Dose Dense Chemotherapy and Rituximab for Young High Risk Diffuse Large B-Cell Lymphoma Patients (CRY-04)

NCT ID: NCT01502982

Last Updated: 2014-09-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

160 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-11-30

Study Completion Date

2014-05-31

Brief Summary

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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.

Detailed Description

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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

* After the 3rd course
* After the last course (within one month) of chemotherapy (biopsy if indicated)
* After radiotherapy (for patient given radiotherapy as part of the primary treatment)

Clinical follow-up:

* 4x per year during the first and second year of follow-up
* 2x per year during the third, fourth and fifth year of 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

Conditions

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Diffuse Large B-Cell Lymphoma

Keywords

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DLBCL high risk young

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Chemoimmunotherapy

Group Type EXPERIMENTAL

R-CHOEP14x6+HD-AraC+HD-Mtx

Intervention Type 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

Interventions

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R-CHOEP14x6+HD-AraC+HD-Mtx

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

Intervention Type DRUG

Other Intervention Names

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R-CHOEP14x6 HD-MTXx1 HD-AraCx1

Eligibility Criteria

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Inclusion Criteria

1. Age ≥ 18 - \< 65 years.
2. 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
3. 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.
4. Previously untreated.
5. Performance status \< 4 (Appendix 2).
6. Written informed consent

Exclusion Criteria

1. 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).
2. Impaired liver, renal or other organ function not caused by lymphoma, which will interfere with the treatment schedule.
3. Pregnancy.
4. 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.
5. Patients with other severe medical problems and with an expected short survival for non-lymphoma reasons.
6. Known HIV positivity.
7. Present or previous cancer except basal cell carcinoma and cervical carcinoma in situ.
8. Uncontrolled infectious disease.
9. Psychiatric or mental disorder which make the patient unable to give an informed consent and/or adhere to the protocol.
Minimum Eligible Age

18 Years

Maximum Eligible Age

64 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role collaborator

Nordic Lymphoma Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Harald Holte, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Oslo University Hospital

Locations

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Odense University Hospital

Odense, , Denmark

Site Status

Helsinki University central Hospital

Helsinki, , Finland

Site Status

Oslo University Hospital

Oslo, , Norway

Site Status

Lund University Hospital

Lund, , Sweden

Site Status

Countries

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Denmark Finland Norway Sweden

References

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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.

Reference Type DERIVED
PMID: 32079690 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24625556 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23247661 (View on PubMed)

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.

Reference Type DERIVED
PMID: 22882209 (View on PubMed)

Related Links

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http://www.nordic-lymphoma.org/

Nordic Lymphoma Group

Other Identifiers

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2004-003075-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NLG-LBC-04

Identifier Type: -

Identifier Source: org_study_id