Pediatric Hodgkin's DiseasePhase 4LHGALOP2017NCT03500133
Pediatric Hodgkin Lymphoma Treatment Trial With Low Cumulative Doses of Chemotherapy Agents and Reduced Radiation.
A Phase 4 study testing No radiotherapy if CR at the end of chemotherapy., Low risk with complete early response after two cycles of ABVD chemotherapy schedule. Only one more ABVD course is delivered. and Low risk with partial remisssion after 4 cycles of ABVD chemotherapy schedule. Two ESHAP courses are delivered. in people with Pediatric Hodgkin's Disease, run by Hospital JP Garrahan at 1 site in Argentina.
Trial summary
This trial proposes a therapy for pediatric Hodgkin lymphoma with the objective of achieving high levels of long lasting complete remission with less risk of late effects. Patients of both genders, between 2 and 18 years, with newly diagnosed classical Hodgkin lymphoma are admitted. Read more about this study
- Who is it for?
- Ages 2 to 18 years
- Conditions the study is for
- Pediatric Hodgkin's Disease
- What is being tested?
- No radiotherapy if CR at the end of chemotherapy., Low risk with complete early response after two cycles of ABVD chemotherapy schedule. Only one more ABVD course is delivered. and Low risk with partial remisssion after 4 cycles of ABVD chemotherapy schedule. Two ESHAP courses are delivered.
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 500 participants
- Where
- 1 siteArgentina
- Study dates
- 6 Oct 2017to 31 Oct 2032
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Histopathological diagnosis of classical Hodgkin lymphoma.
- Normal renal, hepatic, pulmonary and metabolic function standards.
- Informed consent signed by patient and/or legal caretakers.
Who cannot join
- Lymphocyte predominant nodular Hodgkin lymphoma
- Any form of immunodeficiency before diagnosis. (primary immunodeficiencies, trasplant recipients or immunosuppressive therapies of any kind including corticoid therapies during 28 days before diagnosis).
- Pregnancy and breastfeeding period.
- Sexually active female patients who do not accept an effective contraceptive method during therapy.
- Positive HIV serology.
- Penfigus or hepatic ductopenia.
- Hodgkin lymphoma as a secondary malignant disease.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Argentina1 site, 1 recruiting
- Recruiting
Hospital JP Garrahan
Buenos Aires, Buenos Aires F.D., C1245AAL
Silvina Ruvinsky, MD, 541156909663, coordinacioninvestigacion@garrahan.gov.ar
Pedro A Zubizarreta, MD, 541131207433, pedro.zubizarreta@hotmail.com
About this study
Official title: Non Randomized, Multicenter, Prospective Pediatric Hodgkin Lymphoma Treatment Trial Stratified According to Initial Risk Factors and Response to Chemotherapy, Reduced Cumulative Doses of Antineoplastic Agents and Radiotherapy.
This trial proposes a therapy for pediatric Hodgkin lymphoma with the objective of achieving high levels of long lasting complete remission with less risk of late effects.
Patients of both genders, between 2 and 18 years, with newly diagnosed classical Hodgkin lymphoma are admitted.
Read more
Initial staging provides stratification in three groups: low, intermediate and high risk. An initial set of two chemotherapy courses is administered to all cases after which a new disease assessment is performed. According to disease response a final therapy group is assigned. Rapid early responders benefit from less chemotherapy. At the end of chemotherapy, radiotherapy is delivered only to patients who do not achieve a complete response. Thus therapy is tailored to initial extension and disease responsiveness. Complete responders at the end of chemotherapy do not receive radiotherapy. Those who are in partial remission receive low dose (30Gy) involved node radiotherapy. Stable or progressive disease at any moment is assumed as a trial failure and new therapeutic strategies are offered to patients off protocol.
Chemotherapy is based upon regimes with well known effectiveness in Hodgkin lymphoma. (i.e. ABVD: doxorubicin, bleomycin, vinblastine and dacarbazine and ESHAP: Etoposide, methyl prednisolone, citarabine and cisplatin). The schedules are delivered with low cumulative drug doses and avoiding the use of toxic alkylating agents. Risks of secondary leukemia and infertility are thus minimized. Doxorubicin and bleomycin do not achieve cumulative doses that may expose to significant risk of heart or lung damage. Radiotherapy reduction avoids late radiation sequels.
This clinical study proposes a therapeutic approach based on chemotherapy that do not sum up high cumulative toxic doses. Therapy is tailored according to initial risk assessment and disease responsiveness. Those who achieve a complete response to chemotherapy do not receive additional radiotherapy, thus avoiding further late effects.
Read the detailed description
This trial proposes a therapy for pediatric Hodgkin lymphoma with the objective of achieving high levels of long lasting complete remission with less risk of late effects.
Patients of both genders, between 2 and 18 years, with newly diagnosed classical Hodgkin lymphoma are admitted. An open surgical biopsy with histopatological diagnosis is preferred.
