Motexafin Gadolinium, Combination Chemotherapy, Rituximab, and Whole-Brain Radiation Therapy in Treating Patients With Newly Diagnosed Primary Central Nervous System Lymphoma - Full Text View

Sponsors and Collaborators:	Robert H. Lurie Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00734773

Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Radiation therapy uses high-energy x-rays to kill cancer cells. Motexafin gadolinium may make cancer cells more sensitive to radiation therapy and combination chemotherapy. Giving motexafin gadolinium together with chemotherapy, rituximab, and radiation therapy may kill more cancer cells.

PURPOSE: This phase II trial is studying the side effects of giving motexafin gadolinium together with combination chemotherapy, rituximab, and whole-brain radiation therapy and to see how well it works in treating patients with newly diagnosed primary central nervous system lymphoma.

Condition	Intervention	Phase
Lymphoma Neurotoxicity	Biological: rituximab Drug: cytarabine Drug: methotrexate Drug: motexafin gadolinium Drug: procarbazine hydrochloride Drug: vincristine sulfate Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Pilot Study Incorporating Motexafin Gadolinium (MGd) Into High-Dose (MTX)-Based Chemo-Immunotherapy and Radiation for Patients With Newly Diagnosed Primary CNS Lymphoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lymphoma Radiation Therapy

Drug Information available for: Vincristine Methotrexate Cytarabine hydrochloride Motexafin gadolinium Rituximab Motexafin Cytarabine Procarbazine hydrochloride Procarbazine Vincristine sulfate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Toxicity of motexafin gadolinium (MGd) and rituximab added to high-dose methotrexate, procarbazine hydrochloride, and vincristine (MPV) chemotherapy [ Designated as safety issue: Yes ]
Toxicity of MGd added to whole-brain radiotherapy (WBRT) [ Designated as safety issue: Yes ]
Tumor-selective uptake of MGd [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall response rate (complete remission [CR] and partial remission [CR]) to pre-radiation chemo-immunotherapy (R-MPV with MGd) [ Designated as safety issue: No ]
Complete response rate to pre-radiation chemo-immunotherapy (R-MPV with MGd) [ Designated as safety issue: No ]
Overall response rate (CR and PR) to all therapy [ Designated as safety issue: No ]
Overall survival at 1 year [ Designated as safety issue: No ]
Event-free survival at 1 year [ Designated as safety issue: No ]
Progression-free survival at 1 year [ Designated as safety issue: No ]
Neurotoxicity of R-MVP + MGd based on pre- and post-treatment neuropsychologic testing [ Designated as safety issue: Yes ]

Estimated Enrollment:	5
Study Start Date:	November 2008
Estimated Primary Completion Date:	August 2011 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the safety and efficacy of motexafin gadolinium (MGd) combined with high-dose methotrexate-based chemotherapy and radiotherapy in patients with newly diagnosed primary CNS lymphoma.
Determine the toxicity of MGd and rituximab combined with high-dose methotrexate, procarbazine hydrochloride, and vincristine (MPV) in these patients.
Determine the toxicity of MGd in combination with whole-brain radiotherapy (WBRT) in these patients.
Determine the tumor-selective uptake of MGd.

Secondary

Determine the overall response rate (complete remission [CR] and partial remission [PR]) in patients treated with pre-radiotherapy and chemo-immunotherapy (R-MPV with MGd).
Determine the complete response rate in patients treated with this regimen.
Determine the overall response rate (CR and PR) in patients who complete all MGd combined with high-dose methotrexate-based chemotherapy and WBRT.
Determine the event-free and overall survival at 1 year of patients treated with this regimen.
Determine the progression-free survival at 1 year of patients treated with this regimen.
Evaluate the neurotoxicity of R-MVP with MGd based on pre- and post-treatment neuropsychologic testing.

