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Brain and Central Nervous System TumorsEarly Phase 1NCT00734773

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

A Early Phase 1 study testing Rituximab, Cytarabine and Methotrexate in people with Brain and Central Nervous System Tumors and Lymphoma, run by Northwestern University.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Rituximab, Cytarabine and Methotrexate
How many people
0 participants
Where
No sites listed yet
Study dates
Nov 2008to not given
Phase
Early Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

About this study

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

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.

Read the 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.

Being tested
Rituximab, Cytarabine, Methotrexate, Motexafin gadolinium, Procarbazine hydrochloride
Keywords
neurotoxicity, primary central nervous system non-Hodgkin lymphoma, primary central nervous system Hodgkin lymphoma
Medical subject headings
Central Nervous System Neoplasms, Lymphoma, Neurotoxicity Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RituximabBiological

    Also called Rituxan

    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.

  • CytarabineDrug

    Also called Cytosar-U, Ara-c

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

  • MethotrexateDrug

    Also called MTX, Rheumatrex, Trexall

    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.

  • Motexafin gadoliniumDrug

    Also called MGd

    • 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.

  • Procarbazine hydrochlorideDrug

    Also called Matulane

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

  • Vincristine sulfateDrug

    Also called Vincasar PFS

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

  • Radiation therapyRadiation

    Also called Whole Brain Radiation Therapy (WBRT)

    Given at weeks 11 through 16.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Toxicity of motexafin gadolinium (MGd) and rituximab added to high-dose methotrexate, procarbazine hydrochloride, and vincristine (MPV) chemotherapy

    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.

    Measured: Day 1 (every 2 weeks), After 5th cycle, After 7th cycle, Pre Radiation Theray, Post Radiation Therapy, and Post ara-c.

  2. Toxicity of MGd added to whole-brain radiotherapy (WBRT)

    To evaluate the toxicity of MGd added to whole-brain radiotherapy (WBRT).

    Measured: Day 1 (every 2 weeks), After 5th cycle, After 7th cycle, Pre Radiation Theray, Post Radiation Therapy, and Post ara-c.

  3. Tumor-selective uptake of MGd

    To evaluate Tumor-selective uptake of MGd

    Measured: Day 1 (every 2 weeks), After 5th cycle, After 7th cycle, Pre Radiation Theray, Post Radiation Therapy, and Post ara-c.

Secondary outcomes (6)

  1. Overall response rate (complete remission [CR] and partial remission [CR]) to pre-radiation chemo-immunotherapy (R-MPV with MGd)

    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.

    Measured: 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.

  2. Complete response rate to pre-radiation chemo-immunotherapy (R-MPV with MGd)

    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.

    Measured: Every 3 months after completion of treatment, exams every 3 months for the first year then every 4 - 6 months thereafter.

  3. Overall survival at 1 year

    To assess overall survival rate.

    Measured: 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.

  4. Event-free survival at 1 year

    To assess event-free survival rate.

    Measured: 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.

  5. Progression-free survival at 1 year

    To assess progression-free survival rate.

    Measured: 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.

  6. Neurotoxicity of R-MVP + MGd based on pre- and post-treatment neuropsychologic testing

    MR perfusion and MR spectroscopy at baseline and serially when MRI imaging is done to assess response rates using these alternate forms of imaging.

    Measured: At baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Aug 2008 (estimated)
  2. Study startNov 2008

Why it stopped: Lack of funding

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00734773
Sponsor's protocol ID
NU 05H7
Other IDs
STU00002443
Status last verified
May 2012
First submitted
13 Aug 2008
Last updated
18 May 2012
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Rituximab, Cytarabine and Methotrexate in people with Brain and Central Nervous System Tumors and Lymphoma, run by Northwestern University.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 18 May 2012. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00734773.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2012.

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