Initial staging provides stratification in three groups: low, intermediate and high risk. An initial set of two chemotherapy courses is administered to all cases after which an early disease response assessment is performed. According to disease response a final therapy group is assigned (7 arms).
Imaging with PET-CT and Deauville Score is preferred for initial and further disease assessment. Complete response is defined by volume reduction and metabolic remission. In case PET-CT is not available, CT and ultrasound with volume reduction standards to assess response may be used.
Rapid early responders who achieve complete remission (CR) benefit from less chemotherapy. Those who are in partial remission at the end of chemotherapy (late disease assessment) receive low dose (30Gy) involved node radiotherapy. At the end of chemotherapy, radiotherapy is delivered only to patients who do not achieve a CR. Thus, therapy is tailored according to initial extension and disease responsiveness. Complete responders at the end of chemotherapy do not receive radiotherapy. To avoid radiotherapy in the majority of cases constitutes a principal goal of this trial. Stable or progressive disease at any moment is assumed as a trial failure and new therapeutic strategies are offered to these patients off protocol.
Chemotherapy is based upon regimes with well known effectiveness in Hodgkin lymphoma. (i.e. ABVD: doxorubicin, bleomycin, vinblastine and dacarbazine and ESHAP: Etoposide, methyl prednisolone, citarabine and cisplatin).
Low risk arms (Arms A, B and B2) receive no more than 4 cycles of ABVD. Intermediate risk Arm C, 5 cycles of ABVD and Arm D 4 cycles of ABVD and 2 courses of ESHAP. High risk Arm E receives 3 cycles of ABVD and 3 Cycles of ESHAP, Arm F receives 4 courses of ABVD and 4 courses of ESHAP. The schedules are delivered projecting low cumulative drug doses and avoiding the use of toxic alkylating agents. Risks of secondary leukemia and infertility are thus minimized. Doxorubicin and bleomycin do not achieve cumulative doses that may expose to significant risk of heart or lung damage. Radiotherapy reduction avoids late radiation sequels.
Cardiac, lung , thyroid and any other toxic effects are prospectively assessed at onset and regularly during and after therapy.
The main event-free and overall survival proportions end points will be analyzed annually during the following 10 years after the last patient registration.
This clinical study proposes a therapeutic approach based on chemotherapy that do not sum up high cumulative toxic doses. Therapy is tailored according to initial risk assessment and disease responsiveness. Those who achieve a complete response after chemotherapy do not receive additional radiotherapy, thus avoiding further late effects.
- Conditions
- Pediatric Hodgkin's Disease
- Being tested
- No radiotherapy if CR at the end of chemotherapy., Low risk with complete early response after two cycles of ABVD chemotherapy schedule. Only one more ABVD course is delivered., Low risk with partial remisssion after 4 cycles of ABVD chemotherapy schedule. Two ESHAP courses are delivered., IN 30Gy RT in case of PR at the end of chemotherapy, Intermediate risk with complete early response after two cycles of ABVD chemotherapy schedule. Three more ABVD courses are delivered.
- Keywords
- Pediatric Hodgkin Lymphoma, therapy, reduced radiotherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No radiotherapy if CR at the end of chemotherapy.Radiation
Adapted chemotherapy without radiotherapy
Low risk with complete early response after two cycles of ABVD chemotherapy schedule. Only one more ABVD course is delivered.Drug
Low risk with complete early response after two cycles of ABVD chemotherapy schedule. Only one more ABVD course is delivered.
Low risk with partial remisssion after 4 cycles of ABVD chemotherapy schedule. Two ESHAP courses are delivered.Drug
Low risk with partial remission at early response assessment after two cycles of ABVD chemotherpay schedule. Two ABVD courses are delivered.
IN 30Gy RT in case of PR at the end of chemotherapyRadiation
Low risk with partial remisssion after 4 cycles of ABVD and 2 ESHAP courses: IN 30Gy RT
Intermediate risk with complete early response after two cycles of ABVD chemotherapy schedule. Three more ABVD courses are delivered.Drug
Intermediate risk with complete early response after two cycles of ABVD chemotherapy schedule. Three more ABVD courses are delivered.
Intermediate risk with partial remission after two cycles of ABVD chemotherapy schedule. Four more chemotherapy courses are delivered alternating ESHAP and ABVD.Drug
Intermediate risk with partial remission after two cycles of ABVD chemotherapy schedule. Four more chemotherapy courses are delivered alternating ESHAP and ABVD.
High risk with complete early response after 1 ABVD and 1 ESHAP courses. Four more chemotherapy courses are delivered alternating ESHAP and ABVD.Drug
High risk with complete early response after 1 ABVD and 1 ESHAP courses. Four more chemotherapy courses are delivered alternating ESHAP and ABVD.
High risk with partial remission after 1 ABVD and 1 ESHAP courses. Six more chemotherapy courses are delivered alternating ESHAP and ABVD.Drug
High risk with partial remission after 1 ABVD and 1 ESHAP courses. Six more chemotherapy courses are delivered alternating ESHAP and ABVD.
Low risk with partial remission at early response assessment after two cycles of ABVD chemotherpay schedule. Two ABVD courses are delivered.Drug
Low risk with partial remission at early response assessment after two cycles of ABVD chemotherpay schedule. Two ABVD courses are delivered.
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | Low risk with complete early response after two cycles of ABVD chemotherapy schedule. Only one more ABVD course is delivered.
No radiotherapy if CR at the end of chemotherapy. Receives: Radiation: No radiotherapy if CR at the end of chemotherapy.; Drug: Low risk with complete early response after two cycles of ABVD chemotherapy schedule. Only one more ABVD course is delivered. |
| Group B | Experimental | Low risk with partial remission at early response assessment after two cycles of ABVD chemotherpay schedule. Two ABVD courses are delivered.
No radiotherapy if CR at the end of chemotherapy Receives: Radiation: No radiotherapy if CR at the end of chemotherapy.; Drug: Low risk with partial remission at early response assessment after two cycles of ABVD chemotherpay schedule. Two ABVD courses are delivered. |
| Group B2 | Experimental | Low risk with partial remisssion after 4 cycles of ABVD chemotherapy schedule. Two ESHAP courses are delivered.
No radiotherapy if CR at the end of chemotherapy. IN 30Gy RT in case of PR at the end of chemotherapy Receives: Radiation: No radiotherapy if CR at the end of chemotherapy.; Drug: Low risk with partial remisssion after 4 cycles of ABVD chemotherapy schedule. Two ESHAP courses are delivered.; Radiation: IN 30Gy RT in case of PR at the end of chemotherapy |
| Group C | Experimental | Intermediate risk with complete early response after two cycles of ABVD chemotherapy schedule. Three more ABVD courses are delivered.
No radiotherapy if CR at the end of chemotherapy. Receives: Radiation: No radiotherapy if CR at the end of chemotherapy.; Drug: Intermediate risk with complete early response after two cycles of ABVD chemotherapy schedule. Three more ABVD courses are delivered. |
| Group D | Experimental | Intermediate risk with partial remission after two cycles of ABVD chemotherapy schedule. Four more chemotherapy courses are delivered alternating ESHAP and ABVD.
No radiotherapy if CR at the end of chemotherapy. IN 30Gy RT in case of PR at the end of chemotherapy Receives: Radiation: No radiotherapy if CR at the end of chemotherapy.; Radiation: IN 30Gy RT in case of PR at the end of chemotherapy; Drug: Intermediate risk with partial remission after two cycles of ABVD chemotherapy schedule. Four more chemotherapy courses are delivered alternating ESHAP and ABVD. |
| Group E | Experimental | High risk with complete early response after 1 ABVD and 1 ESHAP courses. Four more chemotherapy courses are delivered alternating ESHAP and ABVD.
No radiotherapy if CR at the end of chemotherapy Receives: Radiation: No radiotherapy if CR at the end of chemotherapy.; Drug: High risk with complete early response after 1 ABVD and 1 ESHAP courses. Four more chemotherapy courses are delivered alternating ESHAP and ABVD. |
| Group F | Experimental | High risk with partial remission after 1 ABVD and 1 ESHAP courses. Six more chemotherapy courses are delivered alternating ESHAP and ABVD.
No radiotherapy if CR at the end of chemotherapy. IN 30Gy RT in case of PR at the end of chemotherapy Receives: Radiation: No radiotherapy if CR at the end of chemotherapy.; Radiation: IN 30Gy RT in case of PR at the end of chemotherapy; Drug: High risk with partial remission after 1 ABVD and 1 ESHAP courses. Six more chemotherapy courses are delivered alternating ESHAP and ABVD. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free Survival
Event free survival probability (event= relapse or death)
Measured: 3-10 years
Overall Survival
Overall survival probability (event= death)
Measured: 3-10 years
Secondary outcomes (1)
Acute, chronic or late toxic events
Number of patientsexperiencing treatment-related adverse effects and mortality according to CTCAE v4.0
Measured: 0-10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2018
- Study start6 Oct 2017
- Primary completion31 Oct 2027 (estimated)
- Study completion31 Oct 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for Pediatric Hodgkin's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Initial disease risk assignment defines three arms: low, intermediate and high risk. After early disease response assessment 7 Arms are defined, treated with more intense chemotherapy according to initial risk and therapy response. Finally radiotherapy is delivered only to patients who do not achieve complete remission after chemotherapy at late disease response assessment.
- Masking
- None (open label)
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital JP Garrahan
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Pedro Zubizarreta, Hospital JP Garrahan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03500133
- Sponsor's protocol ID
- 991 Hodgkin Lymphoma GALOP2017
- Acronym
- LHGALOP2017
- Status last verified
- Apr 2025
- First submitted
- 9 Apr 2018
- Last updated
- 16 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Driscoll JJ, Rixe O. Overall survival: still the gold standard: why overall survival remains the definitive end point in cancer clinical trials. Cancer J. 2009 Sep-Oct;15(5):401-5. doi: 10.1097/PPO.0b013e3181bdc2e0.
PubMed 19826360Ellis LM, Bernstein DS, Voest EE, Berlin JD, Sargent D, Cortazar P, Garrett-Mayer E, Herbst RS, Lilenbaum RC, Sima C, Venook AP, Gonen M, Schilsky RL, Meropol NJ, Schnipper LE. American Society of Clinical Oncology perspective: Raising the bar for clinical trials by defining clinically meaningful outcomes. J Clin Oncol. 2014 Apr 20;32(12):1277-80. doi: 10.1200/JCO.2013.53.8009. Epub 2014 Mar 17. No abstract available.
PubMed 24638016Nachman JB, Sposto R, Herzog P, Gilchrist GS, Wolden SL, Thomson J, Kadin ME, Pattengale P, Davis PC, Hutchinson RJ, White K; Children's Cancer Group. Randomized comparison of low-dose involved-field radiotherapy and no radiotherapy for children with Hodgkin's disease who achieve a complete response to chemotherapy. J Clin Oncol. 2002 Sep 15;20(18):3765-71. doi: 10.1200/JCO.2002.12.007.
PubMed 12228196Wolden SL, Chen L, Kelly KM, Herzog P, Gilchrist GS, Thomson J, Sposto R, Kadin ME, Hutchinson RJ, Nachman J. Long-term results of CCG 5942: a randomized comparison of chemotherapy with and without radiotherapy for children with Hodgkin's lymphoma--a report from the Children's Oncology Group. J Clin Oncol. 2012 Sep 10;30(26):3174-80. doi: 10.1200/JCO.2011.41.1819. Epub 2012 May 29.
PubMed 22649136Dorffel W, Ruhl U, Luders H, Claviez A, Albrecht M, Bokkerink J, Holte H, Karlen J, Mann G, Marciniak H, Niggli F, Schmiegelow K, Schwarze EW, Potter R, Wickmann L, Schellong G. Treatment of children and adolescents with Hodgkin lymphoma without radiotherapy for patients in complete remission after chemotherapy: final results of the multinational trial GPOH-HD95. J Clin Oncol. 2013 Apr 20;31(12):1562-8. doi: 10.1200/JCO.2012.45.3266. Epub 2013 Mar 18.
PubMed 23509321Sackmann-Muriel F, Zubizarreta P, Gallo G, Scopinaro M, Alderete D, Alfaro E, Casak S, Chantada G, Felice MS, Quinteros R. Hodgkin disease in children: results of a prospective randomized trial in a single institution in Argentina. Med Pediatr Oncol. 1997 Dec;29(6):544-52. doi: 10.1002/(sici)1096-911x(199712)29:63.0.co;2-k.
PubMed 9324342Kelly KM, Sposto R, Hutchinson R, Massey V, McCarten K, Perkins S, Lones M, Villaluna D, Weiner M. BEACOPP chemotherapy is a highly effective regimen in children and adolescents with high-risk Hodgkin lymphoma: a report from the Children's Oncology Group. Blood. 2011 Mar 3;117(9):2596-603. doi: 10.1182/blood-2010-05-285379. Epub 2010 Nov 15.
PubMed 21079154Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, Lipshultz SE, Turner CS, deAlarcon PA, Chauvenet A. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009 Sep 3;114(10):2051-9. doi: 10.1182/blood-2008-10-184143. Epub 2009 Jul 7.
PubMed 19584400Mauz-Korholz C, Hasenclever D, Dorffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlen J, Bergstrasser E, Fossa A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Korholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. doi: 10.1200/JCO.2009.26.9381. Epub 2010 Jul 12.
PubMed 20625128Zubizarreta PA, Alfaro E, Guitter M, Sanchez La Rosa C, Galluzzo ML, Millan N, Fiandrino F, Felice MS. Children and Adolescent Hodgkin Lymphoma in Argentina: Long-term Results After Combined ABVD and Restricted Radiotherapy. J Pediatr Hematol Oncol. 2017 Nov;39(8):602-608. doi: 10.1097/MPH.0000000000000943.
PubMed 28902084Mauz-Korholz C, Metzger ML, Kelly KM, Schwartz CL, Castellanos ME, Dieckmann K, Kluge R, Korholz D. Pediatric Hodgkin Lymphoma. J Clin Oncol. 2015 Sep 20;33(27):2975-85. doi: 10.1200/JCO.2014.59.4853. Epub 2015 Aug 24.
PubMed 26304892Johnson P, Federico M, Kirkwood A, Fossa A, Berkahn L, Carella A, d'Amore F, Enblad G, Franceschetto A, Fulham M, Luminari S, O'Doherty M, Patrick P, Roberts T, Sidra G, Stevens L, Smith P, Trotman J, Viney Z, Radford J, Barrington S. Adapted Treatment Guided by Interim PET-CT Scan in Advanced Hodgkin's Lymphoma. N Engl J Med. 2016 Jun 23;374(25):2419-29. doi: 10.1056/NEJMoa1510093.
