Chemotherapy and Vaccine Therapy Followed by Bone Marrow or Peripheral Stem Cell Transplantation and Interleukin-2 in Treating Patients With Recurrent or Refractory Brain Cancer

NCT ID: NCT00014573

Last Updated: 2013-04-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 1998-08-31
• Study Completion Date: 2004-10-31

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow or peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. Vaccines made from a person's white blood cells and tumor cells may make the body build an immune response to kill tumor cells. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy and vaccine therapy followed by bone marrow or peripheral stem cell transplantation and interleukin-2 in treating patients who have recurrent or refractory brain cancer.

Detailed Description

OBJECTIVES:

• Determine the effectiveness of induction paclitaxel and cyclophosphamide followed by autologous tumor cell vaccine and sargramostim (GM-CSF) followed by high-dose chemotherapy with cisplatin, cyclophosphamide, and carmustine, autologous bone marrow or peripheral blood stem cell transplantation, and interleukin-2 in patients with recurrent or refractory primary high-grade brain tumors.
• Determine the safety and toxicity of this regimen in these patients.
• Determine if a specific quantitative cellular response can be elicited in patients treated with this regimen.

OUTLINE: After partial surgical resection of tumor, patients receive induction chemotherapy comprising paclitaxel IV over 3 hours and cyclophosphamide IV over 1 hour on day 1. Patients also receive filgrastim (G-CSF) subcutaneously (SC) daily beginning on day 3 and continuing until peripheral blood stem cell (PBSC) or bone marrow collection is completed.

After the collection of PBSC or bone marrow, patients receive autologous tumor cell vaccine and sargramostim (GM-CSF) SC once every 2 weeks for up to 5 vaccinations. Two weeks after the last vaccination, patients undergo a second leukapheresis to collect lymphocytes.

After completion of the second leukapheresis, patients receive high-dose chemotherapy comprising cisplatin IV continuously over 24 hours on day -5, cyclophosphamide IV over 1 hour on days -5, -4, and -3, and carmustine IV over 2 hours on day -2. Patients undergo autologous bone marrow or PBSC transplantation on day 0. Patients receive G-CSF IV daily beginning on day 0 and continuing until blood counts recover.

Approximately 12 weeks after bone marrow or PBSC transplantation, patients receive autologous lymphocytes IV over 2-5 hours. Patients also receive interleukin-2 IV once every other day for 10 days.

Patients are followed at 18, 24, 36, 40, and 52 weeks.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

aldesleukin

Intervention Type: BIOLOGICAL

autologous tumor cell vaccine

Intervention Type: BIOLOGICAL

filgrastim

Intervention Type: BIOLOGICAL

sargramostim

Intervention Type: BIOLOGICAL

therapeutic autologous lymphocytes

Intervention Type: BIOLOGICAL

carmustine

Intervention Type: DRUG

cisplatin

Intervention Type: DRUG

cyclophosphamide

Intervention Type: DRUG

paclitaxel

Intervention Type: DRUG

autologous bone marrow transplantation

Intervention Type: PROCEDURE

conventional surgery

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed active recurrent or refractory primary high-grade brain tumor

• Tumor must be surgically accessible
• Bidimensionally measurable disease by clinical exam, CT scan, or x-ray

• Disease must be outside a previously irradiated field or have progressed or developed after radiotherapy
• Previously treated metastatic bony lesions are not considered measurable
• No previously irradiated metastatic disease site unless no response or clear progression on imaging

PATIENT CHARACTERISTICS:

Age:

• 65 and under

Performance status:

• CALGB 0-2

Life expectancy:

• More than 3 months

Hematopoietic:

• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• Liver function less than 2.5 times normal unless due to disease
• No active hepatitis B or C

Renal:

• Creatinine less than 1.5 mg/dL
• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• Left ventricular ejection fraction greater than 50% by MUGA or 2-D echocardiogram
• Electrocardiogram normal

Pulmonary:

• FEV1 and DLCO greater than 50% predicted OR
• Clearance by pulmonologist

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No serious underlying co-morbid disease or other medical or psychiatric factor that would preclude study
• Able to be weaned off steroids after surgery

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Recovered from prior conventional chemotherapy

Endocrine therapy:

• No concurrent steroid therapy for mass effect

Radiotherapy:

• See Disease Characteristics
• Recovered from prior conventional radiotherapy

Surgery:

• See Disease Characteristics

• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Barbara Ann Karmanos Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Esteban Abella, MD

Role: STUDY_CHAIR

Barbara Ann Karmanos Cancer Institute

Locations

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Countries

United States

Other Identifiers

P30CA022453

Identifier Type: NIH

Identifier Source: secondary_id

View Link

WSU-D-1654

Identifier Type: -

Identifier Source: secondary_id

WSU-07-92-98-P04-FB

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-G01-1937

Identifier Type: -

Identifier Source: secondary_id

CDR0000068559

Identifier Type: -

Identifier Source: org_study_id