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

This study has been withdrawn prior to enrollment.
(Lack of funding)
Sponsor:
Collaborator:
Pharmacyclics
Information provided by:
Northwestern University
ClinicalTrials.gov Identifier:
NCT00734773
First received: August 13, 2008
Last updated: May 16, 2012
Last verified: May 2012
  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
Brain and Central Nervous System Tumors
Lymphoma
Neurotoxicity
Biological: Rituximab
Drug: Cytarabine
Drug: Methotrexate
Drug: Motexafin gadolinium
Drug: Procarbazine hydrochloride
Drug: Vincristine sulfate
Radiation: Radiation therapy
Phase 0

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Toxicity of motexafin gadolinium (MGd) and rituximab added to high-dose methotrexate, procarbazine hydrochloride, and vincristine (MPV) chemotherapy [ Time Frame: Day 1 (every 2 weeks), After 5th cycle, After 7th cycle, Pre Radiation Theray, Post Radiation Therapy, and Post ara-c. ] [ Designated as safety issue: Yes ]
    To evaluate toxicity of motexafin gadolinium (MGd) and rituximab to high-dose methotrexate, procarbazine hydrochloride, and vincristine (MPV) chemotherapy at Day 1 (every 2 weeks), After 5th cycle, After 7th cycle, Pre Radiation Theray, Post Radiation Therapy, and Post ara-c.

  • Toxicity of MGd added to whole-brain radiotherapy (WBRT) [ Time Frame: Day 1 (every 2 weeks), After 5th cycle, After 7th cycle, Pre Radiation Theray, Post Radiation Therapy, and Post ara-c. ] [ Designated as safety issue: Yes ]
    To evaluate the toxicity of MGd added to whole-brain radiotherapy (WBRT).

  • Tumor-selective uptake of MGd [ Time Frame: Day 1 (every 2 weeks), After 5th cycle, After 7th cycle, Pre Radiation Theray, Post Radiation Therapy, and Post ara-c. ] [ Designated as safety issue: No ]
    To evaluate Tumor-selective uptake of MGd


Secondary Outcome Measures:
  • Overall response rate (complete remission [CR] and partial remission [CR]) to pre-radiation chemo-immunotherapy (R-MPV with MGd) [ Time Frame: 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. ] [ Designated as safety issue: No ]
    MRI scan will be done with each neurologic evaluation. Neuropsychologic evaluation will be repeated approximately 6 months after the completion of therapy and at 6 months intervals thereafter for total of 2 years.

  • Complete response rate to pre-radiation chemo-immunotherapy (R-MPV with MGd) [ Time Frame: Every 3 months after completion of treatment, exams every 3 months for the first year then every 4 - 6 months thereafter. ] [ Designated as safety issue: No ]
    Repeat CSF or ocular exam will be done 3 months after completion of treatment in those patients who had evidence of CSF or ocular involvement at diagnosis. CSF will be sampled at each visit. Ocular exams will occur every 3 months for the 1st year then every 4-6 months. Further exams will only be done as needed to rule out recurrent lymphoma.

  • Overall survival at 1 year [ Time Frame: 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. ] [ Designated as safety issue: No ]
    To assess overall survival rate.

  • Event-free survival at 1 year [ Time Frame: 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. ] [ Designated as safety issue: No ]
    To assess event-free survival rate.

  • Progression-free survival at 1 year [ Time Frame: 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. ] [ Designated as safety issue: No ]
    To assess progression-free survival rate.

  • Neurotoxicity of R-MVP + MGd based on pre- and post-treatment neuropsychologic testing [ Time Frame: At baseline ] [ Designated as safety issue: Yes ]
    MR perfusion and MR spectroscopy at baseline and serially when MRI imaging is done to assess response rates using these alternate forms of imaging.


Enrollment: 0
Study Start Date: November 2008
Intervention Details:
    Biological: 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.
    Other Name: Rituxan
    Drug: 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.
    Other Names:
    • Cytosar-U
    • Ara-c
    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.
    Other Names:
    • MTX
    • Rheumatrex
    • Trexall
    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.
    Other Name: MGd
    Drug: Procarbazine hydrochloride
    Taken orally, 100 mg/m2 days 1-7 of the 1st, 3rd, and 5th cycles of induction therapy.
    Other Name: Matulane
    Drug: Vincristine sulfate
    Administered by IV at a dose of 1.4mg per meter squared on weeks 1, 3, 5, 7 and 9.
    Other Name: Vincasar PFS
    Radiation: Radiation therapy
    Given at weeks 11 through 16.
    Other Name: Whole Brain Radiation Therapy (WBRT)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Sponsors and Collaborators
Northwestern University
Pharmacyclics
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

No publications provided

Responsible Party: Andrew M. Evens, Northwestern University
ClinicalTrials.gov Identifier: NCT00734773     History of Changes
Other Study ID Numbers: NU 05H7, STU00002443
Study First Received: August 13, 2008
Last Updated: May 16, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Northwestern University:
neurotoxicity
primary central nervous system non-Hodgkin lymphoma
primary central nervous system Hodgkin lymphoma

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Lymphoma
Nervous System Neoplasms
Neurotoxicity Syndromes
Chemically-Induced Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Nervous System Diseases
Poisoning
Methotrexate
Motexafin gadolinium
Procarbazine
Vincristine
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Antimetabolites
Antimetabolites, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Contrast Media
Dermatologic Agents
Diagnostic Uses of Chemicals
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014