Clinical trial NCT01920932: Adcetris (Brentuximab Vedotin), Combination Chemotherapy, and Radiation Therapy in Treating Younger Patients With Stage IIB, IIIB and IV Hodgkin Lymphoma
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Stage II Childhood Hodgkin Lymphoma
Stage III Childhood Hodgkin Lymphoma
Stage IV Childhood Hodgkin Lymphoma
Keywords: Pediatric cancer
Hodgkin lymphoma
Targeted therapy
Frontline therapy
Brentuximab vedotin
Quality of Life
OEPA/COPDac
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
Collaborators: name: Seagen Inc.
First posted: 2013-08-12
Enrollment: 77
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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.

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.

Primary outcomes:
measure: Percentage of Initially Enrolled Patients That Have a Complete Response at Early Response Assessment Compared to Historical Control
timeFrame: After the first 2 cycles of chemotherapy (at approximately 2 months after enrollment)
measure: Percentage of Initially Enrolled Patients That Have a Complete Response at Early Response Assessment Compared to Historical Control
timeFrame: After the first 2 cycles of chemotherapy (at approximately 2 months after enrollment)
measure: Complete Response Rate Estimate for All Evaluable Participants
timeFrame: After the first 2 cycles of chemotherapy (at 2 months from enrollment for each participant)
measure: 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).
timeFrame: From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment)
Secondary outcomes:
measure: Local Failure Rate in High Risk HL Patients Treated With AEPA/CAPDac.
timeFrame: From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment)
measure: Descriptive of Hematological Adverse Events
timeFrame: From enrollment to end of therapy (approximately 8 months)
measure: Descriptive of Infectious Adverse Events
timeFrame: From enrollment to end of therapy (approximately 8 months)
measure: Descriptive of Neuropathic Adverse Events
timeFrame: From enrollment to end of therapy (approximately 8 months)
measure: 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)
timeFrame: 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)
measure: 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)
timeFrame: 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)
measure: Response Rate
timeFrame: after the first 2 cycles of chemotherapy (at approximately 2 months after enrollment)
measure: Patient Quality of Life (QoL)
timeFrame: At various time points from diagnosis through 5 years off therapy. (up to approximately 6 years from enrollment).
measure: Parent Proxy Quality of Life (QoL)
timeFrame: At various time points from diagnosis through 5 years off therapy. (up to approximately 6 years from enrollment)
measure: Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points
timeFrame: At various time points from diagnosis through 5 years off therapy. (up to approximately 6 years from enrollment)
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital Stanford University
state: California
city: Peoria
country: United States
facility: St. Jude Midwest Affiliate
state: Illinois
city: Scarborough
country: United States
facility: Maine Children's Cancer Program (MCCP)
state: Maine
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Harvard Cancer Center
state: Massachusetts
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Matt Ehrhardt, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Metzger ML, Link MP, Billett AL, Flerlage J, Lucas JT Jr, Mandrell BN, Ehrhardt MJ, Bhakta N, Yock TI, Friedmann AM, de Alarcon P, Luna-Fineman S, Larsen E, Kaste SC, Shulkin B, Lu Z, Li C, Hiniker SM, Donaldson SS, Hudson MM, Krasin MJ. Excellent Outcome for Pediatric Patients With High-Risk Hodgkin Lymphoma Treated With Brentuximab Vedotin and Risk-Adapted Residual Node Radiation. J Clin Oncol. 2021 Jul 10;39(20):2276-2283. doi: 10.1200/JCO.20.03286. Epub 2021 Apr 7.