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

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

First Received on November 28, 2008.  
Last Updated on December 2, 2008  
History of Changes
This Clinical Trial Sponsored By: IRCCS San Raffaele
Collaborator: Mundipharma K.K.
Information provided by: IRCCS San Raffaele
ClinicalTrials.gov Identifier: NCT00801216
 

Purpose for Clinical Trial

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 Study Intervention Clinical Trial 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: Study Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
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:

MedlinePlus related topics:
Lymphoma
Drug Information available for:
Cytarabine
Rituximab

U.S. FDA Resources

Further study details as provided by IRCCS San Raffaele:

Primary Outcome Measures For Clinical Trial:

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

Secondary Outcome Measures For Clinical Trial:

  • 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 Study 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

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

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