Clinical Trial: Adcetris (Brentuximab Vedotin), Combination Chemotherapy, and Radiation Therapy in Treating Younger Patients With Stage IIB, IIIB and IV Hodgkin Lymphoma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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 Pediatri

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 Summary:

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 bren
Sponsor: St. Jude Children's Research Hospital

Current Primary Outcome:

• Response rate with PET and CT [ Time Frame: after the first 2 cycles of chemotherapy (at approximately 2 months after enrollment) ]
  The first 32 evaluable participants enrolled will be evaluated for this objective.
• Event-free survival [ Time Frame: From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment) ]
  Time to event defined as relapse, progression or death.
• Response rate with PET and CT [ Time Frame: after the first 2 cycles of chemotherapy (approximately 2 months after last participant is enrolled) ]
  All participants enrolled will be evaluated for this objective following completion of the first 2 cycles of chemotherapy.

Original Primary Outcome: Response rate with PET and CT [ Time Frame: after the first 2 cycles of chemotherapy (at approximately 2 months after enrollment) ]

Current Secondary Outcome:

• Response rate [ Time Frame: after the first 2 cycles of chemotherapy (at approximately 2 months after enrollment) ]
  Response compared to the Euro-Net C1 after 2 cycles of AEPA.
• Number of adverse events [ Time Frame: From enrollment to end of therapy (approximately 8 months) ]
  According to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.
• Local failure rate [ Time Frame: From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment) ]
• Patient quality of life (QoL) [ Time Frame: At various time points from diagnosis through 5 years off therapy. (up to approximately 6 years from enrollment) ]

  Patient QOL will be measured at multiple time points to assess the patient's physical emotional, social, and school functioning. Time references below are to the approximate time of measurement after start of therapy (baseline). Each course is approximately 1 month:

  At Diagnosis (baseline) (T1), Course 1 Day 8 (T2), Course 1 Day 15 (T3), Course 2 Day 1 (T4), Course 2 Day 15 (T5), Course 3 Day 1 (T6) Course 3 Day 8 (T7), Course 6 Day 1 (T8) and Course 6 Day 8 (T9), 4-6 weeks after chemotherapy (approximately 7-8 months) for those without radiation (T10), 4-6 weeks after radiation (approximately 9-10 months) (T11), 1 year off therapy (approximately 1 year and 8 months (T12), 2 years off therapy (approximately 2 years and 8 months) (T13), and 5 years off therapy (approximately 5 years and 8 months) (T14).

• Parent proxy quality of life (QoL) [ Time Frame: At various time points from diagnosis through 5 years off therapy. (up to approximately 6 years from enrollment) ]

  Parent's assessment of child's physical, emotional, social and school functioning over multiple time points. Time references below are to the approximate time of measurement after start of therapy (baseline). Each course is approximately 1 month:

  At Diagnosis (baseline) (T1), Course 1 Day 8 (T2), Course 1 Day 15 (T3), Course 2 Day 1 (T4), Course 2 Day 15 (T5), Course 3 Day 1 (T6) Course 3 Day 8 (T7), Course 6 Day 1 (T8) and Course 6 Day 8 (T9), 4-6 weeks after chemotherapy (approximately 7-8 months) for those without radiation (T10), 4-6 weeks after radiation (approximately 9-10 months) (T11), 1 year off therapy (approximately 1 year and 8 months (T12), 2 years off therapy (approximately 2 years and 8 months) (T13), and 5 years off therapy (approximately 5 years and 8 months) (T14).

• Correlation of agreement between patient QoL and parent proxy QoL at multiple time points [ Time Frame: At various time points from diagnosis through 5 years off therapy. (up to approximately 6 years from enrollment) ]

  Assess and compare the patient reported and parent proxy quality of life across multiple time points. Time references below are to the approximate time of measurement after start of therapy (baseline). Each course is approximately 1 month:

  At Diagnosis (baseline) (T1), Course 1 Day 8 (T2), Course 1 Day 15 (T3), Course 2 Day 1 (T4), Course 2 Day 15 (T5), Course 3 Day 1 (T6) Course 3 Day 8 (T7), Course 6 Day 1 (T8) and Course 6 Day 8 (T9), 4-6 weeks after chemotherapy (approximately 7-8 months) for those without radiation (T10), 4-6 weeks after radiation (approximately 9-10 months) (T11), 1 year off therapy (approximately 1 year and 8 months (T12), 2 years off therapy (approximately 2 years and 8 months) (T13), and 5 years off therapy (approximately 5 years and 8 months) (T14).

