High-dose Sequential Chemoimmunotherapy for B-cell Lymphomas With Central Nervous System Involvement (SCNSL1)

November 22, 2024 updated by: Andrés José Maria Ferreri

High-dose Sequential Chemotherapy and Rituximab (R-HDS) in Patients With Systemic B-cell Lymphoma With Central Nervous System Involvement at Diagnosis or Relapse

This prospective trial will assess the activity and feasibility of a new high-dose methotrexate-based high-dose sequential chemotherapy combination in patients with B-cell lymphomas and CNS involvement at diagnosis or relapse. Selected drugs, with a well-documented anti-lymphoma activity, will be administered at high doses to increase blood-brain barrier penetration and CNS bioavailability as well as to reduce potential cross-resistance.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Patients with aggressive B-cell lymphoma and involvement of the central nervous system at diagnosis or relapse will be treated with a combination of high-dose methotrexate and high-dose cytarabine, rituximab, and intrathecal depocyte followed by rituximab-high-dose sequential chemotherapy supported by autologous tsem cell transplantation.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milan, Italy, 20132
        • San Raffaele Scientific Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Histologically confirmed diagnosis of diffuse large-cell, follicular or mantle cell lymphoma
  2. CNS involvement (brain, meninges, cranial nerves, eyes, and/or spinal cord) at diagnosis or relapse after conventional chemotherapy
  3. Diagnosis of CNS involvement either by brain biopsy or CSF cytology examination. Neuroimaging alone is acceptable only when stereotactic biopsy is formally contraindicated.
  4. Age 18-70 years
  5. ECOG performance status 0-3
  6. Adequate bone marrow (PLT > 100000 mm3, Hb > 9 g/dl, ANC > 2.000 mm3), renal (creatinine clearance > 60 mL/min), cardiac (VEF > 50%), and hepatic function (total serum bilirubin < 3 mg/dL, AST/ALT and gammaGT < 2.5 per upper normal limit value), within 1 week prior to study start (unless the abnormality is due to lymphoma involvement)
  7. Absence of symptomatic coronary artery disease, cardiac arrhythmias not well controlled with medication or myocardial infarction within the last 6 months (New York Heart Association Class III or IV heart disease)
  8. Absence of HIV infection
  9. No previous or concurrent malignancies with the exception of surgically cured carcinoma in-situ of the cervix and carcinoma of the skin and of other cancers without evidence of disease at least from 5 years
  10. Absence of any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
  11. Female patients must be non-pregnant and non-lactating. Sexually active patients of childbearing potential must implement adequate contraceptive measures during study participation
  12. No treatment with other experimental drugs within the 6 weeks previous to enrolment
  13. Give written informed consent prior to any study specific procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice

Exclusion Criteria:

  • NA

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: High-dose sequential chemoimmunotherapy
Two courses of methotrexate 3.5 g/mq day 1 and cytarabine 2 g/mq twice a day, for two days, Rituximab 375 mg/mq days 3 & 11 and Intrathecal liposomal cytarabine 50 mg day 6(Phase I) followed in case of response by cyclophosphamide 7 g/mq plus Rituximab 375 mg/mq and Intrathecal liposomal cytarabine 50 mg Leukapheresis A and cryopreservation (Phase II), Cytarabine 2 g/mq twice a day for 4 days, Rituximab 375 mg/m2 and Reinfusion of stem cells (Phase III), etoposide 2 g/mq, Intrathecal liposomal cytarabine 50 mg (Phase IV) and high-dose Thiotepa-BCNU supported by autologous stem cell transplant (Phase V), and whole-brain radiotherapy in patients who do not achieve a complete remission after chemotherapy (Phase VI)
Drug: High-dose sequential chemotherapy and autologous transplant
Two courses of methotrexate 3.5 g/mq day 1 and cytarabine 2 g/mq twice a day, for two days, Rituximab 375 mg/mq days 3 & 11 and Intrathecal liposomal cytarabine 50 mg day 6(Phase I) followed in case of response by cyclophosphamide 7 g/mq plus Rituximab 375 mg/mq and Intrathecal liposomal cytarabine 50 mg Leukapheresis A and cryopreservation (Phase II), Cytarabine 2 g/mq twice a day for 4 days, Rituximab 375 mg/m2 and Reinfusion of stem cells (Phase III), etoposide 2 g/mq, Intrathecal liposomal cytarabine 50 mg (Phase IV) and high-dose Thiotepa-BCNU supported by autologous stem cell transplant (Phase V), and whole-brain radiotherapy in patients who do not achieve a complete remission after chemotherapy (Phase VI)
Other Names:
  • Depocyte

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free Survival
Time Frame: 2-year
No new pathological events in a 2 ys follow-up period
2-year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Progression (TTP)
Time Frame: 2-year
Time elapsed from Lymphoma diagnosis and CNS involvement
2-year
Overall Survival
Time Frame: 5 Years
Patients alive after 5 years long follow-up
5 Years
Tolerability OF THE TREATMENT
Time Frame: 2-year
For the 38 patients enrolled the number of chemotherapy administered / expected during treatment period
2-year
Neurotoxicity
Time Frame: 2-year
Total number of patients with neurotoxic events during treatment
2-year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Andrés José Maria Ferreri

Collaborators

Mundipharma Pte Ltd.

Investigators

  • Study Chair: Andrés J. Ferreri, MD, San Raffaele Scientific Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2007

Primary Completion (Actual)

January 1, 2013

Study Completion (Actual)

January 1, 2013

Study Registration Dates

First Submitted

November 28, 2008

First Submitted That Met QC Criteria

December 2, 2008

First Posted (Estimated)

December 3, 2008

Study Record Updates

Last Update Posted (Actual)

December 10, 2024

Last Update Submitted That Met QC Criteria

November 22, 2024

Last Verified

November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SCNSL1
  • 2006-006999-38 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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