OUTLINE:

Tumor-selective imaging: Patients receive motexafin gadolinium (MGd) IV on days 1-2 beginning 1-2 weeks prior to induction therapy. They then undergo an MRI of the brain.
Induction therapy: Patients receive methotrexate IV over 2-3 hours and vincristine IV on day 1 and rituximab IV over 5 hours and MGd IV over 30-60 minutes on day 8. Patients also receive oral procarbazine hydrochloride on days 1-7 of courses 1, 3, and 5. Treatment repeats every 14 days for 5 courses in the absence of disease progression or unacceptable toxicity. Patients with partial response receive an additional 2 courses of induction therapy.
Chemoradiotherapy: Beginning 4 weeks after completion of induction therapy, patients undergo reduced-dose whole-brain radiotherapy for 6 weeks. Patients also receive MGd IV over 30-60 minutes, beginning 2-5 hours prior to radiotherapy, for 10 days and then every other day during radiotherapy.
Consolidation therapy: After completion of chemoradiotherapy, patients receive cytarabine IV over 3 hours on days 1-2. Treatment repeats every 30 days for 2 courses. After completion of study therapy, patients are followed every 3 months for the first year, every 3-4 months for the second year, every 4-6 months until the fifth year, and then annually thereafter.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed primary CNS lymphoma (PCNSL) diagnosed by brain biopsy, CSF cytology, or vitreal biopsy
- Newly diagnosed disease
- Patients who have an inconclusive biopsy or who are not candidates for biopsy may be eligible provided they have a typical cranial MRI or CT scan (defined as the presence of hypo-, iso- or hyperdense parenchymal contrast-enhancing, usually homogeneously) mass lesion(s) and meet at least one of the following criteria:
  - Positive cerebrospinal fluid cytology for lymphoma or a monoclonal lymphocyte population as defined by cell surface markers
  - Biopsy of the vitreous or uvea demonstrating non-Hodgkin lymphoma
Measurable (defined as reproducibly measurable disease in two perpendicular dimensions on radiologic study) or evaluable disease

PATIENT CHARACTERISTICS:

ECOG performance status 0-3
Life expectancy ≥ 8 weeks
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Bilirubin ≤ 2.0 mg
SGOT ≤ 2 times upper limit of normal
Serum creatinine ≤ 1.5 mg/dL OR creatinine clearance > 50 cc/min
Not pregnant or nursing
Fertile patients must use effective contraception during and for 6 months after completion of study therapy
HIV negative
No other active primary malignancy with the exception of basal cell carcinoma of the skin or cervical carcinoma in situ

PRIOR CONCURRENT THERAPY:

No prior cranial irradiation
No prior chemotherapy for CNS lymphoma

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00734773

Locations

United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Recruiting
Chicago, Illinois, United States, 60611-3013
Contact: Clinical Trials Office - Robert H. Lurie Comprehensive Cancer 312-695-1301 cancer@northwestern.edu

Sponsors and Collaborators

Robert H. Lurie Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:	Andrew M. Evens, DO, MS	Robert H. Lurie Cancer Center
Principal Investigator:	Jeffrey J. Raizer, MD	Robert H. Lurie Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Robert H. Lurie Comprehensive Cancer Center at Northwestern University ( Andrew M. Evens )
Study ID Numbers:	CDR0000602042, NU-05H7, PCI-P-NU-05H7
Study First Received:	August 13, 2008
Last Updated:	July 7, 2009
ClinicalTrials.gov Identifier:	NCT00734773 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

neurotoxicity
primary central nervous system lymphoma

Study placed in the following topic categories:

Antimetabolites
Anti-Infective Agents
Neurotoxicity Syndromes
Immunologic Factors
Folate
Central Nervous System Lymphoma, Primary
Disorders of Environmental Origin
Vitamin B9
Methotrexate
Lymphoma
Cytarabine
Immunoproliferative Disorders
Rituximab
Poisoning
Vincristine

Antimitotic Agents
Folinic Acid
Motexafin gadolinium
Folic Acid Antagonists
Antiviral Agents
Immunosuppressive Agents
Folic Acid
Lymphatic Diseases
Photosensitizing Agents
Radiation-Sensitizing Agents
Tubulin Modulators
Procarbazine
Lymphoproliferative Disorders
Antirheumatic Agents
Antineoplastic Agents, Phytogenic

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Immunologic Factors
Neurotoxicity Syndromes
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Disorders of Environmental Origin
Reproductive Control Agents
Therapeutic Uses
Abortifacient Agents
Methotrexate
Dermatologic Agents
Lymphoma

Nucleic Acid Synthesis Inhibitors
Cytarabine
Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases
Rituximab
Mitosis Modulators
Nervous System Diseases
Poisoning
Vincristine
Enzyme Inhibitors
Antimitotic Agents
Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal
Motexafin gadolinium

ClinicalTrials.gov processed this record on September 04, 2009