Combination Chemotherapy Followed by Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin's Lymphoma

NCT00302003 | Completed Phase 3 Results DMC

• 5 other identifiers: AHOD0431NCI-2009-00377CDR0000459962U10CA098543COG-AHOD0431
• Study Type: interventional
• Target: 287
• Locations: 1 country
• Sites: 1

Brief Summary

This phase III trial is studying how well combination chemotherapy works when given before radiation therapy and/or additional chemotherapy in treating young patients with newly diagnosed Hodgkin's lymphoma. Drugs used in chemotherapy 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 more than one drug (combination chemotherapy) and giving them together with radiation therapy may kill more cancer cells.

Conditions

Childhood Favorable Prognosis Hodgkin Lymphoma; Childhood Lymphocyte Depletion Hodgkin Lymphoma; Childhood Mixed Cellularity Hodgkin Lymphoma; Childhood Nodular Sclerosis Hodgkin Lymphoma; Stage I Childhood Hodgkin Lymphoma; Stage II Childhood Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (3)

• Event Free Survival Without Receiving Radiation Therapy (EFSnoRT).

  Survival is defined as the minimum time from study entry to requirement for additional chemotherapy and IFRT for retrieval, occurrence of a second malignant neoplasm, or death from any cause. Patients without report of such events where censored at last contact. Patients who achieve less than CR after 3 cycles of AV-PC will require IFRT and hence will satisfy this definition at the time of response evaluation. Patients who achieve a CR but who relapse will receive addition chemotherapy and IFRT or intense retrieval and hence will satisfy this definition at the time of the first relapse of Hodgkin disease. This endpoint will be used to compute event free survival without receiving radiation therapy (EFSnoRT).

  At 60 months

• Intensive Therapy Free Survival (ITFS).

  Survival is defined as the minimum time from study entry to a relapse of higher risk at any time, any relapse following treatment with protocol mandated IFRT, death from any cause, or the occurrence of a second malignant neoplasm. This will be used to compute intensive therapy free survival (ITFS). Patients without report of such events where censored at last contact. This differs from traditional EFS in that relapse after AVPC\* x3 therapy alone that does not place the patient in a higher risk category is not considered a treatment failure. In this definition, higher-risk relapse refers to relapse involving sites and extent of disease that place the patient in the current COG definition of intermediate or high-risk disease. If a patient with CR who experiences a LR relapse is not retreated with protocol-mandated chemotherapy and IFRT, subsequent disease relapses will nevertheless be counted in the analysis of the treatment strategy.

  At 60 months

• Event Free Survival (EFS)

  Survival is defined as the minimum time from study entry to a relapse of any kind, death from any cause, or occurrence of a second malignant neoplasm. Patients without report of such events where censored at last contact. This will be used to compute event free survival (EFS).

  At 60 months

Secondary Outcomes (1)

• Overall Survival

  At 60 months

Study Arms (1)

Doxorubicin, Vincristine, Cyclophosphamide and Filgrastim

EXPERIMENTAL

Treatment consists of 3 cycles of Doxorubicin hydrochloride IV (25 mg/m2) days 1 \& 2, Vincristine sulfate IV (1.4 mg/m2 \[max 2.8 mg\]) Days 1 \& 8, Prednisone orally (40 mg/m2) Days 1-7, Cyclophosphamide IV (600 mg/m2) Days 1 \& 2, Filgrastim by mouth or IV (5 micrograms/kg/dose) 24 hours after Cyclophosphamide complete. See detailed description for remainder of therapy.

Radiation: radiation therapy; Drug: doxorubicin hydrochloride; Drug: vincristine sulfate; Drug: prednisone; Drug: cyclophosphamide; Drug: ifosfamide; Drug: vinorelbine tartrate; Drug: dexamethasone; Drug: etoposide phosphate; Drug: cisplatin; Drug: cytarabine; Biological: filgrastim

