Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2004-003075-37 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Amgen | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Pathology:
Patients may be included on the bases of the histological diagnosis of the local pathologist. The specimen will be reviewed by a central pathologist in each country
Treatment:
All patients receive CHOEP-14 with rituximab x 6 with the support of G-CSF followed by high dose cytarabine i.v. and high dose methotrexate i.v.Intrathecal (i.t.) CNS prophylaxis in combination with chemotherapy is not to be given, but i.t. methotrexate may be given once after initial liquid sampling. Radiotherapy will be given at the discretion of the individual centres.
Investigations before, during and after treatment:
The disease status will be assessed prior to treatment start, after 3 cycles of CHOEP + rituximab and after completion of the treatment schedule. Positron Emission Tomography (PET) using F18 deoxyglucose may be performed after fulfillment of treatment. Persistent, suspected lymphoma tissue should whenever possible be confirmed with a biopsy, otherwise the patient will be regarded as PR and second line therapy will be considered (see schematic outline).
Clinical and radiological (CT) assessment are performed at pretreatment and subsequently on sites initially involved, and bone marrow biopsy if initially involved
Clinical follow-up:
Radiological investigations at follow up:
-CT after 6, 12 and 24 months of sites initially involved. CT abdomen in all cases after 12 and 24 months. X-ray of the thorax (if CT thorax is performed) after 6, 12 and 24 months
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Chemoimmunotherapy | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| R-CHOEP14x6+HD-AraC+HD-Mtx | Drug | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with adverse events | Grade 2-4 hematological and non-hematological adverse events according to the WHO Common Toxicity Criteria as specified in the protocol | Treatment period (5 years) |
| Clinical response rate |
Not provided
Inclusion Criteria:
Age ≥ 18 - < 65 years.
Histology verified according to the WHO classification and with CD20 positivity by immunhistochemistry or flow cytometry:
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
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Harald Holte, MD, PhD | Oslo University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Odense University Hospital | Odense | Denmark | ||||
| Helsinki University central Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32079690 | Derived | 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. | |
| 24625556 | Derived |
| Label | URL |
|---|---|
| Nordic Lymphoma Group | View source |
Not provided
Not provided
| ID | Term |
|---|---|
| D016403 | Lymphoma, Large B-Cell, Diffuse |
| ID | Term |
|---|---|
| D016393 | Lymphoma, B-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
Number of patients with complete and partial responses, stable or progressive disease after 3 courses and the end of treatment period
| Treatment period (5 years) |
| Time to progression | Time from registration to the date of disease progression. Otherwise, the patients are censored at the last date of follow up. Patients still alive in a complete response or lost to follow-up are censored at the last date they were known to be alive. Patients who die due to causes other than lymphoma are censored at the date of death | 5 years |
| Overall survival | Time from the registration date to the date of death. Patients still alive or lost to follow-up are censored at the last date they were known to be alive. | 5 years |
| Incidence of CNS relapse | Treatment period (5 years) |
| Molecular factors important for clinical outcome | Treatment period (5 years) |
| Helsinki |
| Finland |
| Oslo University Hospital | Oslo | Norway |
| Lund University Hospital | Lund | Sweden |
| 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. |
| 23247661 | Derived | 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. |
| 22882209 | Derived | 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. |
| D009369 |
| Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |