Biomarker Driven Intensified ChemoImmunotherapy With Early CNS Prophylaxis

NCT03293173 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: NLG-LBC-06
• Study Type: interventional
• Target: 120
• Locations: 4 countries
• Sites: 16

Brief Summary

This study is testing whether stratification of the patients according to biological risk factors for different treatment groups will improve the outcome of patients with clinically high diffuse large B-cell lymphoma (DLBCL).

Conditions

Lymphoma, Large B-Cell, Diffuse

Keywords

DLBCL; Chemoimmunotherapy; High risk; CNS prophylaxis; Biomarker-driven

Outcome Measures

Primary Outcomes (1)

• Time to treatment failure (TTF) of the patients with biological risk factors

  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 one day.

  At 3 years

Secondary Outcomes (7)

• Time to treatment failure (TTF) at 3 years from date of registration of all patients and the patients in the low risk group

  At 3 years

• Incidence of treatment-emergent adverse events (Safety and tolerability)

  During the treatment period at the end of each cycle (14 or 21 days) up to 6 months. In addition, severe late toxicities during follow-up at 6 months intervals through study completion, an average of 5.5 years.

• Clinical response rate of all patients and the patients with biological risk factors

  At the end of treatment cycles 2 and 7. Each cycle is two (group A) or three weeks (group B)

• CNS relapse rate

  At 1,5 years

• Progression free survival rate (PFS) of all patients and the patients with biological risk factors

  At 3 years

Study Arms (2)

Group A

EXPERIMENTAL

Biologically low risk group, R-CHOEP-14

Combination Product: R-CHOEP

Group B

EXPERIMENTAL

Biologically high risk group, DA-EPOCH-R

Combination Product: DA-EPOCH-R

Interventions

R-CHOEP COMBINATION_PRODUCT

rituximab, cyclophosphamide, doxorubicin, etoposide, vincristine, prednisone

Group A

DA-EPOCH-R COMBINATION_PRODUCT

dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab

Group B

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18 - 64 years
• Histologically confirmed CD20+ DLBCL based on revised WHO 2008 Lymphoma Classification. The following subgroups and variants can be included:
• ALK-positive large B-cell lymphoma
• Intravascular large B-cell lymphoma
• T-cell rich B-cell lymphoma
• Myc/BCL-2 double hit lymphoma
• Follicular lymphomas grade 3b
• DLBCL with previously undiagnosed concurrent small cell infiltration in bone marrow, lymph node, or extranodal site and lymphomas intermediate between DLBCL and Burkitt's lymphoma are allowed
• Posttransplantation lymphoma (PTLD), discordant or transformed lymphoma are NOT allowed
• Patients in at least stage II with age adjusted 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 site specific risk factors for CNS recurrence defined as follows
• More than one extranodal site

You may not qualify if:

• Severe cardiac disease: cardiac function grade 3-4, left ventricular ejection fraction \<45%
• Impaired bone marrow liver, renal or other organ function not caused by lymphoma, which will interfere with the treatment schedule (Hemoglobin \< 9 g/dL, ANC \< 1.5 × 109/L, Platelet count \< 75 × 109/L, creatinine clearance \< 40 mL/min, ALT/AST \> 2.5 x ULN, bilirubin 1.5 x ULN, INR \> 1.5)
• Pregnancy/lactation
• Men and women of reproductive potential not agreeing to use effective contraception during treatment and for 18 months after completion of treatment (Effective contraception is combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable), intrauterine device (IUD), hormone-releasing IUD, bilateral tubal occlusion, vasectomised partner, or sexual abstinence
• Patients with other severe medical problems, including active infections, cardiac or pulmonary disease, history of PML and with an expected short survival for non-lymphoma reasons
• Known HIV positivity
• Active or chronic hepatitis B virus (HBV) infection (defined as positive HBsAg serology), or active hepatitis C virus (HCV) infection (defined by antibody serology testing). HBsAg, HBcAb, and HCVAb must be tested during screening. Patients who have protective titers of HBsAb along negative HBsAg after vaccination or prior but cured hepatitis B are eligible.
• Vaccination with a live vaccine within one month prior to randomization
• Patients with a malignancy that has been treated but not with curative intent, unless the malignancy has been in remission without treatment for ≥ 5 years prior to enrollment
• Earlier treatment containing anthracyclines
• 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 CSF cytology. Positive CSF flow cytometry below diagnostic threshold level by cytology is allowed
• Transformed lymphoma
• Primary mediastinal B-cell lymphoma
• Pleural or peritoneal fluid that cannot be drained safely

Sponsors & Collaborators

• Nordic Lymphoma Group: lead
• Helsinki University Central Hospital: collaborator
• Aarhus University Hospital: collaborator

Study Sites (16)

Aarhus University Hospital

Aarhus, Denmark

Location

Dept of Haematology, Rigshospitalet

Copenhagen, 2100, Denmark

Location

Dept of Haematology, Herlev Hospital, Copenhagen

Herlev, Denmark

Location

Dept haematology, Odense University hospital

Odense, 5000, Denmark

Location

Dept of Haematology, Sjaellands University hospital, Roskilde

Roskilde, 4000, Denmark

Location

Helsinki University Hospital Cancer Centre

Helsinki, 00029, Finland

Location

Keski-Suomen keskussairaala

Jyväskylä, 40620, Finland

Location

Kuopio University Hospital

Kuopio, 70029, Finland

Location

TAYS

Tampere, 33521, Finland

Location

Turku University Hospital, Syöpäklinikka

Turku, 20520, Finland

Location

Dept. of Oncology, Helse Bergen HF Haukeland sykehus

Bergen, 5021, Norway

Location

Oslo University Hospital

Oslo, Norway

Location

Dept. of Haematology and Oncology, Helse Stavander HF sykehuset

Stavanger, 4011, Norway

Location

Dept. of Oncology, Universitetssykehuset i Nord-Norge HF

Tromsø, 9038, Norway

Location

Dept of Oncology, St. Olavs hospital HF

Trondheim, 7006, Norway

Location

Skåne University Hospital

Lund, Sweden

Location

Related Publications (3)

• Fiskvik I, Beiske K, Delabie J, Yri O, Spetalen S, Karjalainen-Lindsberg ML, Leppa S, Liestol K, Smeland EB, Holte H. Combining MYC, BCL2 and TP53 gene and protein expression alterations improves risk stratification in diffuse large B-cell lymphoma. Leuk Lymphoma. 2015 Jun;56(6):1742-9. doi: 10.3109/10428194.2014.970550. Epub 2014 Nov 19.

  PMID: 25284491 BACKGROUND

• 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: 23247661 BACKGROUND

• 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: 38579729 DERIVED

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Sirpa Leppa, prof

  Helsinki University Hospital Cancer Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: Stratification into group A (standard) or group B (experimental) based on biological risk factors

Study Record Dates

• First Submitted: September 5, 2017
• First Posted: September 26, 2017
• Study Start: August 4, 2017
• Primary Completion: January 31, 2021
• Study Completion: December 31, 2024
• Last Updated: June 21, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Beginning 3 months and ending 5 years following article publication
• Access Criteria: Researchers who provide a methodologically sound proposal.

Locations

FI (5); DK (5); NO (5); SE (1)