HOVON 127 BL / SAKK 37/16: Phase III study comparing 2 treatments (R-CODOX-M/R-IVAC versus DA-EPOCH-R) in patients with Burkitt lymphoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Haemato Oncology Foundation For Adults Netherlands

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

19 Jun 2014 → ongoing

Decision date (initial)

2024-09-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

KWF Dutch Cancer Society

External identifiers

EU CT number

2023-503423-25-00

EudraCT number

2013-004394-27

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To confirm in a multicenter setting an improvement in PFS to 85% at 2 years of DA-EPOCH-R in patients with newly diagnosed high risk Burkitt lymphoma as compared to an expected PFS of 70% at 2 years for the control arm R-CODOX-M/R-IVAC

Secondary objectives 3

1. To evaluate Overall Response Rate (ORR) end-of-treatment, Event Free Survival (EFS) and Overall Survival (OS) at 2 years
2. To evaluate both regimens with respect to CTCAE grade ≥ 3 toxicity
3. To evaluate both regimens with respect to hospitalization days

Conditions and MedDRA coding

Burkitt lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. First diagnosis of high risk Burkitt lymphoma (sporadic and HIV associated), histologically confirmed according to the WHO classification 2008. Upon its availability the WHO 2016 classification should be used, to replace the WHO 2008 classification
2. High risk disease; i.e. any of following: elevated LDH, WHO performance status ≥ 2 (appendix C), Ann Arbor stage III or IV (Appendix A), tumour mass ≥ 10 cm
3. Age 18-75 years inclusive
4. WHO performance status (PS) 0-3, WHO PS 4 only if disease related (Appendix C)
5. Written informed consent

Exclusion criteria 17

1. All histopathological diagnoses other than Burkitt lymphoma according to the WHO classification 2008, irrespective of the presence of a MYC rearrangement; Upon its availability the WHO 2016 classification should be used, to replace the WHO 2008 classification
2. Patients with endemic Burkitt lymphoma
3. Patients with low risk Burkitt lymphoma (i.e. all of following: normal LDH, WHO performance status 0 or 1 (appendix C), Ann Arbor stage I or II (Appendix A), no tumour mass ≥ 10 cm)
4. Patients with CNS localization of Burkitt lymphoma
5. Prior treatment other than local radiation (max. 10 Gy) or short course (max 7 days) of steroids ≤ 1 mg/kg or ≤100mg predniso(lo)ne (whichever is greater; or equivalent corticosteroid) or acute symptoms; or 1 cycle of R-CHOP
6. Creatinine clearance < 50 ml/min unless lymphoma related
7. Inadequate hepatic function: bilirubin > 2.5 * ULN (total) except patients with Gilbert's syndrome as defined by > 80% unconjugated
8. Inadequate haematological function ANC < 1x10^9/l and platelets < 75x10^9 /l unless lymphoma related
9. Severe pulmonary dysfunction (CTCAE grade 3-4, see Appendix D)
10. Severe neurological or psychiatric disease
11. Active symptomatic ischemic heart disease, myocardial infarction, or congestive heart failure within the past year. If an ultrasound or MUGA scan is obtained the LVEF should exceed 45%
12. All men and all women of child-bearing potential not willing or able to use an acceptable method of birth control for the duration of the study and one year beyond treatment completion
13. Female subject pregnant or breast-feeding
14. History of a prior invasive malignancy in the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma
15. Serious concomitant medical illnesses that would jeopardize the patient's ability to receive the regimen with reasonable safety, includig active hepatitis B (HBV, see also paragraph 9.3) or hepatitis C (HCV) infection
16. Current participation in another clinical trial interfering with HO127
17. Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 2-year PFS; defined as time from randomisation to disease progression, relapse or death, whichever comes first. Patients still alive or lost to follow up are censored at the date they were last known to be alive

Secondary endpoints 5

1. ORR end-of-treatment
2. EFS at 2 years; defined as time from randomisation to first event (death from any cause, no CR, relapse, whichever comes first).
3. OS at 2 years; defined as time from randomisation until death from any cause; patients still alive or lost to follow up are censored at the date they were last known to be alive
4. Rate of CTCAE grade ≥3 toxicities
5. Number of hospitalization days

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 9

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Haemato Oncology Foundation For Adults Netherlands

Sponsor organisation

Haemato Oncology Foundation For Adults Netherlands

Address

S Gravendijkwal 230

City

Rotterdam

Postcode

3015 CE

Country

Netherlands

Scientific contact point

Organisation

Haemato Oncology Foundation For Adults Netherlands

Contact name

M.E.D. Chamuleau

Public contact point

Organisation

Haemato Oncology Foundation For Adults Netherlands

Contact name

M.C. Breems - de Ridder

Third parties 1

Locations

2 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 18 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications