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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by St. Jude Children's Research Hospital
Sponsor:
Collaborator:
Seattle Genetics, Inc.
Information provided by (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
  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.


Condition Intervention Phase
Stage II Childhood Hodgkin Lymphoma
Stage III Childhood Hodgkin Lymphoma
Stage IV Childhood Hodgkin Lymphoma
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 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

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 ]

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.


Estimated Enrollment: 134
Study Start Date: August 2013
Estimated Study Completion Date: August 2022
Estimated Primary Completion Date: October 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: 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 Name: prednisolone
Drug: doxorubicin
Given IV.
Other Name: Adriamycin(R)
Drug: cyclophosphamide
Given IV.
Other Name: Cytoxan(R)
Drug: Dacarbazine(R)
Given IV.
Other Name: Dimethyl Triazeno Imidazole Carboximide (DTIC)
Drug: filgrastim
Given subcutaneously (SQ) as clinically indicated.
Other Name: 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 Name: Quality of Life Assessment
Radiation: 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

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

Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01920932

Contacts
Contact: Monika Metzger, MD,MSc 866-278-5833 info@stjude.org

Locations
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Monika Metzger, MD, MSc    866-278-5833      
Principal Investigator: Monika Metzger, MD,MSc         
Sponsors and Collaborators
St. Jude Children's Research Hospital
Seattle Genetics, Inc.
Investigators
Principal Investigator: Monika Metzger, MD,MSc St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT01920932     History of Changes
Other Study ID Numbers: HLHR13
Study First Received: August 6, 2013
Last Updated: February 6, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by St. Jude Children's Research Hospital:
Pediatric cancer
Hodgkin lymphoma
Targeted therapy
Frontline therapy
Brentuximab vedotin
Quality of Life
OEPA/COPDac

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Dacarbazine
Liposomal doxorubicin
Etoposide phosphate
Doxorubicin
Etoposide
Prednisolone
Prednisone
Lenograstim
Antibodies, Monoclonal
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on July 31, 2014