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Central Nervous System LymphomaPhase 1/2NCT00293475

Methotrexate, Mannitol, Rituximab, and Carboplatin in Treating Patients With Newly Diagnosed Primary Central Nervous System Lymphoma

A Phase 1/2 study testing Carboplatin, Mannitol and Methotrexate in people with Central Nervous System Lymphoma, run by OHSU Knight Cancer Institute at 4 sites in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This phase I/II trial studies the side effects of methotrexate, mannitol, rituximab, and carboplatin and to see how well they work in treating patients with primary central nervous system lymphoma. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Central Nervous System Lymphoma
What is being tested?
Carboplatin, Mannitol and Methotrexate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
81 participants
Where
4 sitesUnited States
Study dates
14 Oct 2005to 31 Jan 2023
Phase
Phase 1/2
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 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects with histopathologic confirmation of intermediate or high-grade primary central nervous system lymphoma (PCNSL) as documented by brain biopsy, or cytology (analysis from cerebral spinal fluid [CSF] or vitrectomy), and cluster of differentiation 20 (CD20) positive; whenever possible, the tumor should be characterized by immunophenotype
  • Subjects must be =< 90 days from diagnosis of PCNSL in the brain or spine; time from pathologic diagnosis to initiation of treatment should be specified; subjects with history of only ocular lymphoma are eligible if < 90 days since documented brain parenchymal disease (by imaging or by biopsy)
  • Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance score =< 3 (Karnofsky >= 30)
  • Hematocrit >= 25% (may be reached by transfusion) (performed within 14 days of registration)
  • White blood cell count >= 2.5 x 10^3/mm^3 (performed within 14 days of registration)
  • Absolute granulocyte count >= 1.2 x 10^3/mm^3 (performed within 14 days of registration)
Show all 14Show fewer
  • Platelets >= 100 x 10^3/mm^3 (or >= lower limit of institutional normal value) (performed within 14 days of registration)
  • Calculated creatinine clearance (Cr Cl) >= 50 ml/min (performed within 14 days of registration); eligible for full dose methotrexate
  • Calculated Cr Cl >= 30 ml/min (performed within 14 days of registration); eligible for reduced dose methotrexate
  • Bilirubin =< 2.0 x upper limit of institutional normal value (performed within 14 days of registration)
  • The subject may have had other systemic chemotherapy for PCNSL during the 90 days since PCNSL diagnosis; prior systemic chemotherapy must have been given at least 4 weeks prior to study entry (6 weeks for nitrosourea agents), with the exceptions of methotrexate and rituximab which may have been given at least 10 days prior; ocular lymphoma treatment may have been given any time prior to study entry; if the subject has undergone treatment for parenchymal disease and the parenchymal disease has progressed on a stable or increasing dose of steroids, the subject is not eligible for enrollment
  • Sexually active women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study treatment and for the duration of study treatment; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Subjects with a bone marrow biopsy which shows microscopic, low-level involvement of lymphoma are eligible
  • Subject with seropositivity for hepatitis B or hepatitis C must be cleared by hepatology service prior to participating in treatment protocol

Who cannot join

  • Prior cranial or spinal radiotherapy
  • Subjects with radiographic signs of excessive intra-cranial mass effect with associated rapid neurologic deterioration, and/or spinal block, are unsafe to undergo BBBD chemotherapy and are not eligible
  • Uncontrolled (over the last 30 days), clinically significant confounding medical conditions
  • Seropositivity for the human immunodeficiency virus
  • Systemic lymphoma
  • Subjects who have a positive serum human chorionic gonadotropin (hCG), are pregnant or lactating are ineligible
  • Known allergy to any of the study agents
  • Subjects who are at significant risk for general anesthesia

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Good Samaritan Hospital - Cincinnati

    Cincinnati, Ohio, 45220

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • OHSU Knight Cancer Institute

    Portland, Oregon, 97239

Other trials in United States

About this study

Official title: A Phase I/II Study of Patients With Newly Diagnosed Primary Central Nervous System Lymphoma Treated With Methotrexate/BBBD, and Adding Rituximab (an Anti CD-20 Antibody) and Carboplatin, to the Treatment Regimen

This phase I/II trial studies the side effects of methotrexate, mannitol, rituximab, and carboplatin and to see how well they work in treating patients with primary central nervous system lymphoma. Drugs used in chemotherapy, such as methotrexate and carboplatin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Osmotic blood-brain barrier disruption uses mannitol to open the blood vessels around the brain and allow cancer-killing substances to be carried directly to the brain. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Giving methotrexate, mannitol, rituximab, and carboplatin together may be an effective treatment for primary central nervous system lymphoma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the safety and toxicities of a treatment regimen consisting of rituximab (intravenously [IV]) the day prior to methotrexate (intra-arterially [IA]), and carboplatin (IA) in conjunction with blood-brain barrier disruption (BBBD) and delayed sodium thiosulfate (IV).