PubMed 27332902Velasquez WS, McLaughlin P, Tucker S, Hagemeister FB, Swan F, Rodriguez MA, Romaguera J, Rubenstein E, Cabanillas F. ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol. 1994 Jun;12(6):1169-76. doi: 10.1200/JCO.1994.12.6.1169.
PubMed 8201379Labrador J, Cabrero-Calvo M, Perez-Lopez E, Mateos MV, Vazquez L, Caballero MD, Garcia-Sanz R. ESHAP as salvage therapy for relapsed or refractory Hodgkin's lymphoma. Ann Hematol. 2014 Oct;93(10):1745-53. doi: 10.1007/s00277-014-2114-0. Epub 2014 May 27.
PubMed 24863692Furth C, Amthauer H, Hautzel H, Steffen IG, Ruf J, Schiefer J, Schonberger S, Henze G, Grandt R, Hundsdoerfer P, Dietlein M, Kobe C. Evaluation of interim PET response criteria in paediatric Hodgkin's lymphoma--results for dedicated assessment criteria in a blinded dual-centre read. Ann Oncol. 2011 May;22(5):1198-1203. doi: 10.1093/annonc/mdq557. Epub 2010 Oct 21.
PubMed 20966182
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non Randomized, Multicenter, Prospective Pediatric Hodgkin Lymphoma Treatment Trial Stratified According to Initial Risk Factors and Response to Chemotherapy, Reduced Cumulative Doses of Antineoplastic Agents and Radiotherapy.
- ClinicalTrials.gov ID
- NCT03500133
- Acronym / sponsor ID
- LHGALOP2017 / 991 Hodgkin Lymphoma GALOP2017
- Conditions
- Pediatric Hodgkin's Disease
- Keywords
- Pediatric Hodgkin Lymphoma, therapy, reduced radiotherapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Hospital JP GarrahanOther government
- Study start
- 6 Oct 2017 (actual)
- Primary completion
- 31 Oct 2027 (estimated)
- Study completion
- 31 Oct 2032 (estimated)
- First posted
- 17 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial proposes a therapy for pediatric Hodgkin lymphoma with the objective of achieving high levels of long lasting complete remission with less risk of late effects.
Patients of both genders, between 2 and 18 years, with newly diagnosed classical Hodgkin lymphoma are admitted.
Initial staging provides stratification in three groups: low, intermediate and high risk. An initial set of two chemotherapy courses is administered to all cases after which a new disease assessment is performed. According to disease response a final therapy group is assigned. Rapid early responders benefit from less chemotherapy. At the end of chemotherapy, radiotherapy is delivered only to patients who do not achieve a complete response. Thus therapy is tailored to initial extension and disease responsiveness. Complete responders at the end of chemotherapy do not receive radiotherapy. Those who are in partial remission receive low dose (30Gy) involved node radiotherapy. Stable or progressive disease at any moment is assumed as a trial failure and new therapeutic strategies are offered to patients off protocol.
Chemotherapy is based upon regimes with well known effectiveness in Hodgkin lymphoma. (i.e. ABVD: doxorubicin, bleomycin, vinblastine and dacarbazine and ESHAP: Etoposide, methyl prednisolone, citarabine and cisplatin). The schedules are delivered with low cumulative drug doses and avoiding the use of toxic alkylating agents. Risks of secondary leukemia and infertility are thus minimized. Doxorubicin and bleomycin do not achieve cumulative doses that may expose to significant risk of heart or lung damage. Radiotherapy reduction avoids late radiation sequels.
This clinical study proposes a therapeutic approach based on chemotherapy that do not sum up high cumulative toxic doses. Therapy is tailored according to initial risk assessment and disease responsiveness. Those who achieve a complete response to chemotherapy do not receive additional radiotherapy, thus avoiding further late effects.
Detailed description
This trial proposes a therapy for pediatric Hodgkin lymphoma with the objective of achieving high levels of long lasting complete remission with less risk of late effects.
Patients of both genders, between 2 and 18 years, with newly diagnosed classical Hodgkin lymphoma are admitted. An open surgical biopsy with histopatological diagnosis is preferred.
Initial staging provides stratification in three groups: low, intermediate and high risk. An initial set of two chemotherapy courses is administered to all cases after which an early disease response assessment is performed. According to disease response a final therapy group is assigned (7 arms).
Imaging with PET-CT and Deauville Score is preferred for initial and further disease assessment. Complete response is defined by volume reduction and metabolic remission. In case PET-CT is not available, CT and ultrasound with volume reduction standards to assess response may be used.
Rapid early responders who achieve complete remission (CR) benefit from less chemotherapy. Those who are in partial remission at the end of chemotherapy (late disease assessment) receive low dose (30Gy) involved node radiotherapy. At the end of chemotherapy, radiotherapy is delivered only to patients who do not achieve a CR. Thus, therapy is tailored according to initial extension and disease responsiveness. Complete responders at the end of chemotherapy do not receive radiotherapy. To avoid radiotherapy in the majority of cases constitutes a principal goal of this trial. Stable or progressive disease at any moment is assumed as a trial failure and new therapeutic strategies are offered to these patients off protocol.
