Pediatric Hodgkin Lymphoma Treatment Trial With Low Cumulative Doses of Chemotherapy Agents and Reduced Radiation. (LHGALOP2017)
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| ClinicalTrials.gov Identifier: NCT03500133 |
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Recruitment Status :
Recruiting
First Posted : April 17, 2018
Last Update Posted : March 20, 2024
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Pediatric Hodgkin's Disease | 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. 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 Drug: Intermediate risk with complete early response after two cycles of ABVD chemotherapy schedule. Three more ABVD courses are delivered. Drug: Intermediate risk with partial remission after two cycles of ABVD chemotherapy schedule. 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. Drug: High risk with partial remission after 1 ABVD and 1 ESHAP courses. Six more chemotherapy courses are delivered alternating ESHAP and ABVD. Drug: Low risk with partial remission at early response assessment after two cycles of ABVD chemotherpay schedule. Two ABVD courses are delivered. | Phase 4 |
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 Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 500 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention 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) |
| Primary Purpose: | Treatment |
| 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. |
| Actual Study Start Date : | October 6, 2017 |
| Estimated Primary Completion Date : | October 31, 2027 |
| Estimated Study Completion Date : | October 31, 2032 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Group A
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. |
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. |
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Experimental: Group B
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 |
Radiation: No radiotherapy if CR at the end of chemotherapy.
Adapted chemotherapy without radiotherapy 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. |
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Experimental: Group B2
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 |
Radiation: No radiotherapy if CR at the end of chemotherapy.
Adapted chemotherapy without radiotherapy Drug: 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 |
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Experimental: Group C
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. |
Radiation: No radiotherapy if CR at the end of chemotherapy.
Adapted chemotherapy without radiotherapy 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. |
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Experimental: Group D
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 |
Radiation: No radiotherapy if CR at the end of chemotherapy.
Adapted chemotherapy without radiotherapy 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 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. |
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Experimental: Group E
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 |
Radiation: No radiotherapy if CR at the end of chemotherapy.
Adapted chemotherapy without radiotherapy 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. |
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Experimental: Group F
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 |
Radiation: No radiotherapy if CR at the end of chemotherapy.
Adapted chemotherapy without radiotherapy 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: 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. |
- 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)
- Acute, chronic or late toxic events [ Time Frame: 0-10 years ]Number of patientsexperiencing treatment-related adverse effects and mortality according to CTCAE v4.0
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| Ages Eligible for Study: | 2 Years to 18 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03500133
| Contact: Pedro A Zubizarreta, MD | +541131207433 | pedro.zubizarreta@hotmail.com | |
| Contact: Elizabeth M Alfaro, MD | +541159763263 | elizabeth2006_alfaro@yahoo.com.ar |
| Argentina | |
| Hospital JP Garrahan | Recruiting |
| Buenos Aires, CF, Argentina, C1245AAL | |
| Contact: Silvina Ruvinsky, MD 541156909663 coordinacioninvestigacion@garrahan.gov.ar | |
| Contact: Pedro A Zubizarreta, MD 541131207433 pedro.zubizarreta@hotmail.com | |
| Sub-Investigator: Elizabeth Alfaro, MD | |
| Sub-Investigator: Myriam Guitter, MD | |
| Sub-Investigator: Cristian Sanchez La Rosa, MD | |
| Sub-Investigator: María S Felice, MD | |
| Sub-Investigator: Magdalena Schelotto, MD | |
| Principal Investigator: Pedro A Zubizarreta, MD | |
| Sub-Investigator: Luisina Peruzzo, MD | |
| Sub-Investigator: Carla Pennella, MD | |
| Sub-Investigator: Carolina Romero, MD | |
| Responsible Party: | Pedro Zubizarreta, MD, Hospital JP Garrahan |
| ClinicalTrials.gov Identifier: | NCT03500133 |
| Other Study ID Numbers: |
991 Hodgkin Lymphoma GALOP2017 |
| First Posted: | April 17, 2018 Key Record Dates |
| Last Update Posted: | March 20, 2024 |
| Last Verified: | March 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Pediatric Hodgkin Lymphoma, therapy, reduced radiotherapy |
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Lymphoma Hodgkin Disease Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Cytarabine Methylprednisolone Cisplatin Etoposide Antineoplastic Agents Antimetabolites, Antineoplastic Antimetabolites |
Molecular Mechanisms of Pharmacological Action Antiviral Agents Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents, Phytogenic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Gastrointestinal Agents |