CNS BRAIN, CNS Cancer
Conditions
Keywords
Brain, CNS, TEMOZOLOMIDE, Busulfan, Thiotepa
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.
Interventions
DRUGtemozolomide followed by high dose busulfan and thiotepa
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
Sponsors
University of Calgary
Northwestern University
Northwestern Memorial Hospital
Massachusetts General Hospital
Schering-Plough
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progession Free Survival | 2 years | 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. |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants Evaluated for Toxicities | up to 2 years |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Participants With Newly Diagnosed Anaplastic Oligodendroglioma temozolomide followed by high dose busulfan and thiotepa | 60 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Not treated | 3 |
Baseline characteristics
| Characteristic | Participants With Newly Diagnosed Anaplastic Oligodendroglioma |
|---|---|
| Age, Continuous | 45 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 57 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 53 Participants |
| Region of Enrollment United States | 60 Participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 30 / 60 |
| other Total, other adverse events | 57 / 60 |
| serious Total, serious adverse events | 26 / 60 |
Outcome results
Primary
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.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With Newly Diagnosed Anaplastic Oligodendroglioma | Progession Free Survival | 85.7 % of participants without progression |
Secondary
Number of Participants Evaluated for Toxicities
Time frame: up to 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants With Newly Diagnosed Anaplastic Oligodendroglioma | Number of Participants Evaluated for Toxicities | 60 Participants |