Chemotherapy is based upon regimes with well known effectiveness in Hodgkin lymphoma. (i.e. ABVD: doxorubicin, bleomycin, vinblastine and dacarbazine and ESHAP: Etoposide, methyl prednisolone, citarabine and cisplatin).
Low risk arms (Arms A, B and B2) receive no more than 4 cycles of ABVD. Intermediate risk Arm C, 5 cycles of ABVD and Arm D 4 cycles of ABVD and 2 courses of ESHAP. High risk Arm E receives 3 cycles of ABVD and 3 Cycles of ESHAP, Arm F receives 4 courses of ABVD and 4 courses of ESHAP. The schedules are delivered projecting low cumulative drug doses and avoiding the use of toxic alkylating agents. Risks of secondary leukemia and infertility are thus minimized. Doxorubicin and bleomycin do not achieve cumulative doses that may expose to significant risk of heart or lung damage. Radiotherapy reduction avoids late radiation sequels.
Cardiac, lung , thyroid and any other toxic effects are prospectively assessed at onset and regularly during and after therapy.
The main event-free and overall survival proportions end points will be analyzed annually during the following 10 years after the last patient registration.
This clinical study proposes a therapeutic approach based on chemotherapy that do not sum up high cumulative toxic doses. Therapy is tailored according to initial risk assessment and disease responsiveness. Those who achieve a complete response after chemotherapy do not receive additional radiotherapy, thus avoiding further late effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
- Model description
- Initial disease risk assignment defines three arms: low, intermediate and high risk. After early disease response assessment 7 Arms are defined, treated with more intense chemotherapy according to initial risk and therapy response. Finally radiotherapy is delivered only to patients who do not achieve complete remission after chemotherapy at late disease response assessment.
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Radiation: No radiotherapy if CR at the end of chemotherapy., Drug: Low risk with complete early response after two cycles of ABVD chemotherapy schedule. Only one more ABVD course is delivered.Low risk with complete early response after two cycles of ABVD chemotherapy schedule. Only one more ABVD course is delivered. No radiotherapy if CR at the end of chemotherapy. |
| Group B | Experimental | Radiation: No radiotherapy if CR at the end of chemotherapy., Drug: Low risk with partial remission at early response assessment after two cycles of ABVD chemotherpay schedule. Two ABVD courses are delivered.Low risk with partial remission at early response assessment after two cycles of ABVD chemotherpay schedule. Two ABVD courses are delivered. No radiotherapy if CR at the end of chemotherapy |
| Group B2 | Experimental | Radiation: No radiotherapy if CR at the end of chemotherapy., Drug: Low risk with partial remisssion after 4 cycles of ABVD chemotherapy schedule. Two ESHAP courses are delivered., Radiation: IN 30Gy RT in case of PR at the end of chemotherapyLow risk with partial remisssion after 4 cycles of ABVD chemotherapy schedule. Two ESHAP courses are delivered. No radiotherapy if CR at the end of chemotherapy. IN 30Gy RT in case of PR at the end of chemotherapy |
| Group C | Experimental | Radiation: No radiotherapy if CR at the end of chemotherapy., Drug: Intermediate risk with complete early response after two cycles of ABVD chemotherapy schedule. Three more ABVD courses are delivered.Intermediate risk with complete early response after two cycles of ABVD chemotherapy schedule. Three more ABVD courses are delivered. No radiotherapy if CR at the end of chemotherapy. |
| Group D | Experimental | Radiation: No radiotherapy if CR at the end of chemotherapy., Radiation: IN 30Gy RT in case of PR at the end of chemotherapy, Drug: Intermediate risk with partial remission after two cycles of ABVD chemotherapy schedule. Four more chemotherapy courses are delivered alternating ESHAP and ABVD.Intermediate risk with partial remission after two cycles of ABVD chemotherapy schedule. Four more chemotherapy courses are delivered alternating ESHAP and ABVD. No radiotherapy if CR at the end of chemotherapy. IN 30Gy RT in case of PR at the end of chemotherapy |
| Group E | Experimental | Radiation: No radiotherapy if CR at the end of chemotherapy., Drug: High risk with complete early response after 1 ABVD and 1 ESHAP courses. Four more chemotherapy courses are delivered alternating ESHAP and ABVD.High risk with complete early response after 1 ABVD and 1 ESHAP courses. Four more chemotherapy courses are delivered alternating ESHAP and ABVD. No radiotherapy if CR at the end of chemotherapy |
| Group F | Experimental | Radiation: No radiotherapy if CR at the end of chemotherapy., Radiation: IN 30Gy RT in case of PR at the end of chemotherapy, Drug: High risk with partial remission after 1 ABVD and 1 ESHAP courses. Six more chemotherapy courses are delivered alternating ESHAP and ABVD.High risk with partial remission after 1 ABVD and 1 ESHAP courses. Six more chemotherapy courses are delivered alternating ESHAP and ABVD. No radiotherapy if CR at the end of chemotherapy. IN 30Gy RT in case of PR at the end of chemotherapy |
Who may qualify
- Ages
- 2 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Histopathological diagnosis of classical Hodgkin lymphoma.
