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.
ConditionStage II Childhood Hodgkin Lymphoma
Stage III Childhood Hodgkin Lymphoma
Stage IV Childhood Hodgkin Lymphoma
InterventionDrug: brentuximab vedotin
Drug: etoposide
Drug: prednisone
Drug: doxorubicin
Drug: cyclophosphamide
Drug: Dacarbazine(R)
Drug: filgrastim
Procedure: quality of life assessment
Radiation: radiation therapy
PhasePhase 2
SponsorSt. Jude Children's Research Hospital
Responsible PartySt. Jude Children's Research Hospital
ClinicalTrials.gov IdentifierNCT01920932
First ReceivedAugust 6, 2013
Last UpdatedFebruary 6, 2014
Last verifiedJanuary 2014

Tracking Information[ + expand ][ + ]

First Received DateAugust 6, 2013
Last Updated DateFebruary 6, 2014
Start DateAugust 2013
Estimated Primary Completion DateAugust 2022
Current Primary Outcome MeasuresResponse 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
  • Event-free survival [Time Frame: From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment)] [Designated as safety issue: No]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)] [Designated as safety issue: No]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)] [Designated as safety issue: Yes]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)] [Designated as safety issue: No]
  • 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)] [Designated as safety issue: No]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)] [Designated as safety issue: No]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)] [Designated as safety issue: No]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)] [Designated as safety issue: No]Assess and compare the patient reported quality of life and symptom distress to that of patients treated on the HOD 99 unfavorable arm.

Descriptive Information[ + expand ][ + ]

Brief TitleAdcetris (Brentuximab Vedotin), Combination Chemotherapy, and Radiation Therapy in Treating Younger Patients With Stage IIB, IIIB and IV Hodgkin Lymphoma
Official TitleAdcetris 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 TypeInterventional
Study PhasePhase 2
Study DesignEndpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition
  • Stage II Childhood Hodgkin Lymphoma
  • Stage III Childhood Hodgkin Lymphoma
  • Stage IV Childhood Hodgkin Lymphoma
InterventionDrug: brentuximab vedotin
Given intravenously (IV).
Other Names:
  • SGN-35
  • Adcetris(R)
Drug: etoposide
Given IV.
Other Names:
  • VP-16
  • Vepesid(R)
Drug: prednisone
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:
  • irradiation
  • radiotherapy
  • radiation
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 StatusRecruiting
Estimated Enrollment134
Estimated Completion DateAugust 2022
Estimated Primary Completion DateOctober 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.
GenderBoth
AgesN/A
Accepts Healthy VolunteersNo
ContactsContact: Monika Metzger, MD,MSc
866-278-5833
info@stjude.org
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT01920932
Other Study ID NumbersHLHR13
Has Data Monitoring CommitteeYes
Information Provided BySt. Jude Children's Research Hospital
Study SponsorSt. Jude Children's Research Hospital
CollaboratorsSeattle Genetics, Inc.
Investigators Principal Investigator: Monika Metzger, MD,MSc St. Jude Children's Research Hospital
Verification DateJanuary 2014

Locations[ + expand ][ + ]

St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Contact: Monika Metzger, MD, MSc | 866-278-5833
Principal Investigator: Monika Metzger, MD,MSc
Recruiting