Interventions

radiation therapy RADIATION

Undergo radiation therapy

Also known as: irradiation, radiotherapy, therapy, radiation

Doxorubicin, Vincristine, Cyclophosphamide and Filgrastim

doxorubicin hydrochloride DRUG

Given IV

Also known as: ADM, ADR, Adria, Adriamycin PFS, Adriamycin RDF

Doxorubicin, Vincristine, Cyclophosphamide and Filgrastim

vincristine sulfate DRUG

Given IV

Also known as: leurocristine sulfate, VCR, Vincasar PFS

Doxorubicin, Vincristine, Cyclophosphamide and Filgrastim

prednisone DRUG

Given orally

Also known as: DeCortin, Deltra

Doxorubicin, Vincristine, Cyclophosphamide and Filgrastim

cyclophosphamide DRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana

Doxorubicin, Vincristine, Cyclophosphamide and Filgrastim

ifosfamide DRUG

Given IV

Also known as: Cyfos, Holoxan, IFF, IFX, IPP

Doxorubicin, Vincristine, Cyclophosphamide and Filgrastim

vinorelbine tartrate DRUG

Given IV

Also known as: Eunades, navelbine ditartrate, NVB, VNB

Doxorubicin, Vincristine, Cyclophosphamide and Filgrastim

dexamethasone DRUG

Given IV

Also known as: Aeroseb-Dex, Decaderm, Decadron, DM, DXM

Doxorubicin, Vincristine, Cyclophosphamide and Filgrastim

etoposide phosphate DRUG

Given IV

Also known as: ETOP, Etopophos

Doxorubicin, Vincristine, Cyclophosphamide and Filgrastim

cisplatin DRUG

Given IV

Also known as: CACP, CDDP, CPDD, DDP

Doxorubicin, Vincristine, Cyclophosphamide and Filgrastim

cytarabine DRUG

Given IV

Also known as: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside

Doxorubicin, Vincristine, Cyclophosphamide and Filgrastim

filgrastim BIOLOGICAL

Given IV or subcutaneously

Also known as: G-CSF, Neupogen

Doxorubicin, Vincristine, Cyclophosphamide and Filgrastim

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Histologically confirmed Hodgkin's lymphoma meeting the following criteria:
• Newly diagnosed disease
• Stage IA OR stage IIA without bulky disease
• No lymphocyte-predominant histology
• Staging on this study will be determined by the clinical stage; surgical staging is strongly discouraged, except for the rare situation of equivocal imaging studies below the diaphragm
• Patients may not have received any previous chemotherapy or radiation therapy; patients may not have received systemic corticosteroids within 30 days of enrollment on this protocol; steroids used for treatment of contrast agent allergy required for computed tomography (CT) scans are acceptable
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^3
• Total bilirubin =\< 1.5 x normal
• Alanine (ALT) =\< 2.5 x normal
• Shortening fraction \>= 27% by echocardiogram OR ejection fraction \>= 50% by multi-gated acquisition (MUGA)
• No pathologic prolongation of QTc interval on 12-lead electrocardiography (ECG)
• Female patients of childbearing potential must have a negative pregnancy test
• Lactating females must agree that they will not breastfeed a child while on this study
• Fertile patients must use effective contraception
• Males and females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method

Sponsors & Collaborators

• Children's Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Children's Oncology Group

Arcadia, California, 91006-3776, 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

• Parekh A, Keller FG, McCarten KM, Kessel S, Cho S, Pei Q, Wu Y, Castellino SM, Constine LS, Schwartz CL, Hodgson D, Kelly KM, Hoppe BS. Targeted radiotherapy for early-stage, low-risk pediatric Hodgkin lymphoma slow early responders: a COG AHOD0431 analysis. Blood. 2022 Sep 8;140(10):1086-1093. doi: 10.1182/blood.2022016098.

  PMID: 35763667 DERIVED

Related Links

• Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive

MeSH Terms

Conditions

Hodgkin Disease

Interventions

Radiotherapy; Radiation; Doxorubicin; Vincristine; Prednisone; Cyclophosphamide; Ifosfamide; indolepropanol phosphate; Vinorelbine; Dexamethasone; Calcium Dobesilate; etoposide phosphate; Cisplatin; Cytarabine; Filgrastim; Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Pregnadienetriols; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Results Reporting Coordinator
• Organization: Children's Oncology Group

resultsreportingcoordinator@childrensoncologygroup.org

626-447-0064

Study Officials

• Frank Keller, MD

  Children's Oncology Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2006
• First Posted: March 13, 2006
• Study Start: February 1, 2006
• Primary Completion: March 1, 2012
• Study Completion: June 30, 2019
• Last Updated: March 30, 2021
• Results First Posted: February 9, 2017

Record last verified: 2016-08

Locations

US (1)