Adcetris (Brentuximab Vedotin), Combination Chemotherapy, and Radiation Therapy in Treating Younger Patients With Stage IIB, IIIB and IV Hodgkin Lymphoma
Overview[ - collapse ][ - ]
Purpose | This pilot phase II trial studies how well giving brentuximab vedotin, combination chemotherapy, and radiation therapy works in treating younger patients with stage IIB, IIIB or IV Hodgkin lymphoma. Monoclonal antibodies, such as brentuximab vedotin, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer killing substances to them. Drugs used in chemotherapy, such as etoposide, prednisone, doxorubicin hydrochloride, cyclophosphamide, and dacarbazine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill cancer cells. Giving brentuximab vedotin with combination chemotherapy may kill more cancer cells and reduce the need for radiation therapy. |
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Condition | Stage II Childhood Hodgkin Lymphoma Stage III Childhood Hodgkin Lymphoma Stage IV Childhood Hodgkin Lymphoma |
Intervention | Drug: brentuximab vedotin Drug: etoposide Drug: prednisone Drug: doxorubicin Drug: cyclophosphamide Drug: Dacarbazine(R) Drug: filgrastim Procedure: quality of life assessment Radiation: radiation therapy |
Phase | Phase 2 |
Sponsor | St. Jude Children's Research Hospital |
Responsible Party | St. Jude Children's Research Hospital |
ClinicalTrials.gov Identifier | NCT01920932 |
First Received | August 6, 2013 |
Last Updated | February 6, 2014 |
Last verified | January 2014 |
Tracking Information[ + expand ][ + ]
First Received Date | August 6, 2013 |
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Last Updated Date | February 6, 2014 |
Start Date | August 2013 |
Estimated Primary Completion Date | August 2022 |
Current Primary Outcome Measures | Response rate with PET and CT [Time Frame: after the first 2 cycles of chemotherapy (at approximately 2 months after enrollment)] [Designated as safety issue: No] |
Current Secondary Outcome Measures |
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Descriptive Information[ + expand ][ + ]
Brief Title | Adcetris (Brentuximab Vedotin), Combination Chemotherapy, and Radiation Therapy in Treating Younger Patients With Stage IIB, IIIB and IV Hodgkin Lymphoma |
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Official Title | Adcetris Substituting Vincristine in the OEPA/COPDac Regimen [Treatment Group 3 (TG3) of Euro-Net C1] With Low Dose Tailored-Field Radiation Therapy for Unfavorable Risk Pediatric Hodgkin Lymphoma |
Brief Summary | This pilot phase II trial studies how well giving brentuximab vedotin, combination chemotherapy, and radiation therapy works in treating younger patients with stage IIB, IIIB or IV Hodgkin lymphoma. Monoclonal antibodies, such as brentuximab vedotin, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer killing substances to them. Drugs used in chemotherapy, such as etoposide, prednisone, doxorubicin hydrochloride, cyclophosphamide, and dacarbazine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill cancer cells. Giving brentuximab vedotin with combination chemotherapy may kill more cancer cells and reduce the need for radiation therapy. |
Detailed Description | PRIMARY OBJECTIVES: - To evaluate the safety of brentuximab vedotin, etoposide, prednisone and doxorubicin hydrochloride (AEPA)/cyclophosphamide, brentuximab vedotin, prednisone and dacarbazine (CAPDac), as well as the efficacy (early complete response) after 2 cycles of AEPA chemotherapy in high risk patients with Hodgkin lymphoma (HL). - To compare the event-free survival in high risk HL patients treated with AEPA/CAPDac to the historical control unfavorable risk 2 arm (UR2) of the St. Jude HOD99 study. SECONDARY OBJECTIVES: - To estimate the number of patients with adequate response according to the definitions in the Euro-Net C1 after 2 cycles of AEPA. - To evaluate the safety of Adcetris (brentuximab vedotin) in the AEPA/CAPDac regimen in children with high risk HL. - To describe acute hematologic, neuropathic, and infectious toxicities as they relate to transfusion requirements, growth factor support, episodes of febrile neutropenia and hospitalizations, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. - To study the association between local failure and original lymph node region and volume of radiation (patterns of treatment failure). - To assess patient-reported symptoms and health-related quality of life in children with high risk HL compared to those treated on the unfavorable treatment arm of the St. Jude HOD99 study. OUTLINE: AEPA REGIMEN: Patients receive brentuximab vedotin on days 1, 8, and 15, etoposide on days 1 to 5, prednisone three times daily (TID) on days 1 to 15, and doxorubicin hydrochloride on days 1 and 15. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. CAPDac REGIMEN: Patients receive cyclophosphamide on days 1 and 8, brentuximab vedotin days 1 and 8, prednisone TID on days 1 to 15, and dacarbazine on days 1 to 3. Treatment repeats every 21-28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning 2-3 weeks after CAPDac chemotherapy, patients with lymph nodes that do not go into remission after 2 courses of AEPA chemotherapy undergo radiation therapy daily, 5 days a week for 3-4 weeks. After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 2 years, every 6 months for 2 years, and then annually for 5 years. |
