Pilot Study of MGd + High-dose MTX-Based Chemoimmunotherapy + RT for Newly Dx PCNSL

NCT ID: NCT00734773

Last Updated: 2012-05-18

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: EARLY_PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-11-30

Brief Summary

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.

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.

Conditions

Brain and Central Nervous System Tumors; Lymphoma; Neurotoxicity

Study Design

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

Interventions

Rituximab

Infusion will be given at week 2, week 4, week 6 and week 8. Infusions can be administered at an initial rate of 100 mg/hr, and increased by 100 mg/hr increments at 30-minute intervals, to a maximum of 400 mg/hr as tolerated.

Intervention Type: BIOLOGICAL

Cytarabine

Administered by IV over 3 hours at a dose of 3 g/m2/day for 2 days given at week 17 and week 21.

Intervention Type: DRUG

Methotrexate

Administered by IV at dose of 3.5 grams/m2 on day 1 of week 1, week 3, week 5, week 7 and week 9; if CSF was positive it will also be given intrathecally on day 8 of week 1, week 3, week 5, week 7 and week 9.

Intervention Type: DRUG

Motexafin gadolinium

• Administered to the first five patients enrolled on trial, MGd will be given at 5 mg/kg q day x2 doses (completed on 2 consecutive days 1 to 2 weeks prior to day of cycle 1) to be followed by a non-infused MRI (without contrast) 1-5 hours after 2nd MGd dose (to evaluate for MGd tumor selective uptake).
• For induction chemotherapy, MGd 10 mg/kg will be given intravenously on day 8 of each cycle. MGd will be given immediately after Rituxan.
• During radiation therapy, MGd will be administered at 5 mg/kg 2-5 hours prior to WBRT, daily for the first 10 days (fractions) and then every other day of radiation thereafter.

Intervention Type: DRUG

Procarbazine hydrochloride

Taken orally, 100 mg/m2 days 1-7 of the 1st, 3rd, and 5th cycles of induction therapy.

Intervention Type: DRUG

Vincristine sulfate

Administered by IV at a dose of 1.4mg per meter squared on weeks 1, 3, 5, 7 and 9.

Intervention Type: DRUG

Radiation therapy

Given at weeks 11 through 16.

Intervention Type: RADIATION

Other Intervention Names

Rituxan; Cytosar-U; Ara-c; MTX; Rheumatrex; Trexall; MGd; Matulane; Vincasar PFS; Whole Brain Radiation Therapy (WBRT)

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pharmacyclics LLC.

INDUSTRY

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Northwestern University

Principal Investigators

Andrew M. Evens, DO, MS

Role: PRINCIPAL_INVESTIGATOR

Robert H. Lurie Cancer Center

Jeffrey J. Raizer, MD

Role: PRINCIPAL_INVESTIGATOR

Robert H. Lurie Cancer Center

Other Identifiers

STU00002443

Identifier Type: OTHER

Identifier Source: secondary_id

NU 05H7

Identifier Type: -

Identifier Source: org_study_id