- Normal renal, hepatic, pulmonary and metabolic function standards.
- Informed consent signed by patient and/or legal caretakers.
Key exclusion criteria (7 listed)
- Lymphocyte predominant nodular Hodgkin lymphoma
- Any form of immunodeficiency before diagnosis. (primary immunodeficiencies, trasplant recipients or immunosuppressive therapies of any kind including corticoid therapies during 28 days before diagnosis).
- Pregnancy and breastfeeding period.
- Sexually active female patients who do not accept an effective contraceptive method during therapy.
- Positive HIV serology.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| No radiotherapy if CR at the end of chemotherapy.Adapted chemotherapy without radiotherapy | Radiation | Group A, Group B, Group B2, Group C, Group D, Group E, Group F |
| Low risk with complete early response after two cycles of ABVD chemotherapy schedule. Only one more ABVD course is delivered.Low risk with complete early response after two cycles of ABVD chemotherapy schedule. Only one more ABVD course is delivered. | Drug | Group A |
| Low risk with partial remisssion after 4 cycles of ABVD chemotherapy schedule. Two ESHAP courses are delivered.Low risk with partial remission at early response assessment after two cycles of ABVD chemotherpay schedule. Two ABVD courses are delivered. | Drug | Group B2 |
| IN 30Gy RT in case of PR at the end of chemotherapyLow risk with partial remisssion after 4 cycles of ABVD and 2 ESHAP courses: IN 30Gy RT | Radiation | Group B2, Group D, Group F |
| Intermediate risk with complete early response after two cycles of ABVD chemotherapy schedule. Three more ABVD courses are delivered.Intermediate risk with complete early response after two cycles of ABVD chemotherapy schedule. Three more ABVD courses are delivered. | Drug | Group C |
| Intermediate risk with partial remission after two cycles of ABVD chemotherapy schedule. Four more chemotherapy courses are delivered alternating ESHAP and ABVD.Intermediate risk with partial remission after two cycles of ABVD chemotherapy schedule. Four more chemotherapy courses are delivered alternating ESHAP and ABVD. | Drug | Group D |
| High risk with complete early response after 1 ABVD and 1 ESHAP courses. Four more chemotherapy courses are delivered alternating ESHAP and ABVD.High risk with complete early response after 1 ABVD and 1 ESHAP courses. Four more chemotherapy courses are delivered alternating ESHAP and ABVD. | Drug | Group E |
| High risk with partial remission after 1 ABVD and 1 ESHAP courses. Six more chemotherapy courses are delivered alternating ESHAP and ABVD.High risk with partial remission after 1 ABVD and 1 ESHAP courses. Six more chemotherapy courses are delivered alternating ESHAP and ABVD. | Drug | Group F |
| Low risk with partial remission at early response assessment after two cycles of ABVD chemotherpay schedule. Two ABVD courses are delivered.Low risk with partial remission at early response assessment after two cycles of ABVD chemotherpay schedule. Two ABVD courses are delivered. | Drug | Group B |
Primary outcome
Event-free Survival
Time frame: 3-10 years
Event free survival probability (event= relapse or death)
Overall Survival
Time frame: 3-10 years
Overall survival probability (event= death)
1 secondary outcome
Acute, chronic or late toxic events
Time frame: 0-10 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2025.
- Background: PubMed 19826360Driscoll JJ, Rixe O. Overall survival: still the gold standard: why overall survival remains the definitive end point in cancer clinical trials. Cancer J. 2009 Sep-Oct;15(5):401-5. doi: 10.1097/PPO.0b013e3181bdc2e0.
- Background: PubMed 24638016Ellis LM, Bernstein DS, Voest EE, Berlin JD, Sargent D, Cortazar P, Garrett-Mayer E, Herbst RS, Lilenbaum RC, Sima C, Venook AP, Gonen M, Schilsky RL, Meropol NJ, Schnipper LE. American Society of Clinical Oncology perspective: Raising the bar for clinical trials by defining clinically meaningful outcomes. J Clin Oncol. 2014 Apr 20;32(12):1277-80. doi: 10.1200/JCO.2013.53.8009. Epub 2014 Mar 17. No abstract available.
- Background: PubMed 12228196Nachman JB, Sposto R, Herzog P, Gilchrist GS, Wolden SL, Thomson J, Kadin ME, Pattengale P, Davis PC, Hutchinson RJ, White K; Children's Cancer Group. Randomized comparison of low-dose involved-field radiotherapy and no radiotherapy for children with Hodgkin's disease who achieve a complete response to chemotherapy. J Clin Oncol. 2002 Sep 15;20(18):3765-71. doi: 10.1200/JCO.2002.12.007.
