small amount of marrow and bone is withdrawn through a large needle. You will have a chest x-ray and computed tomography (CT) and positron emission tomography (PET) scans, if required, to measure your tumor. You will have a lung function test and an electrocardiogram (ECG-a test to measure the electrical activity of the heart). Women who are able to have children must have a negative blood or urine pregnancy test. If you will have a blood pregnancy test it will be done with routine blood tests.

Before you receive treatment on this study, you will have apheresis done to collect some of your stem cells. Apheresis is the process of removing part of the blood (such as platelets or white blood cells) from the body in order to remove certain elements, such as stem cells. Then the rest of the blood is returned back to the body. Your stem cells will be put back in your body after you finish treatment with VNP40101M. Apheresis will be done by a major vein through a central venous catheter (CVC), usually in the chest. A CVC is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. The details of apheresis as well as the CVC will be described in separate consent forms. Your doctor will explain these procedures to you in more detail, and you will be required to sign a separate consent form for each procedure.

If you are found to be eligible to take part in this study, you will receive a dose of VNP40101M. The dose you receive will depend on when you enrolled in this study. The dose that you receive will remain the same throughout this study. Researchers will continue to enroll patients at the next highest dose level until the highest tolerable dose is found.

About 1 week after your stem cells are collected, you will be admitted to the hospital. You will stay in the hospital for about 3 weeks. You will then receive VNP40101M by a CVC over 6 hours.

Two days after you receive VNP40101M, the autologous stem cells (blood or bone marrow) will then be given to you by your CVC. You will receive G-CSF as an injection just under your skin daily, starting 1 week after your transplantation, which will help your blood cell levels return to normal.

You will then have blood drawn (about 5 tablespoons) for PK testing to measure the levels of VNP40101M in your blood. These samples will be drawn through a heparin lock, which will be in place for 24 hours after the study treatment is complete. A heparin lock is a small tube connected to a CVC in a vein in the arm for easy access. The heparin lock will be removed after these samples are received.

After you are released from the hospital, you will be required to stay in the Houston area for up to 1 month after the transplantation or until you are no longer experiencing any intolerable side effects. You will be asked to return to M. D. Anderson between 2-4 months following transplantation so that any late side effects of the study drug can be observed.

As part of standard care, you will have blood tests (about 3 tablespoons) for routine tests. Your health status will be followed-up to continue to check on the status of the disease. You will have a computed tomography scan and PET scan. You will also have a bone marrow biopsy.

If the disease gets worse or you experience any intolerable side effects, you will be taken off this study.

THIS IS AN INVESTIGATIONAL STUDY. VNP40101M is not FDA approved or commercially available. It is authorized for use in research only.

Up to 42 patients will take part in this study. All will be enrolled at M. D. Anderson.

Cloretazine (VNP40101M) With Hematopoietic Cell Transplantation for Hematologic Malignancies

Dose Escalation Trial of Cloretazine (VNP40101M) and Hematopoietic Cell Transplantation for Patients With Selected, Poor-Prognosis Hematologic Malignancies

M.D. Anderson Cancer Center

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
VNP40101M and Temozolomide in Treating Patients With Progressive or Relapsed Malignant Glioma	NCT00516282	Brain and Centr...	CLORETAZINE temozolomide	18 Years -	Northwestern University
Cloretazine (VNP40101M) With Hematopoietic Cell Transplantation for Hematologic Malignancies	NCT00521859	Hematologic Mal...	Cloretazine Fludarabine	18 Years - 65 Years	M.D. Anderson Cancer Center
Cloretazine (VNP40101M) With Hematopoietic Cell Transplantation for Hematologic Malignancies	NCT00521859	Hematologic Mal...	Cloretazine Fludarabine	18 Years - 65 Years	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for cloretazine

Every month we try and update this database with for cloretazine 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 cloretazine

Every month we try and update this database with for cloretazine 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 cloretazine 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.