The main objective of the trial is to show that ABVD-based response-adapted therapy for advanced-stage Hodgkin lymphoma, with treatment intensification (BEACOPP) in case of a positive FDG-PET after one cycle of ABVD, has non-inferior efficacy…
ID
Source
Brief title
Condition
- Lymphomas Hodgkin's disease
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Freedom from treatment failure (FFTF)
Secondary outcome
* Response at the end of therapy (chemotherapy and radiotherapy, whenever
applicable);
* Progression-free survival (PFS) ;
* Overall survival ;
* Serum TARC levels at baseline, during treatment and follow up;
* Frequency of acute toxicity and long-term toxicity in terms of second
malignancies, cardiovascular and pulmonary events.
Background summary
Escalated BEACOPP is currently considered to be the standard treatment in
advanced Hodgkin Lymphoma in a large number of centers. Escalated BEACOPP is
more effective than ABVD. However, the disadvantage of treating patients with
escalated BEACOPP is the higher risk of serious acute and late side effects
compared with ABVD. A clinical trial is therefore needed to identify those
patients who can reliably be treated with the less intense ABVD schedule and
those who need more intense treatment.
Study objective
The main objective of the trial is to show that ABVD-based response-adapted
therapy for advanced-stage Hodgkin lymphoma, with treatment intensification
(BEACOPP) in case of a positive FDG-PET after one cycle of ABVD, has
non-inferior efficacy compared with the intensive BEACOPP regimen.
Secondary objectives include the assessment of the prognostic value of PET
after one cycle of BEACOPPesc; of the predictive and prognostic value of serum
TARC levels as tumor marker; of treatment related toxicities with a focus on
second malignancies, pulmonary toxicities and cardiotoxicity during therapy and
during (long term) follow up.
Study design
All patients will have a baseline FDG-PET/CT and diagnostic quality CT scan
prior to randomization. All patients will be randomized between:
1. An experimental arm (very early PET-response adapted), where all patients
are initially treated with a single cycle of ABVD, followed by Very early
FDG-PET/CT and if negative patients continue on ABVD therapy to a total of six
cycles. Very early FDG-PET/CT-positive patients receive 3 cycles of BEACOPPesc
followed by another 3 cycles of BEACOPPesc. Mid-treatment evaluation is
performed after 4 cycles. In case of treatment failure (less than PR), the
patient goes off protocol treatment.
2. A standard arm, where patients are treated with four cycles of BEACOPPesc
followed by 2 cycles of BEACOPPesc. Very early PET/CT is performed after one
cycle, but with no therapeutic consequences. Mid-treatment evaluation is
performed after four cycles. In case of treatment failure (less than PR), the
patient goes off protocol treatment.
Only patients with residual PET positive disease after chemotherapy will
receive radiotherapy (36 Gy/18 fractions to the FDG-PET/CT positive residual
mass (es).
Intervention
The standard arm is 6 cycli escBEACOPP
After cycle 1, after completion of chemotherapy and, if applicable after
completion of radiotherapy a FDG-PET/CT scan is being made.
The experimentel arm is 1 cycle ABVD, followed by a PET-scan.
If the PET-scan after cycle 1 is negative, another 5 cycli of ABVD will follow.
If the PET-scan after cylce 1 is positive, another 6 cycli of escBEACOPP will
follow.
After completion of chemotherapy and, if applicabele after completion of
radiotherapy an other FDG-PET/CT scan will be made.
Study burden and risks
Both the ABVD scheme as escBEACOPP scheme is being used in the daily
practice.Therefore it gives no extra risks.
FDG-PET/CT scan gives an extra radiation exposure.
From patients who participate in the side study extra blood will be taken
during regular control. Patients will not have to undergo an extra puncture.
Avenue Emanuel Mounier 83/11
Brussels 1200
BE
Avenue Emanuel Mounier 83/11
Brussels 1200
BE
Listed location countries
Age
Inclusion criteria
* Previously untreated, histologically proven classical Hodgkin lymphoma
* Clinical stages III/IV (Ann Arbor, see Appendix F)
* Age 18-60
* WHO performance 0-2 (see Appendix C)
* FDG-PET/CT scan prospectively planned after one cycle of chemotherapy in all patients
* Adequate organ function:;* Heart:
New York Heart Association (NYHA) functional classification <= II (EF >= 50% or FS >= 25%)
No symptomatic coronary heart disease (stable angina pectoris is allowed),
No severe uncontrolled hypertension.;* Liver: Total Bilirubin <= 2 x UNL, alanine aminotransferase (ALT, SGPT) <= 3 x UNL, aspartate aminotransferase (AST, SGOT) <= 3 x UNL (exception: elevated values due to HL liver involvement).;* Kidney: creatinine clearance >= 60 ml/min (measured or calculated according to the method of Cockcroft), uric acid, calcium (all <UNL).;* Hematological: Hemoglobin >= 10 g/dl, Leukocyte concentration >= 3.0 x 109/L absolute neutrophil count >= 1.5 x 109/L, platelets >= 75 x 109 /L. (exception: reduced values related to HL (e.g. BM infiltration, splenomegaly));Patients with a buffer range from the normal values of +/- 10% for hematology and +/- 10% for biochemistry are acceptable.;* Patients of childbearing/reproductive potential should use adequate birth control measures during the whole duration of study treatment.;* Female subjects of childbearing potential (defined as any female subject unless she meets at least one of the following criteria: Age >=50 years and naturally amenorrheic for >= 1 year {amenorrhea following cancer therapy does not rule out childbearing potential}, premature ovarian failure confirmed by a specialist gynecologist, previous bilateral salpingo-oophorectomy or hysterectomy, XY genotype, Turner syndrome or uterine agenesis.) must:;* Agree to have a medically supervised pregnancy test with a minimum sensitivity of 25 mIU/ml not more than 3 days before the start of study medication. This requirement also applies to women of childbearing potential who practice complete and continued abstinence;* Male subjects must:;* Agree to use condoms throughout study drug therapy, during any dose interruption and for one week after cessation of study therapy if their partner is of childbearing potential and has no contraception.;* Agree not to donate semen during study drug therapy and for one week after end of study drug therapy.;* Written informed consent according to ICH/EU Good Clinical Practice, and national/local regulations
Exclusion criteria
No pregnancy or breast feeding
* No specific contraindications to BEACOPPesc therapy, so therefore:
* poorly controlled diabetes mellitus
* known HIV infection
* chronic active hepatitis B and/or hepatitis C
* concomitant or previous malignancies with the exception of basal cell skin tumors, adequately treated carcinoma in situ of the cervix and any cancer that has been in complete remission for > 5 years
* No psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before randomization in the trial.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-005473-22-NL |
| CCMO | NL42634.042.12 |