- Background: PubMed 22649136Wolden SL, Chen L, Kelly KM, Herzog P, Gilchrist GS, Thomson J, Sposto R, Kadin ME, Hutchinson RJ, Nachman J. Long-term results of CCG 5942: a randomized comparison of chemotherapy with and without radiotherapy for children with Hodgkin's lymphoma--a report from the Children's Oncology Group. J Clin Oncol. 2012 Sep 10;30(26):3174-80. doi: 10.1200/JCO.2011.41.1819. Epub 2012 May 29.
- Background: PubMed 23509321Dorffel W, Ruhl U, Luders H, Claviez A, Albrecht M, Bokkerink J, Holte H, Karlen J, Mann G, Marciniak H, Niggli F, Schmiegelow K, Schwarze EW, Potter R, Wickmann L, Schellong G. Treatment of children and adolescents with Hodgkin lymphoma without radiotherapy for patients in complete remission after chemotherapy: final results of the multinational trial GPOH-HD95. J Clin Oncol. 2013 Apr 20;31(12):1562-8. doi: 10.1200/JCO.2012.45.3266. Epub 2013 Mar 18.
- Background: PubMed 9324342Sackmann-Muriel F, Zubizarreta P, Gallo G, Scopinaro M, Alderete D, Alfaro E, Casak S, Chantada G, Felice MS, Quinteros R. Hodgkin disease in children: results of a prospective randomized trial in a single institution in Argentina. Med Pediatr Oncol. 1997 Dec;29(6):544-52. doi: 10.1002/(sici)1096-911x(199712)29:63.0.co;2-k.
- Background: PubMed 21079154Kelly KM, Sposto R, Hutchinson R, Massey V, McCarten K, Perkins S, Lones M, Villaluna D, Weiner M. BEACOPP chemotherapy is a highly effective regimen in children and adolescents with high-risk Hodgkin lymphoma: a report from the Children's Oncology Group. Blood. 2011 Mar 3;117(9):2596-603. doi: 10.1182/blood-2010-05-285379. Epub 2010 Nov 15.
- Background: PubMed 19584400Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, Lipshultz SE, Turner CS, deAlarcon PA, Chauvenet A. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009 Sep 3;114(10):2051-9. doi: 10.1182/blood-2008-10-184143. Epub 2009 Jul 7.
- Background: PubMed 20625128Mauz-Korholz C, Hasenclever D, Dorffel W, Ruschke K, Pelz T, Voigt A, Stiefel M, Winkler M, Vilser C, Dieckmann K, Karlen J, Bergstrasser E, Fossa A, Mann G, Hummel M, Klapper W, Stein H, Vordermark D, Kluge R, Korholz D. Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study. J Clin Oncol. 2010 Aug 10;28(23):3680-6. doi: 10.1200/JCO.2009.26.9381. Epub 2010 Jul 12.
- Background: PubMed 28902084Zubizarreta PA, Alfaro E, Guitter M, Sanchez La Rosa C, Galluzzo ML, Millan N, Fiandrino F, Felice MS. Children and Adolescent Hodgkin Lymphoma in Argentina: Long-term Results After Combined ABVD and Restricted Radiotherapy. J Pediatr Hematol Oncol. 2017 Nov;39(8):602-608. doi: 10.1097/MPH.0000000000000943.
- Background: PubMed 26304892Mauz-Korholz C, Metzger ML, Kelly KM, Schwartz CL, Castellanos ME, Dieckmann K, Kluge R, Korholz D. Pediatric Hodgkin Lymphoma. J Clin Oncol. 2015 Sep 20;33(27):2975-85. doi: 10.1200/JCO.2014.59.4853. Epub 2015 Aug 24.
- Background: PubMed 27332902Johnson P, Federico M, Kirkwood A, Fossa A, Berkahn L, Carella A, d'Amore F, Enblad G, Franceschetto A, Fulham M, Luminari S, O'Doherty M, Patrick P, Roberts T, Sidra G, Stevens L, Smith P, Trotman J, Viney Z, Radford J, Barrington S. Adapted Treatment Guided by Interim PET-CT Scan in Advanced Hodgkin's Lymphoma. N Engl J Med. 2016 Jun 23;374(25):2419-29. doi: 10.1056/NEJMoa1510093.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing No radiotherapy if CR at the end of chemotherapy., Low risk with complete early response after two cycles of ABVD chemotherapy schedule. Only one more ABVD course is delivered. and Low risk with partial remisssion after 4 cycles of ABVD chemotherapy schedule. Two ESHAP courses are delivered. in people with Pediatric Hodgkin's Disease, run by Hospital JP Garrahan at 1 site in Argentina.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Argentina. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Pedro A Zubizarreta, MD (+541131207433, pedro.zubizarreta@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event-free Survival (time frame: 3-10 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03500133, which also lists 22 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2025.