High-Dose Sequential Chemoimmunotherapy for B-Cell Lymphomas With Central Nervous System Involvement (SCNSL1)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2008 by IRCCS San Raffaele.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Mundipharma K.K.
Information provided by:
IRCCS San Raffaele
ClinicalTrials.gov Identifier:
NCT00801216
First received: November 28, 2008
Last updated: December 2, 2008
Last verified: October 2008
  Purpose

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.


Condition Intervention Phase
B-Cell Lymphomas
Drug: High-dose sequential chemotherapy and autologous transplant
Phase 2

IRCCS San Raffaele has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.  

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: High-Dose Sequential Chemotherapy and Rituximab (R-HDS) in Patients With Systemic B-Cell Lymphoma With Central Nervous System Involvement at Diagnosis or Relapse

Resource links provided by NLM:


Further study details as provided by IRCCS San Raffaele:

Primary Outcome Measures:
  • Event-free survival [ Time Frame: 2-year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Response duration [ Time Frame: 2-year ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: 2-year ] [ Designated as safety issue: Yes ]
  • Tolerability [ Time Frame: 2-year ] [ Designated as safety issue: Yes ]
  • Neurotoxicity [ Time Frame: 2-year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 38
Study Start Date: January 2007
Estimated Study Completion Date: January 2012
Estimated Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Depocyte

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.

  Eligibility

Ages Eligible for Study:   19 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 19-65 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
  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: NCT00801216

Contacts
Contact: Andrés J. Ferreri, MD 0039-02-2643 7649 andres.ferreri@hsr.it
Contact: Stefania Trinca 0039-02-2643 4289 stefania.trinca@hsr.it

Locations
Italy
San Raffaele Scientific Institute Recruiting
Milan, Italy, 20132
Contact: Roberto Crocchiolo, MD       roberto.crocchiolo@hsr.it   
Contact: Silvia Govi, MD       silvia.govi@hsr.it   
Sub-Investigator: Andrea Assanelli, MD         
San Raffaele Scientific Institute Recruiting
Milan, Italy, 20132
Sub-Investigator: Roberto Crocchiolo, MD         
Sub-Investigator: Silvia Govi, MD         
Sponsors and Collaborators
IRCCS San Raffaele
Mundipharma K.K.
Investigators
Study Chair: Andrés J. Ferreri, MD San Raffaele Scientific Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Andrés J.M. Ferreri, San Raffaele Scientific Institute
ClinicalTrials.gov Identifier: NCT00801216     History of Changes
Other Study ID Numbers: SCNSL1, IIL-SCNSL-1
Study First Received: November 28, 2008
Last Updated: December 2, 2008
Health Authority: United States: Food and Drug Administration
Italy: Ministry of Health

Keywords provided by IRCCS San Raffaele:
B-cell lymphomas
lymphomatous meningitis
liposomal cytarabine
autologous transplant
CNS involvement
Secondary CNS lymphomas

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cytarabine
Rituximab
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 28, 2014