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

Primary Purpose

B-Cell Lymphomas

Status
Unknown status
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
High-dose sequential chemotherapy and autologous transplant
Sponsored by
IRCCS San Raffaele
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for B-Cell Lymphomas focused on measuring B-cell lymphomas, lymphomatous meningitis, liposomal cytarabine, autologous transplant, CNS involvement, Secondary CNS lymphomas

Eligibility Criteria

19 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • San Raffaele Scientific InstituteRecruiting
  • San Raffaele Scientific InstituteRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

High-dose sequential chemoimmunotherapy

Arm Description

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)

Outcomes

Primary Outcome Measures

Event-free survival

Secondary Outcome Measures

Response duration
Overall survival
Tolerability
Neurotoxicity

Full Information

First Posted
November 28, 2008
Last Updated
December 2, 2008
Sponsor
IRCCS San Raffaele
Collaborators
Mundipharma K.K.
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1. Study Identification

Unique Protocol Identification Number
NCT00801216
Brief Title
High-Dose Sequential Chemoimmunotherapy for B-Cell Lymphomas With Central Nervous System Involvement
Acronym
SCNSL1
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2008
Overall Recruitment Status
Unknown status
Study Start Date
January 2007 (undefined)
Primary Completion Date
January 2010 (Anticipated)
Study Completion Date
January 2012 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor
IRCCS San Raffaele
Collaborators
Mundipharma K.K.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B-Cell Lymphomas
Keywords
B-cell lymphomas, lymphomatous meningitis, liposomal cytarabine, autologous transplant, CNS involvement, Secondary CNS lymphomas

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
38 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
High-dose sequential chemoimmunotherapy
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
High-dose sequential chemotherapy and autologous transplant
Other Intervention Name(s)
Depocyte
Intervention Description
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)
Primary Outcome Measure Information:
Title
Event-free survival
Time Frame
2-year
Secondary Outcome Measure Information:
Title
Response duration
Time Frame
2-year
Title
Overall survival
Time Frame
2-year
Title
Tolerability
Time Frame
2-year
Title
Neurotoxicity
Time Frame
2-year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed diagnosis of diffuse large-cell, follicular or mantle cell lymphoma CNS involvement (brain, meninges, cranial nerves, eyes, and/or spinal cord) at diagnosis or relapse after conventional chemotherapy Diagnosis of CNS involvement either by brain biopsy or CSF cytology examination. Neuroimaging alone is acceptable only when stereotactic biopsy is formally contraindicated. Age 19-65 years ECOG performance status 0-3 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) 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) Absence of HIV infection 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 Absence of any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule Female patients must be non-pregnant and non-lactating. Sexually active patients of childbearing potential must implement adequate contraceptive measures during study participation No treatment with other experimental drugs within the 6 weeks previous to enrolment 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Andrés J. Ferreri, MD
Phone
0039-02-2643 7649
Email
andres.ferreri@hsr.it
First Name & Middle Initial & Last Name or Official Title & Degree
Stefania Trinca
Phone
0039-02-2643 4289
Email
stefania.trinca@hsr.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrés J. Ferreri, MD
Organizational Affiliation
San Raffaele Scientific Institute
Official's Role
Study Chair
Facility Information:
Facility Name
San Raffaele Scientific Institute
City
Milan
ZIP/Postal Code
20132
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Roberto Crocchiolo, MD
Email
roberto.crocchiolo@hsr.it
First Name & Middle Initial & Last Name & Degree
Silvia Govi, MD
Email
silvia.govi@hsr.it
First Name & Middle Initial & Last Name & Degree
Andrea Assanelli, MD
Facility Name
San Raffaele Scientific Institute
City
Milan
ZIP/Postal Code
20132
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Roberto Crocchiolo, MD
First Name & Middle Initial & Last Name & Degree
Silvia Govi, MD

12. IPD Sharing Statement

Citations:
PubMed Identifier
26282634
Citation
Ferreri AJ, Donadoni G, Cabras MG, Patti C, Mian M, Zambello R, Tarella C, Di Nicola M, D'Arco AM, Doa G, Bruno-Ventre M, Assanelli A, Foppoli M, Citterio G, Fanni A, Mule A, Caligaris-Cappio F, Ciceri F. High Doses of Antimetabolites Followed by High-Dose Sequential Chemoimmunotherapy and Autologous Stem-Cell Transplantation in Patients With Systemic B-Cell Lymphoma and Secondary CNS Involvement: Final Results of a Multicenter Phase II Trial. J Clin Oncol. 2015 Nov 20;33(33):3903-10. doi: 10.1200/JCO.2015.61.1236. Epub 2015 Aug 17.
Results Reference
derived

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

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