NCT01502982

Brief Summary

The purpose is to test whether dose densified chemoimmunotherapy followed by central nervous system (CNS) prophylaxis for young high risk diffuse large B-cell lymphoma (DLBCL) patients is feasible and could improve time to treatment failure and reduce the risk of CNS relapses. Six courses of rituximab-cyclophosphamide-doxorubicin-etoposide-vincristine-prednison (R-CHOEP) given in two weeks intervals with the support of G-CSF is followed by one course of high dose methotrexate (HD-MTX) and high dose cytarabine (HD-Ara-C). The results will be compared to a historical Nordic study.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
160

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Nov 2004

Longer than P75 for phase_2

Geographic Reach
4 countries

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2004

Completed
7.1 years until next milestone

First Submitted

Initial submission to the registry

December 21, 2011

Completed
12 days until next milestone

First Posted

Study publicly available on registry

January 2, 2012

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2013

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2014

Completed
Last Updated

September 30, 2014

Status Verified

September 1, 2014

Enrollment Period

9.1 years

First QC Date

December 21, 2011

Last Update Submit

September 27, 2014

Conditions

Diffuse Large B-Cell Lymphoma

Keywords

DLBCLhigh riskyoung

Outcome Measures

Primary Outcomes (1)

  • Time to treatment failure

    Interval between the registration date and the date of documented progression or lack of response, first relapse, death for any reason or discontinuation/change of therapy because of toxicity, whichever occurs first. Otherwise, patients will be censored at the last date they were known to be alive. For patients not responding at any time point on study treatment, TTF is defined as 1 day.

    5 years

Secondary Outcomes (6)

  • Number of participants with adverse events

    Treatment period (5 years)

  • Clinical response rate

    Treatment period (5 years)

  • Time to progression

    5 years

  • Overall survival

    5 years

  • Incidence of CNS relapse

    Treatment period (5 years)

  • +1 more secondary outcomes

Study Arms (1)

Chemoimmunotherapy

EXPERIMENTAL
Drug: R-CHOEP14x6+HD-AraC+HD-Mtx

Interventions

R-CHOEP14x6+HD-AraC+HD-MtxDRUG

rituximab 375 mg/m2 day 1 cyclophosphamide 750 mg/m2 day 1 doxorubicin 50 mg/m2 day 1 vincristine 1.4 mg/m2 day 1 etoposide 100mg/m2 days 1,2,3 Prednison 100 mg days 1,2,3,4,5 cycle repeated six times every two weeks followed by HD-AraC 3g/m2x4 and HD-mtx 3 g/m2 HD-AraC 3g/m2x4 times every 12 h

Also known as: R-CHOEP14x6, HD-MTXx1, HD-AraCx1
Chemoimmunotherapy

Eligibility Criteria

Age18 Years - 64 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Age ≥ 18 - \< 65 years.
  • Histology verified according to the WHO classification and with CD20 positivity by immunhistochemistry or flow cytometry:
  • Diffuse large B-cell lymphomas with subgroups except posttransplantation-, Burkitt-like- and primary CNS lymphomas and cases with leptomeningeal lymphoma involvement. Morphologically discordant lymphomas (most often follicular lymphoma and diffuse large cell B-cell lymphoma in different biopsy specimens, e.g. lymphatic gland and bone marrow) and transformed lymphomas are not to be included.
  • Follicular lymphomas grade III The diagnosis made by the local pathologist of the participating centre will be accepted for registration
  • Patients in at least stage II with age adjusted IPI score of 2 or 3:
  • Stage III /IV and elevated LDH and/or WHO performance status 2 - 3 Stage II and elevated LDH and WHO performance status 2 - 3.
  • Previously untreated.
  • Performance status \< 4 (Appendix 2).
  • Written informed consent

You may not qualify if:

  • Severe cardiac disease: cardiac function grade 3-4 (Appendix 2) or Left Ventricular Ejection Fraction (LVEF) \< 45% (based on MUGA scintigraphy or echo Doppler cardiography).
  • Impaired liver, renal or other organ function not caused by lymphoma, which will interfere with the treatment schedule.
  • Pregnancy.
  • Men and women of reproductive potential not agreeing to use an acceptable method of birth control during treatment and for six months after completion of treatment.
  • Patients with other severe medical problems and with an expected short survival for non-lymphoma reasons.
  • Known HIV positivity.
  • Present or previous cancer except basal cell carcinoma and cervical carcinoma in situ.
  • Uncontrolled infectious disease.
  • Psychiatric or mental disorder which make the patient unable to give an informed consent and/or adhere to the protocol.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Odense University Hospital

Odense, Denmark

Location

Helsinki University central Hospital

Helsinki, Finland

Location

Oslo University Hospital

Oslo, Norway

Location

Lund University Hospital

Lund, Sweden

Location

Related Publications (4)

  • Autio M, Leivonen SK, Bruck O, Mustjoki S, Meszaros Jorgensen J, Karjalainen-Lindsberg ML, Beiske K, Holte H, Pellinen T, Leppa S. Immune cell constitution in the tumor microenvironment predicts the outcome in diffuse large B-cell lymphoma. Haematologica. 2021 Mar 1;106(3):718-729. doi: 10.3324/haematol.2019.243626.

    PMID: 32079690DERIVED

  • Taskinen M, Louhimo R, Koivula S, Chen P, Rantanen V, Holte H, Delabie J, Karjalainen-Lindsberg ML, Bjorkholm M, Fluge O, Pedersen LM, Fjorden K, Jerkeman M, Eriksson M, Hautaniemi S, Leppa S. Deregulation of COMMD1 is associated with poor prognosis in diffuse large B-cell lymphoma. PLoS One. 2014 Mar 13;9(3):e91031. doi: 10.1371/journal.pone.0091031. eCollection 2014.

    PMID: 24625556DERIVED

  • Holte H, Leppa S, Bjorkholm M, Fluge O, Jyrkkio S, Delabie J, Sundstrom C, Karjalainen-Lindsberg ML, Erlanson M, Kolstad A, Fossa A, Ostenstad B, Lofvenberg E, Nordstrom M, Janes R, Pedersen LM, Anderson H, Jerkeman M, Eriksson M. Dose-densified chemoimmunotherapy followed by systemic central nervous system prophylaxis for younger high-risk diffuse large B-cell/follicular grade 3 lymphoma patients: results of a phase II Nordic Lymphoma Group study. Ann Oncol. 2013 May;24(5):1385-92. doi: 10.1093/annonc/mds621. Epub 2012 Dec 17.

    PMID: 23247661DERIVED

  • Riihijarvi S, Nurmi H, Holte H, Bjorkholm M, Fluge O, Pedersen LM, Rydstrom K, Jerkeman M, Eriksson M, Leppa S. High serum vascular endothelial growth factor level is an adverse prognostic factor for high-risk diffuse large B-cell lymphoma patients treated with dose-dense chemoimmunotherapy. Eur J Haematol. 2012 Nov;89(5):395-402. doi: 10.1111/ejh.12005. Epub 2012 Sep 14.

    PMID: 22882209DERIVED

Related Links

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Condition Hierarchy (Ancestors)

Lymphoma, B-CellLymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Study Officials

  • Harald Holte, MD, PhD

    Oslo University Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NETWORK
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 21, 2011

First Posted

January 2, 2012

Study Start

November 1, 2004

Primary Completion

December 1, 2013

Study Completion

May 1, 2014

Last Updated

September 30, 2014

Record last verified: 2014-09

Locations

DK(1)NO(1)SE(1)FI(1)