Pediatric Hodgkin Lymphoma Treatment Trial With Low Cumulative Doses of Chemotherapy Agents and Reduced Radiation.

Pediatric Hodgkin's Disease Clinical Trial

— LHGALOP2017  

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03500133
• Other study ID #: 991 Hodgkin Lymphoma GALOP2017
• Status: Recruiting
• Phase: Phase 4
• Start date: October 6, 2017
• Est. completion date: October 31, 2032

Study information

• Verified date: March 2024
• Source: Hospital JP Garrahan
• Contact: Pedro A Zubizarreta, MD
• Phone: +541131207433
• Email: pedro.zubizarreta[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: October 31, 2032
• Est. primary completion date: October 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 18 Years

Eligibility

Inclusion Criteria:

• Histopathological diagnosis of classical Hodgkin lymphoma.
• Normal renal, hepatic, pulmonary and metabolic function standards.
• Informed consent signed by patient and/or legal caretakers.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Hodgkin Disease
• Lymphoma
• Pediatric Hodgkin's Disease

Intervention

Radiation:
• No radiotherapy if CR at the end of chemotherapy.
Adapted chemotherapy without radiotherapy

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.
• 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.

Radiation:
• IN 30Gy RT in case of PR at the end of chemotherapy
Low risk with partial remisssion after 4 cycles of ABVD and 2 ESHAP courses: IN 30Gy RT

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.
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
Argentina	Hospital JP Garrahan	Buenos Aires	CF

Sponsors (2)

Lead Sponsor	Collaborator
Hospital JP Garrahan	Hospital Pereyra Rosell, Montevideo, Uruguay

Country where clinical trial is conducted

Argentina, 

References & Publications (22)

Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organisation for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Espanol de Medula Osea; German High-Grade Lymphoma Study Group; German Hodgkin's Study Group; Japanese Lymphorra Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68. doi: 10.1200/JCO.2013.54.8800. — View Citation

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Labrador 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. — View Citation

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Meignan M, Gallamini A, Itti E, Barrington S, Haioun C, Polliack A. Report on the Third International Workshop on Interim Positron Emission Tomography in Lymphoma held in Menton, France, 26-27 September 2011 and Menton 2011 consensus. Leuk Lymphoma. 2012 Oct;53(10):1876-81. doi: 10.3109/10428194.2012.677535. Epub 2012 Apr 23. — View Citation

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Sackmann-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. — View Citation

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Velasquez 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. — View Citation

Wolden 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. — View Citation

Zubizarreta 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. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free Survival	Event free survival probability (event= relapse or death)	3-10 years
Primary	Overall Survival	Overall survival probability (event= death)	3-10 years
Secondary	Acute, chronic or late toxic events	Number of patientsexperiencing treatment-related adverse effects and mortality according to CTCAE v4.0	0-10 years