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

NCT01920932 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 2 other identifiers: HLHR13NCI-2013-01123
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 6

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.

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

Outcome Measures

Primary Outcomes (4)

• Percentage of Initially Enrolled Patients That Have a Complete Response at Early Response Assessment Compared to Historical Control

  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.

  After the first 2 cycles of chemotherapy (at approximately 2 months after enrollment)

• Percentage of Initially Enrolled Patients That Have a Complete Response at Early Response Assessment Compared to Historical Control

  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 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.

  After the first 2 cycles of chemotherapy (at approximately 2 months after enrollment)

• Complete Response Rate Estimate for All Evaluable Participants

  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).

  After the first 2 cycles of chemotherapy (at 2 months from enrollment for each participant)

• 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).

  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).

  From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment)

Secondary Outcomes (10)

• 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)

Study Arms (1)

Treatment

EXPERIMENTAL

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.

Drug: brentuximab vedotin; Drug: etoposide; Drug: prednisone; Drug: doxorubicin; Drug: cyclophosphamide; Drug: Dacarbazine(R); Drug: filgrastim; Other: quality of life assessment; Radiation: radiation therapy

Interventions

brentuximab vedotin DRUG

Given intravenously (IV).

Also known as: SGN-35, Adcetris(R)

Treatment

etoposide DRUG

Given IV.

Also known as: VP-16, Vepesid(R)

Treatment

prednisone DRUG

Given orally (PO).

Also known as: prednisolone

Treatment

doxorubicin DRUG

Given IV.

Also known as: Adriamycin(R)

Treatment

cyclophosphamide DRUG

Given IV.

Also known as: Cytoxan(R)

Treatment

Dacarbazine(R) DRUG

Given IV.

Also known as: Dimethyl Triazeno Imidazole Carboximide (DTIC)

Treatment

filgrastim DRUG

Given subcutaneously (SQ) as clinically indicated.

Also known as: Neupogen(R)

Treatment

quality of life assessment OTHER

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.

Treatment

radiation therapy RADIATION

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.

Also known as: irradiation, radiotherapy, radiation

Treatment

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• Seagen Inc.: collaborator

Study Sites (6)

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, 94304, United States

Location

St. Jude Midwest Affiliate

Peoria, Illinois, 61637, United States

Location

Maine Children's Cancer Program (MCCP)

Scarborough, Maine, 04704, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Harvard Cancer Center

Boston, Massachusetts, 02115, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Publications (2)

• Castellino SM, Giulino-Roth L, Harker-Murray P, Kahn JM, Forlenza C, Cho S, Hoppe B, Parsons SK, Kelly KM; COG Hodgkin Lymphoma Committee. Children's Oncology Group's 2023 blueprint for research: Hodgkin lymphoma. Pediatr Blood Cancer. 2023 Sep;70 Suppl 6(Suppl 6):e30580. doi: 10.1002/pbc.30580. Epub 2023 Jul 28.

  PMID: 37505794 DERIVED

• 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.

  PMID: 33826362 DERIVED

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Neoplasms; Hodgkin Disease

Interventions

Brentuximab Vedotin; Etoposide; Prednisone; Prednisolone; Doxorubicin; Cyclophosphamide; Dacarbazine; Filgrastim; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienetriols; Daunorubicin; Anthracyclines; Naphthacenes; Aminoglycosides; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Biological Factors; Therapeutics; Physical Phenomena

Results Point of Contact

• Title: Matt Ehrhardt, MD
• Organization: St. Jude Children's Research Hospital

matt.ehrhardt@stjude.org

(901) 595-5913

Study Officials

• Matt Ehrhardt, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2013
• First Posted: August 12, 2013
• Study Start: August 12, 2013
• Primary Completion: November 16, 2020
• Study Completion (Estimated): May 1, 2028
• Last Updated: May 6, 2026
• Results First Posted: February 8, 2022

Record last verified: 2026-04

Locations

US (6)