Adcetris (Brentuximab Vedotin), Substituting Vincristine in the OEPA/COPDac Regimen [Treatment Group 3 (TG3) of Euro-Net C1] With Involved Node Radiation Therapy for High Risk Pediatric Hodgkin Lymphoma (HL)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 77
- 试验地点
- 12
- 主要终点
- Complete Response Rate Estimate for All Evaluable Participants
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 diagnosis (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 urine or serum pregnancy test.
- •Female or male participant of reproductive potential must agree to use an effective contraceptive method throughout duration of study treatment.
排除标准
- •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.
研究组 & 干预措施
Treatment
Participants receive AEPA regimen (brentuximab vedotin, etoposide, prednisone, doxorubicin), and CAPDac regimen (cyclophosphamide, brentuximab vedotin, prednisone, dacarbazine(R)). 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.
干预措施: radiation therapy (Radiation)
Treatment
Participants receive AEPA regimen (brentuximab vedotin, etoposide, prednisone, doxorubicin), and CAPDac regimen (cyclophosphamide, brentuximab vedotin, prednisone, dacarbazine(R)). 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.
干预措施: Dacarbazine(R) (Drug)
Treatment
Participants receive AEPA regimen (brentuximab vedotin, etoposide, prednisone, doxorubicin), and CAPDac regimen (cyclophosphamide, brentuximab vedotin, prednisone, dacarbazine(R)). 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.
干预措施: quality of life assessment (Other)
Treatment
Participants receive AEPA regimen (brentuximab vedotin, etoposide, prednisone, doxorubicin), and CAPDac regimen (cyclophosphamide, brentuximab vedotin, prednisone, dacarbazine(R)). 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.
干预措施: brentuximab vedotin (Drug)
Treatment
Participants receive AEPA regimen (brentuximab vedotin, etoposide, prednisone, doxorubicin), and CAPDac regimen (cyclophosphamide, brentuximab vedotin, prednisone, dacarbazine(R)). 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.
干预措施: etoposide (Drug)
Treatment
Participants receive AEPA regimen (brentuximab vedotin, etoposide, prednisone, doxorubicin), and CAPDac regimen (cyclophosphamide, brentuximab vedotin, prednisone, dacarbazine(R)). 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.
干预措施: doxorubicin (Drug)
Treatment
Participants receive AEPA regimen (brentuximab vedotin, etoposide, prednisone, doxorubicin), and CAPDac regimen (cyclophosphamide, brentuximab vedotin, prednisone, dacarbazine(R)). 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.
干预措施: prednisone (Drug)
Treatment
Participants receive AEPA regimen (brentuximab vedotin, etoposide, prednisone, doxorubicin), and CAPDac regimen (cyclophosphamide, brentuximab vedotin, prednisone, dacarbazine(R)). 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.
干预措施: cyclophosphamide (Drug)
Treatment
Participants receive AEPA regimen (brentuximab vedotin, etoposide, prednisone, doxorubicin), and CAPDac regimen (cyclophosphamide, brentuximab vedotin, prednisone, dacarbazine(R)). 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.
干预措施: filgrastim (Drug)
结局指标
主要结局
Complete Response Rate Estimate for All Evaluable Participants
时间窗: After the first 2 cycles of chemotherapy (at 2 months from enrollment for each participant)
To evaluate the safety of AEPA/CAPDac, as well as the efficacy (early complete response) after 2 cycles of AEPA chemotherapy in high-risk patients with Hodgkin Lymphoma (HL).
Comparison of the Event-free (EFS) Survival in High Risk HL Patients Treated With AEPA/CAPDac to the Historical Control HOD99 Unfavorable Risk 2 Arm (UR2).
时间窗: From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment)
Event-free survival (EFS) is defined as the probability of survival between the date of study enrollment to the date of first event (relapsed or progressive disease, second malignancy, or death from any cause) or to last follow-up for patients without events. Under the proportional hazard model assumption, the two-sample log-rank test used to compare the EFS between HLHR13 and historical control of HOD99 unfavorable risk 2 arm (UR2).
Percentage of Initially Enrolled Patients That Have a Complete Response at Early Response Assessment Compared to Historical Control
时间窗: After the first 2 cycles of chemotherapy (at approximately 2 months after enrollment)
To determine the efficacy of 2 cycles of AEPA chemotherapy, the response rate for the first 32 evaluable participants enrolled was evaluated. If it shown efficacy (detect 20% increase complete rate with 80% power and 5% type I error compared with the proportion of historical control of HOD99 (NCT00145600) unfavorable risk patients had complete rate at week 8 of 17% (24/141), the response results will be reported in a national/international meeting and the study will continue to enroll for a total of 77 patients.
次要结局
- Local Failure Rate in High Risk HL Patients Treated With AEPA/CAPDac.(From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment))
- Descriptive of Hematological Adverse Events(From enrollment to end of therapy (approximately 8 months))
- Descriptive of Infectious Adverse Events(From enrollment to end of therapy (approximately 8 months))
- Descriptive of Neuropathic Adverse Events(From enrollment to end of therapy (approximately 8 months))
- To Assess the Patient Reported Symptoms and Health-related Quality of Life in Children With High Risk HL Compared to Those Treated on the Unfavorable HOD99 Treatment Arm (UR2) at Multiple Time Points. (PedsQL v.3.0)(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))
- To Assess the Patient Reported Symptoms and Health-related Quality of Life in Children With High Risk HL Compared to Those Treated on the Unfavorable HOD99 Treatment Arm (UR2) at Multiple Time Points. (PedsQL v.4.0)(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))
- Response Rate(after the first 2 cycles of chemotherapy (at approximately 2 months after enrollment))
- Patient Quality of Life (QoL)(At various time points from diagnosis through 5 years off therapy. (up to approximately 6 years from enrollment).)
- Parent Proxy Quality of Life (QoL)(At various time points from diagnosis through 5 years off therapy. (up to approximately 6 years from enrollment))
- Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points(At various time points from diagnosis through 5 years off therapy. (up to approximately 6 years from enrollment))