Study Type | Interventional |
Study Phase | Phase 2 |
Study Design | Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment |
Condition |
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Intervention | Drug: brentuximab vedotin Given intravenously (IV). Other Names:
Given IV. Other Names:
Given orally (PO). Other Names: prednisoloneDrug: doxorubicin Given IV. Other Names: Adriamycin(R)Drug: cyclophosphamide Given IV. Other Names: Cytoxan(R)Drug: Dacarbazine(R) Given IV. Other Names: Dimethyl Triazeno Imidazole Carboximide (DTIC)Drug: filgrastim Given subcutaneously (SQ) as clinically indicated. Other Names: Neupogen(R)Procedure: quality of life assessment Quality of life assessment will be done at initial clinical visit, and during chemotherapy, completion of therapy, then at 1 year, 2 years and 5 years. It should take no more than 15-20 minutes to complete. Participation is voluntary by participating institution and by participant. Other Names: Quality of Life AssessmentRadiation: radiation therapy At the end of chemotherapy and recovery of blood counts, radiotherapy will be given to any involved nodes (if any) that are not in complete remission. Other Names:
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Study Arm (s) | Experimental: Treatment Participants receive AEPA regimen (brentuximab vedotin, etoposide, prednisone, doxorubicin), and CAPDac regimen (cyclophosphamide, brentuximab vedotin, prednisone, dacarbazine). Filgrastim may be given as clinically indicated. For those with lymph nodes that do not go into remission after 2 courses of AEPA chemotherapy, radiation therapy will be given. Some participants may volunteer to complete the quality of life assessment. |
Recruitment Information[ + expand ][ + ]
Recruitment Status | Recruiting |
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Estimated Enrollment | 134 |
Estimated Completion Date | August 2022 |
Estimated Primary Completion Date | October 2020 |
Eligibility Criteria | Inclusion Criteria: - Histologically confirmed, previously untreated CD30+ classical Hodgkin Lymphoma (HL). (Participants receiving limited emergent radiation therapy (RT) or steroid therapy - maximum of 7 days - because of cardiopulmonary decompensation or spinal cord compression will be eligible for protocol enrollment). - Age ≤ 18 years at the time of enrollment (i.e., participants are eligible until their 19th birthday). - Ann Arbor stage IIB, IIIB, IVA, or IVB. - Adequate renal function based on GFR ≥ 70 ml/min/1.73m^2 or serum creatinine adjusted for age and gender. - Adequate hepatic function (total bilirubin < 1.5 x ULN for age, and SGOT/SGPT < 2.5 x ULN for age). - Female participant who is post-menarchal must have a negative serum pregnancy test. - Female or male participant of reproductive potential must agree to use an effective contraceptive method throughout duration of study treatment. Exclusion Criteria: - CD30 negative HL. - Has received prior therapy for Hodgkin lymphoma, except as noted above. - Inadequate organ function as described above. - Inability or unwillingness of research participant or legal guardian / representative to give written informed consent. |
Gender | Both |
Ages | N/A |
Accepts Healthy Volunteers | No |
Contacts | Contact: Monika Metzger, MD,MSc 866-278-5833 info@stjude.org |
Location Countries | United States |
Administrative Information[ + expand ][ + ]
NCT Number | NCT01920932 |
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Other Study ID Numbers | HLHR13 |
Has Data Monitoring Committee | Yes |
Information Provided By | St. Jude Children's Research Hospital |
Study Sponsor | St. Jude Children's Research Hospital |
Collaborators | Seattle Genetics, Inc. |
Investigators | Principal Investigator: Monika Metzger, MD,MSc St. Jude Children's Research Hospital |
Verification Date | January 2014 |
Locations[ + expand ][ + ]
St. Jude Children's Research Hospital | Memphis, Tennessee, United States, 38105 Contact: Monika Metzger, MD, MSc | 866-278-5833Principal Investigator: Monika Metzger, MD,MSc Recruiting |
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