• Correlation of agreement between patient QoL and symptom distress to patients treated on HOD 99 unfavorable at multiple time points [ Time Frame: At Diagnosis (baseline) (T1), completion of 2 cycles of chemotherapy (approximately 2 months) (T2), completion of 4 cycles of chemotherapy (approximately 4 months) (T3), completion of radiation (approximately 8 months) (T4) ]
  Assess and compare the patient reported quality of life and symptom distress to that of patients treated on the HOD 99 unfavorable arm.

Original Secondary Outcome:

• Event-free survival [ Time Frame: From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment) ]
  Time to event defined as relapse, progression or death.
• Response rate [ Time Frame: after the first 2 cycles of chemotherapy (at approximately 2 months after enrollment) ]
  Response compared to the Euro-Net C1 after 2 cycles of AEPA.
• Number of adverse events [ Time Frame: From enrollment to end of therapy (approximately 8 months) ]
  According to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.
• Local failure rate [ Time Frame: From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment) ]
• Patient quality of life (QoL) [ Time Frame: At various time points from diagnosis through 5 years off therapy. (up to approximately 6 years from enrollment) ]

  Patient QOL will be measured at multiple time points to assess the patient's physical emotional, social, and school functioning. Time references below are to the approximate time of measurement after start of therapy (baseline). Each course is approximately 1 month:

  At Diagnosis (baseline) (T1), Course 1 Day 8 (T2), Course 1 Day 15 (T3), Course 2 Day 1 (T4), Course 2 Day 15 (T5), Course 3 Day 1 (T6) Course 3 Day 8 (T7), Course 6 Day 1 (T8) and Course 6 Day 8 (T9), 4-6 weeks after chemotherapy (approximately 7-8 months) for those without radiation (T10), 4-6 weeks after radiation (approximately 9-10 months) (T11), 1 year off therapy (approximately 1 year and 8 months (T12), 2 years off therapy (approximately 2 years and 8 months) (T13), and 5 years off therapy (approximately 5 years and 8 months) (T14).

• Parent proxy quality of life (QoL) [ Time Frame: At various time points from diagnosis through 5 years off therapy. (up to approximately 6 years from enrollment) ]

  Parent's assessment of child's physical, emotional, social and school functioning over multiple time points. Time references below are to the approximate time of measurement after start of therapy (baseline). Each course is approximately 1 month:

  At Diagnosis (baseline) (T1), Course 1 Day 8 (T2), Course 1 Day 15 (T3), Course 2 Day 1 (T4), Course 2 Day 15 (T5), Course 3 Day 1 (T6) Course 3 Day 8 (T7), Course 6 Day 1 (T8) and Course 6 Day 8 (T9), 4-6 weeks after chemotherapy (approximately 7-8 months) for those without radiation (T10), 4-6 weeks after radiation (approximately 9-10 months) (T11), 1 year off therapy (approximately 1 year and 8 months (T12), 2 years off therapy (approximately 2 years and 8 months) (T13), and 5 years off therapy (approximately 5 years and 8 months) (T14).

• Correlation of agreement between patient QoL and parent proxy QoL at multiple time points [ Time Frame: At various time points from diagnosis through 5 years off therapy. (up to approximately 6 years from enrollment) ]

  Assess and compare the patient reported and parent proxy quality of life across multiple time points. Time references below are to the approximate time of measurement after start of therapy (baseline). Each course is approximately 1 month:

  At Diagnosis (baseline) (T1), Course 1 Day 8 (T2), Course 1 Day 15 (T3), Course 2 Day 1 (T4), Course 2 Day 15 (T5), Course 3 Day 1 (T6) Course 3 Day 8 (T7), Course 6 Day 1 (T8) and Course 6 Day 8 (T9), 4-6 weeks after chemotherapy (approximately 7-8 months) for those without radiation (T10), 4-6 weeks after radiation (approximately 9-10 months) (T11), 1 year off therapy (approximately 1 year and 8 months (T12), 2 years off therapy (approximately 2 years and 8 months) (T13), and 5 years off therapy (approximately 5 years and 8 months) (T14).

• Correlation of agreement between patient QoL and symptom distress to patients treated on HOD 99 unfavorable at multiple time points [ Time Frame: At Diagnosis (baseline) (T1), completion of 2 cycles of chemotherapy (approximately 2 months) (T2), completion of chemotherapy (approximately 6 months) (T3), completion of radiation (approximately 8 months) (T4) ]
  Assess and compare the patient reported quality of life and symptom distress to that of patients treated on the HOD 99 unfavorable arm.

Information By: St. Jude Children's Research Hospital

Dates:
Date Received: August 6, 2013
Date Started: August 12, 2013
Date Completion: April 30, 2025
Last Updated: April 10, 2017
Last Verified: September 2016