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

NCT00801216 | Completed Phase 2 Results DMC

• 2 other identifiers: SCNSL12006-006999-38
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

B-cell Lymphomas

Keywords

B-cell lymphomas; lymphomatous meningitis; liposomal cytarabine; autologous transplant; CNS involvement; Secondary CNS lymphomas

Outcome Measures

Primary Outcomes (1)

• Event-free Survival

  No new pathological events in a 2 ys follow-up period

  2-year

Secondary Outcomes (4)

• Time to Progression (TTP)

  2-year

• Overall Survival

  5 Years

• Tolerability OF THE TREATMENT

  2-year

• Neurotoxicity

  2-year

Study Arms (1)

High-dose sequential chemoimmunotherapy

EXPERIMENTAL

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

Interventions

High-dose sequential chemotherapy and autologous transplant DRUG

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)

Also known as: Depocyte

High-dose sequential chemoimmunotherapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 18-70 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

Sponsors & Collaborators

• Andrés José Maria Ferreri: lead
• Mundipharma Pte Ltd.: collaborator

Study Sites (1)

San Raffaele Scientific Institute

Milan, 20132, Italy

Location

Related Publications (1)

• 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.

  PMID: 26282634 DERIVED

Related Links

• Intergruppo Italiano Linfomi web site

MeSH Terms

Conditions

Lymphoma, B-Cell; Meningeal Carcinomatosis

Interventions

Transplantation, Autologous

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. Andrés José Maria Ferreri
• Organization: IRCCS Ospedale San Raffaele

ferreri.clinicaltrials@hsr.it

022643 7649

Study Officials

• Andrés J. Ferreri, MD

  San Raffaele Scientific Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: November 28, 2008
• First Posted: December 3, 2008
• Study Start: January 1, 2007
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: December 10, 2024
• Results First Posted: December 10, 2024

Record last verified: 2024-11

Locations

IT (1)