II. To demonstrate, adding a monoclonal antibody and carboplatin to methotrexate BBBD, that a 45% rate of complete response (CR) within the first 3 months of treatment is achieved, while excluding a CR rate as low as 30%.

SECONDARY OBJECTIVE:

  1. To estimate the response rate (counting all CRs), the two-year overall survival and the two-year event-free survival, as baselines for subsequent trials.

OUTLINE:

Patients receive rituximab IV over 5 hours on day 1, mannitol IA, methotrexate IA over 10 minutes, and carboplatin IA over 10 minutes on days 2 and 3. Patients then receive sodium thiosulfate IV over 15 minutes at 4 and 8 hours after carboplatin. Treatment repeats monthly for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 2 months, then every 2 months for 2 years, every 6 months for 1 year, and then annually for at least 2 years.

Being tested
Carboplatin, Mannitol, Methotrexate, Quality-of-Life Assessment, Rituximab

What participants receive

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

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IA

  • MannitolDrug

    Also called D-Mannitol, Mannitol, D-, Osmitrol, Resectisol

    Given IA

  • MethotrexateDrug

    Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate

    Given IA

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • RituximabBiological

    Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody

    Given IV

  • Sodium ThiosulfateDrug

    Also called Cyanide Antidote Package, Disodium Thiosulfate, S-Hydril, Sodium Hyposulfate

    Given IV

Study groups in NCT00293475
Study groupRoleWhat they receive
Treatment (rituximab, mannitol, methotrexate, carboplatin)ExperimentalPatients receive rituximab IV over 5 hours on day 1, mannitol IA, methotrexate IA over 10 minutes, and carboplatin IA over 10 minutes on days 2 and 3. Patients then receive sodium thiosulfate IV over 15 minutes at 4 and 8 hours after carboplatin. Treatment repeats monthly for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Carboplatin; Drug: Mannitol; Drug: Methotrexate; Other: Quality-of-Life Assessment; Biological: Rituximab; Drug: Sodium Thiosulfate

What is being measured

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

  1. Incidence of toxicities, assessed using National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0 (Phase I)

    Measured: Within 2 months of completion of study treatment

  2. CR rate (Phase II)

    Measured: Within the first 3 months of treatment

Secondary outcomes (2)

  1. Overall survival

    Kaplan-Meier estimates of these survival distributions will be plotted. Descriptive stratifications of these survival distributions by baseline characteristics will be evaluated using the log-rank statistic. If there are multiple predictors of these outcomes, Cox proportional hazard models will be fit to these data to determine which predictors are independent of others in a multi-variable model.

    Measured: From entry onto study until death from any cause, assessed at 2 years

  2. Event-free survival

    Kaplan-Meier estimates of these survival distributions will be plotted. Descriptive stratifications of these survival distributions by baseline characteristics will be evaluated using the log-rank statistic. If there are multiple predictors of these outcomes, Cox proportional hazard models will be fit to these data to determine which predictors are independent of others in a multi-variable model.

    Measured: From entry onto study until death or progression of disease, assessed at 2 years

Timeline

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

  1. First posted17 Feb 2006 (estimated)
  2. Study start14 Oct 2005
  3. Primary completion31 Jan 2022 (estimated)
  4. Study completion31 Jan 2023 (estimated)

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
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
81 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00293475
Sponsor's protocol ID
IRB00001012
Other IDs
NCI-2013-00787, HEM-08059-LX, CR00022596, MR00041596, MR00045915, SOL-05025-LM, SOL-05025-L, IRB00001012
Status last verified
Sep 2021
First submitted
16 Feb 2006
Last updated
22 Sep 2021
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Carboplatin, Mannitol and Methotrexate in people with Central Nervous System Lymphoma, run by OHSU Knight Cancer Institute at 4 sites in United States.

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

Who may be eligible to take part?

The sponsor lists 14 inclusion and 8 exclusion criteria. 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: status not confirmed, as of the sponsor's last update on 22 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Results are not available in the source record.

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?

Incidence of toxicities, assessed using National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0 (Phase I) (time frame: Within 2 months of completion of study treatment). The study lists 2 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 NCT00293475.

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 22 Sep 2021.

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