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

Phase II Trial Of High Dose Cyclophosphamide, Cisplatin And Carmustine With Stem Cell Reconstitution Followed By Specific Cellular Therapy In Patients With Recurrent Or Refractory Brain Tumors

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.

Study Overview

• Status: Completed
• Conditions: Brain and Central Nervous System Tumors
• Intervention / Treatment: Biological: aldesleukin; Drug: cyclophosphamide; Drug: cisplatin; Procedure: conventional surgery; Procedure: peripheral blood stem cell transplantation; Drug: paclitaxel; Biological: filgrastim; Procedure: autologous bone marrow transplantation; Biological: sargramostim; Drug: carmustine; Biological: therapeutic autologous lymphocytes; Biological: autologous tumor cell vaccine

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: Barbara Ann Karmanos Cancer Institute
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Esteban Abella, MD, Barbara Ann Karmanos Cancer Institute

Study record dates

Study Major Dates

• Study Start: August 1, 1998
• Primary Completion (Actual): October 1, 2004
• Study Completion (Actual): October 1, 2004

Study Registration Dates

• First Submitted: April 10, 2001
• First Submitted That Met QC Criteria: April 2, 2004
• First Posted (Estimate): April 5, 2004

Study Record Updates

• Last Update Posted (Estimate): April 8, 2013
• Last Update Submitted That Met QC Criteria: April 5, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: childhood high-grade cerebral astrocytoma; adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma; recurrent adult brain tumor; adult anaplastic astrocytoma; adult anaplastic ependymoma; adult brain stem glioma; adult central nervous system germ cell tumor; adult choroid plexus tumor; adult ependymoblastoma; adult medulloblastoma; adult grade III meningioma; adult mixed glioma; childhood infratentorial ependymoma; childhood supratentorial ependymoma; recurrent childhood supratentorial primitive neuroectodermal tumor; recurrent childhood cerebral astrocytoma; recurrent childhood ependymoma; recurrent childhood brain stem glioma; recurrent childhood medulloblastoma; childhood central nervous system germ cell tumor; childhood choroid plexus tumor; childhood grade III meningioma
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms; Neoplasms by Site; Nervous System Neoplasms; Central Nervous System Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Aldesleukin; Cyclophosphamide; Paclitaxel; Carmustine; Sargramostim
• Other Study ID Numbers: CDR0000068559; P30CA022453 (U.S. NIH Grant/Contract); WSU-D-1654; WSU-07-92-98-P04-FB (Other Identifier: Wayne State University - Human Investigation Committee); NCI-G01-1937