NCT01325194

Brief Summary

The purpose is to test whether early central nervous system (CNS) prophylaxis given at the beginning of therapy for young high risk diffuse large B-cell lymphoma (DLBCL) patients is feasible and could reduce the risk of CNS relapses. Early CNS prophylaxis with two courses high dose methotrexate (HD-MTX) in combination with rituximab-cyclophosphamide-doxorubicin-vincristine-prednison (R-CHOP) is followed by four courses of R-CHOP14 and etoposide (E) and one course of HD-Ara-C. In addition the patients will receive three courses of liposomal cytarabine intrathecally. The results will be compared to a recent Nordic CRY-04 study. Shifting of CNS prophylaxis to the beginning of the therapy offers a potential to overcome the subclinical disease and thus reduce the risk of early clinical CNS recurrence. As flow cytometry (FCM) can improve the sensitivity for detecting occult leptomeningeal disease over cytology , FCM from cerebrospinal fluid will be incorporated into the staging procedures.

Trial Health

90
On Track

Trial Health Score

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

Enrollment
143

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Mar 2011

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

March 1, 2011

Completed
13 days until next milestone

First Submitted

Initial submission to the registry

March 14, 2011

Completed
15 days until next milestone

First Posted

Study publicly available on registry

March 29, 2011

Completed
7.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2018

Completed
1.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2019

Completed
Last Updated

March 3, 2020

Status Verified

March 1, 2020

Enrollment Period

7.7 years

First QC Date

March 14, 2011

Last Update Submit

March 2, 2020

Conditions

Primary Disease

Keywords

DLBCLFL grade 3Bhigh riskCNS prophylaxischemoimmunotherapy

Outcome Measures

Primary Outcomes (1)

  • Time to treatment failure

    3 and 5 years

Secondary Outcomes (8)

  • Maximal hematological, gastrointestinal, neuronal and other toxicities

    Treatment period (5 years)

  • Clinical response rate

    Treatment period (5 years)

  • Incidence of central nervous system(CNS) relapse in cerebrospinal fluid (CSF )cytology neg/flow cytometry positive cases

    3 and 5 years

  • Incidence of CNS relapse in a subgroup of patients with more than one extranodal site and elevated lactate dehydrogenase (LDH)

    3 and 5 years

  • Progression free survival

    3 and 5 years

  • +3 more secondary outcomes

Study Arms (1)

CNS prophylaxis

EXPERIMENTAL
Drug: liposomal cytarabine

Interventions

liposomal cytarabineDRUG

50 mg intrathecally three times

Also known as: Depocyte
CNS prophylaxis

Eligibility Criteria

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

You may qualify if:

  • Age ≥ 18 - \< 65 years. Histologically confirmed CD20+ diffuse large B-cell lymphoma (DLBCL) based on WHO 2008 Lymphoma Classification
  • Follicular lymphomas (FLs) grade 3b is allowed
  • Patients in at least stage II with age adjusted international prognostic score (IPI score) of 2 or 3:
  • Stage III /IV and elevated LDH
  • Stage III/IV and WHO performance status 2 - 3
  • Stage II and elevated LDH and WHO performance status 2 - 3 And/or patients with
  • More than one extranodal site
  • Testicular lymphoma, stage IIE and higher
  • Paranasal sinus and orbital lymphoma with destruction of bone
  • Large cell infiltration of the bone marrow

You may not qualify if:

  • Severe cardiac disease: cardiac function grade 3-4
  • Impaired liver, renal or other organ function not caused by lymphoma, which will interfere with the treatment schedule
  • Pregnancy/lactation
  • 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
  • Uncontrolled infectious disease, including meningeal infection
  • Active cancer except basal cell carcinoma and cervical carcinoma in situ during the last five years
  • Earlier treatment containing anthracyclins
  • Psychiatric or mental disorder which make the patient unable to give an informed consent and/or adhere to the protocol
  • CNS disease as diagnosed by MRI or cerebrospinal fluid (CSF) cytology. Positive CSF flow cytometry below diagnostic threshold level by cytology is allowed
  • Pleural or peritoneal fluid that cannot be drained safely
  • Hypersensitivity to the active substance or any of the other ingredients
  • Patients participating in other clinical studies, unless followed for survival

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Department of Hematology, Århus University Hospital

Aarhus, Denmark

Location

Department of Oncology, Helsinki University Central Hospital

Helsinki, Finland

Location

Department of Oncology, Oslo University Hospital

Oslo, Norway

Location

Department of Oncology, Lund University Hospital

Lund, Sweden

Location

Related Publications (4)

  • Arffman M, Meriranta L, Autio M, Holte H, Jorgensen J, Brown P, Jyrkkio S, Jerkeman M, Drott K, Fluge O, Bjorkholm M, Karjalainen-Lindsberg ML, Beiske K, Pedersen MO, Leivonen SK, Leppa S. Inflammatory and subtype-dependent serum protein signatures predict survival beyond the ctDNA in aggressive B cell lymphomas. Med. 2024 Jun 14;5(6):583-602.e5. doi: 10.1016/j.medj.2024.03.007. Epub 2024 Apr 4.

    PMID: 38579729DERIVED

  • Vajavaara H, Leivonen SK, Jorgensen J, Holte H, Leppa S. Low lymphocyte-to-monocyte ratio predicts poor outcome in high-risk aggressive large B-cell lymphoma. EJHaem. 2022 Jun 23;3(3):681-687. doi: 10.1002/jha2.409. eCollection 2022 Aug.

    PMID: 36051040DERIVED

  • Leppa S, Jorgensen J, Tierens A, Meriranta L, Ostlie I, de Nully Brown P, Fagerli UM, Larsen TS, Mannisto S, Munksgaard L, Maisenholder M, Vasala K, Meyer P, Jerkeman M, Bjorkholm M, Fluge O, Jyrkkio S, Liestol K, Ralfkiaer E, Spetalen S, Beiske K, Karjalainen-Lindsberg ML, Holte H. Patients with high-risk DLBCL benefit from dose-dense immunochemotherapy combined with early systemic CNS prophylaxis. Blood Adv. 2020 May 12;4(9):1906-1915. doi: 10.1182/bloodadvances.2020001518.

    PMID: 32380536DERIVED

  • 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

Related Links

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

March 14, 2011

First Posted

March 29, 2011

Study Start

March 1, 2011

Primary Completion

November 1, 2018

Study Completion

December 31, 2019

Last Updated

March 3, 2020

Record last verified: 2020-03

Locations

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