Intensive Chemotherapy and Autotransplantation for Patients With Newly Diagnosed Anaplastic Oligodendroglioma

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to see how effective treatment of high doses of chemotherapy is for your tumor. We will also be looking at the side effects and risks of this treatment. You will receive very high doses of chemotherapy. High doses of chemotherapy can destroy tumor cells, but it can also destroy normal bone marrow cells. These cells produce white blood cells (which fight infection), red blood cells (which carry oxygen) and platelets (which allow your blood to clot). With too few of these cells there is a serious risk of infection and bleeding. Therefore, before treatment begins, we will collect some of your own blood cells, called peripheral blood progenitor cells (PBPCs). These cells help create new blood cells. The PBPCs are frozen and saved while you are being treated. Then at the end of treatment, your PBPCs are thawed and given back to you. These healthy PBPCs will replace the blood cells that the high dose chemotherapy destroys and allow your bone marrow to recover and produce blood cells. In a prior study we treated 69 patients in a similar way. More than half were able to avoid or delay brain radiation. This new study will use a different high dose chemotherapy regimen.

Official Title
-----------------
A Phase II Trial of Intensive Chemotherapy and Autotransplantation for Patients With Newly Diagnosed Anaplastic Oligodendroglioma

Conditions
-----------------
CNS Cancer, CNS BRAIN

Intervention / Treatment
-----------------
* Drug: temozolomide followed by high dose busulfan and thiotepa


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pathologic evidence of an anaplastic oligodendroglioma. For this study, World Health Organization classification criteria will be used. Central pathology review must take place prior to high-dose therapy but need not occur prior to study entry and induction therapy. Pathologic evidence of an anaplastic mixed glioma (i.e. oligoastrocytoma). Again, histopathologic diagnosis will be made using World Health Organization classification criteria. To qualify as a mixed tumor there must be a minimum of 25% oligodendroglial element. Central pathology review must take place prior to high-dose therapy but need not occur in advance of enrollment or induction therapy. The diagnostic surgical procedure may have been a complete resection, partial resection, or biopsy. Karnofsky performance status > or equal to 60. Granulocyte count > or equal to 1.5 X 109/L. Platelet count > or equal to 100 X 109/L SGOT < than or equal to 2X upper limit of normal. Serum creatinine < than or equal to 1.5X upper limit of normal Bilirubin < than or equal to 1.5X upper limit of normal All patients must sign written informed consent. Exclusion Criteria: Systemic or leptomeningeal metastases (excluding contiguous leptomeninges) Prior cranial radiotherapy or systemic chemotherapy Other concurrent malignancy (with the exception of cervical carcinoma in situ or basal cell carcinoma of the skin) or serious illness if this would interfere with the prescribed treatment. Pregnant or lactating women Refusal to use effective contraception
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>temozolomide followed by high dose busulfan and thiotepa | Drug: temozolomide followed by high dose busulfan and thiotepa<br>* Temozolomide 200mg/m2 PO Days 1-5 recycled every 28 days Day minus -8 thiotepa 250 mg/m2 intravenously Day minus -7 thiotepa 250 mg/m2 intravenously Day minus -6 thiotepa 250 mg/m2 intravenously Day minus -5 busulfan 3.2 mg/kg intravenously over two hours Day minus -4 busulfan 3.2 mg/kg intravenously over two hours Day minus -3 busulfan 3.2 mg/kg intravenously over two hours Day minus -2 rest Day minus -1 rest Day 0 peripheral blood stem cell or bone marrow reinfusion<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progession Free Survival | To determine the duration of disease control of newly diagnosed pure and mixed anaplastic oligodendrogliomas treated with dose-intensive chemotherapy requiring hematopoietic stem cell support. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Evaluated for Toxicities |  | up to 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Brain, CNS, TEMOZOLOMIDE, Busulfan, Thiotepa