Clinical trial NCT00734773: Pilot Study of MGd + High-dose MTX-Based Chemoimmunotherapy + RT for Newly Dx PCNSL
Official title: A Pilot Study Incorporating Motexafin Gadolinium (MGd) Into High-dose Methotrexate (MTX)-Based Chemo-immunotherapy and Radiation for Patients With Newly Diagnosed Primary CNS Lymphoma
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: Brain and Central Nervous System Tumors
Lymphoma
Neurotoxicity
Keywords: neurotoxicity
primary central nervous system non-Hodgkin lymphoma
primary central nervous system Hodgkin lymphoma
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Pharmacyclics LLC.
First posted: 2008-08-14
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Toxicity of motexafin gadolinium (MGd) and rituximab added to high-dose methotrexate, procarbazine hydrochloride, and vincristine (MPV) chemotherapy
timeFrame: Day 1 (every 2 weeks), After 5th cycle, After 7th cycle, Pre Radiation Theray, Post Radiation Therapy, and Post ara-c.
measure: Toxicity of MGd added to whole-brain radiotherapy (WBRT)
timeFrame: Day 1 (every 2 weeks), After 5th cycle, After 7th cycle, Pre Radiation Theray, Post Radiation Therapy, and Post ara-c.
measure: Tumor-selective uptake of MGd
timeFrame: Day 1 (every 2 weeks), After 5th cycle, After 7th cycle, Pre Radiation Theray, Post Radiation Therapy, and Post ara-c.
Secondary outcomes:
measure: Overall response rate (complete remission [CR] and partial remission [CR]) to pre-radiation chemo-immunotherapy (R-MPV with MGd)
timeFrame: Every 3 months for the first year after completed treatment, every 4 months for the second year, every 6 months until the 5th year and then annually.
measure: Complete response rate to pre-radiation chemo-immunotherapy (R-MPV with MGd)
timeFrame: Every 3 months after completion of treatment, exams every 3 months for the first year then every 4 - 6 months thereafter.
measure: Overall survival at 1 year
timeFrame: Every 3 months for the first year after completed treatment, every 4 months for the second year, every 6 months until the 5th year and then annually.
measure: Event-free survival at 1 year
timeFrame: Every 3 months for the first year after completed treatment, every 4 months for the second year, every 6 months until the 5th year and then annually.
measure: Progression-free survival at 1 year
timeFrame: Every 3 months for the first year after completed treatment, every 4 months for the second year, every 6 months until the 5th year and then annually.
measure: Neurotoxicity of R-MVP + MGd based on pre- and post-treatment neuropsychologic testing
timeFrame: At baseline
Other outcomes:
Locations:
Study officials:
affiliation: Robert H. Lurie Cancer Center
name: Andrew M. Evens, DO, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Robert H. Lurie Cancer Center
name: Jeffrey J. Raizer, MD
role: PRINCIPAL_INVESTIGATOR
References: