NCT01026220 · CITED IN SOURCE DOCUMENTS

Combination Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin Lymphoma

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2022-04-28

This phase III trial is studying how well giving combination chemotherapy together with radiation therapy works in treating young patients with newly diagnosed Hodgkin 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 combination chemotherapy together with radiation therapy may kill more cancer cells.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Second-event-free Survival

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outcome · POSTED

Safety Analysis and Monitoring of Toxic Death

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outcome · POSTED

Event Free Survival

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outcome · POSTED

Second-event-free Survival

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outcome · POSTED

Event-free Survival for Rapid Early Response (RER) Positron Emission Tomography(PET)-1 Positive, RER PET-1 Negative

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outcome · POSTED

Relapse-free Survival

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outcome · POSTED

Event Free Survival

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outcome · POSTED

Grade 3 and 4 Non-hematologic Toxicities During Protocol Therapy

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outcome · POSTED

Overall Survival

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Pathologically confirmed newly diagnosed Hodgkin lymphoma (HL) meeting one of the following criteria: * Classical disease * Nodular lymphocyte-predominant disease * Stage III or IV disease with B symptoms, as defined by ≥ 1 of the following: * Unexplained weight loss \> 10% within the past 6 months * Unexplained recurrent fever \> 38°C within the past month * Recurrent drenching night sweats within the past month * Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR maximum serum creatinine based on age/gender as follows: * 0.4 mg/dL (1 to 5 months) * 0.5 mg/dL (6 to 11 months) * 0.6 mg/dL (12 to 23 months) * 0.8 mg/dL (2 to 5 years) * 1 mg/dL (6 to 9 years) * 1.2 mg/dL (10 to 12 years) * 1.5 mg/dL (males) or 1.4 mg/dL (females) (13 to 15 years) * 1.7 mg/dL (males) or 1.4 mg/dL (females) (≥ 16 years) * Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age * AST or ALT \< 2.5 times ULN for age * Shortening fraction ≥ 27% by ECHO OR ejection fraction ≥ 50% by MUGA (unless due to large mediastinal mass from HL) * FEV\_1/FVC \> 60% by pulmonary function tests (PFT) (unless due to large mediastinal mass fromHL) * For children who are unable to cooperate for PFTs, the criteria are: * No evidence of dyspnea at rest * No exercise intolerance * Pulse oximetry \> 92% on room air * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No pathologic prolongation of QTc interval (\> 450 milliseconds) on 12-lead ECG * No prior chemotherapy, biological response modifiers (e.g., monoclonal antibody therapy), or radiotherapy * At least 28 days since prior corticosteroids except for emergent treatment for respiratory distress or spinal cord compression, or for treatment of allergy to contrast agent required for CT scan * No other concurrent cancer chemotherapy or immunomodulating agents (including steroids) * Concurrent corticosteroid therapy as treatment or prophylaxis for anaphylactic reactions allowed * No concurrent pegfilgrastim
healthy Volunteers: false
maximum Age: 21 Years
sex: ALL
std Ages: CHILD
ADULT

Treatment arms and interventions

arm Groups

description
Patients receive 2 more courses of ABVE-PC comprising doxorubicin hydrochloride IV over 1-120 minutes and cyclophosphamide IV over 30-60 minutes on days 1 and 2; bleomycin sulfate IV over at least 10 minutes or subcutaneously (SC) and vincristine sulfate IV on days 1 and 8; etoposide IV over 1-2 hours on days 1-3; oral prednisone twice daily on days 1-7; and filgrastim SC or IV daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression.
intervention Names
Biological: bleomycin sulfate
Drug: doxorubicin hydrochloride
Drug: liposomal vincristine sulfate
Drug: cyclophosphamide
Drug: etoposide phosphate
Drug: prednisone
Biological: filgrastim
label
Regimen I (consolidation therapy)
type
EXPERIMENTAL
description
Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, and filgrastim SC or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.
intervention Names
Biological: bleomycin sulfate
Drug: doxorubicin hydrochloride
Drug: liposomal vincristine sulfate
Drug: vinorelbine tartrate
Drug: cyclophosphamide
Drug: etoposide phosphate
Drug: prednisone
Biological: filgrastim
Drug: ifosfamide
label
Regimen II (consolidation therapy)
type
EXPERIMENTAL
description
All patients receive ABVE-PC induction therapy then they are assigned to Group 2 (RER), Group 3 (SER) or taken off study if they develop progressive disease.
intervention Names
Drug: doxorubicin hydrochloride
Drug: liposomal vincristine sulfate
Drug: cyclophosphamide
Drug: etoposide phosphate
Drug: prednisone
Biological: filgrastim
label
Induction: all patient
type
EXPERIMENTAL

interventions

arm Group Labels
Regimen I (consolidation therapy)
Regimen II (consolidation therapy)
description
Given IV or SC
name
bleomycin sulfate
other Names
Blenoxane
BLEO
BLM
type
BIOLOGICAL
arm Group Labels
Induction: all patient
Regimen I (consolidation therapy)
Regimen II (consolidation therapy)
description
Given IV
name
doxorubicin hydrochloride
other Names
ADM
ADR
Adria
Adriamycin PFS
Adriamycin RDF
type
DRUG
arm Group Labels
Induction: all patient
Regimen I (consolidation therapy)
Regimen II (consolidation therapy)
description
Given IV
name
liposomal vincristine sulfate
other Names
liposomal vincristine
Marqibo
vincristine liposomal
vincristine sulfate liposome injection
type
DRUG
arm Group Labels
Regimen II (consolidation therapy)
description
Given IV
name
vinorelbine tartrate
other Names
Eunades
navelbine ditartrate
NVB
VNB
type
DRUG
arm Group Labels
Induction: all patient
Regimen I (consolidation therapy)
Regimen II (consolidation therapy)
description
Given IV
name
cyclophosphamide
other Names
CPM
CTX
Cytoxan
Endoxan
Endoxana
type
DRUG
arm Group Labels
Induction: all patient
Regimen I (consolidation therapy)
Regimen II (consolidation therapy)
description
Given IV
name
etoposide phosphate
other Names
ETOP
Etopophos
type
DRUG
arm Group Labels
Induction: all patient
Regimen I (consolidation therapy)
Regimen II (consolidation therapy)
description
Given IV
name
prednisone
other Names
DeCortin
Deltra
type
DRUG
arm Group Labels
Induction: all patient
Regimen I (consolidation therapy)
Regimen II (consolidation therapy)
description
Given IV or SC
name
filgrastim
other Names
G-CSF
Neupogen
type
BIOLOGICAL
arm Group Labels
Regimen II (consolidation therapy)
description
Given IV
name
ifosfamide
other Names
Cyfos
Holoxan
IFF
IFX
IPP
type
DRUG

Study design

allocation

NON_RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 166
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Second event here is defined as any relapse/progression of Hodgkin Lymphoma (HL) or a previously reported second malignant neoplasm (SMN), a new SMN, or death after a first event which can be relapse/progression of HL, SMN, biopsy-proven HL following completion of Consolidation for Slow Early Response (SER) patient, positive bilateral bone marrow biopsy following completion of Consolidation for Stage IV patient, or death. If death occurs as the 1st event, it also counts as the 2nd event.
measure
Second-event-free Survival
time Frame
At 4 years from enrollment
description
The primary endpoint for safety analysis and monitoring is toxic death, which is death primarily attributable to treatment.
measure
Safety Analysis and Monitoring of Toxic Death
time Frame
Within 30 days of protocol treatment at median follow-up of 48 months (range: 1 to 70 months).

secondary Outcomes

description
Survival from enrollment to first event: relapse/progression, second malignancy, or death.
measure
Event Free Survival
time Frame
At 3 years from enrollment
description
Second event here is defined as any relapse/progression of Hodgkin Lymphoma (HL) or a previously reported second malignant neoplasm (SMN), a new SMN, or death after a first event which can be relapse/progression of HL, SMN, biopsy-proven HL following completion of Consolidation for Slow Early Response (SER) patient, positive bilateral bone marrow biopsy following completion of Consolidation for Stage IV patient, or death. If death occurs as the 1st event, it also counts as the 2nd event.
measure
Second-event-free Survival
time Frame
At 4 years from enrollment
description
To investigate whether very early response assessment measured by Fluorodeoxyglucose-PET after 1 cycle of chemotherapy identifies a subject cohort that can be studied in future trials and that is distinguishable from currently defined RER after 2 cycles.
measure
Event-free Survival for Rapid Early Response (RER) Positron Emission Tomography(PET)-1 Positive, RER PET-1 Negative
time Frame
3 years from enrollment
description
A description, survival to relapse, of patterns of relapse after Doxorubicin, Bleomycin, Vincristine, Etoposide - Prednisone, Cyclophosphamide (ABVE-PC) and risk-adapted radiotherapy.
measure
Relapse-free Survival
time Frame
3 years from enrollment
description
The number of patients that experience Common Terminology Criteria (CTC) Version 4 grade 3 or higher non-hematologic toxicity at any time during protocol therapy.
measure
Grade 3 and 4 Non-hematologic Toxicities During Protocol Therapy
time Frame
During and after completion of study treatment.
description
Survival from enrollment to death.
measure
Overall Survival
time Frame
At 3 years from enrollment

Full study description

brief Summary: This phase III trial is studying how well giving combination chemotherapy together with radiation therapy works in treating young patients with newly diagnosed Hodgkin 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 combination chemotherapy together with radiation therapy may kill more cancer cells.
detailed Description: PRIMARY OBJECTIVES: I. To maintain the overall survival (as defined by 4-year "second-event" free survival) for subjects with high risk Hodgkin lymphoma at or above 95%. SECONDARY OBJECTIVES: I. To maintain 3-year event-free survival for subjects with high risk Hodgkin lymphoma at or above 93%. II. To maintain comparable overall survival (as defined by 4-year "second-event" free survival) between subjects with high risk Hodgkin lymphoma who have a rapid or slow response to the initial 2 cycles of ABVE-PC\* by intensifying therapy through the addition of 2 cycles of ifosfamide/vinorelbine in those with a slow early response. III. To investigate whether very early response assessment measured by FDG-PET after 1 cycle of chemotherapy identifies a subject cohort that can be studied in future trials and that is distinguishable from currently defined RER after 2 cycles. IV. To describe the patterns of relapse after ABVE-PC\* and risk-adapted radiotherapy. OUTLINE: This is a multicenter study. INDUCTION THERAPY (ABVE-PC): Patients receive doxorubicin hydrochloride IV over 1-120 minutes and cyclophosphamide IV over 30-60 minutes on days 1 and 2, bleomycin sulfate IV over at least 10 minutes or subcutaneously (SC) and vincristine sulfate IV on days 1 and 8, etoposide phosphate IV over 1-2 hours on days 1-3, oral prednisone twice daily on days 1-7, and filgrastim\* SC or IV daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. NOTE: \*Patients do not receive filgrastim on day 8. Patients undergo clinical restaging and response assessment after 2 courses of induction therapy. Patients with rapid early response (RER) or slow early response (SER) proceed to consolidation therapy. Patients with progressive disease go off study. CONSOLIDATION THERAPY: Patients are assigned to 1 of 2 consolidation therapy regimens based on response to induction therapy. Patients who develop progressive disease after induction are taken off protocol therapy. REGIMEN I (RER): Patients receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression. REGIMEN II (SER): Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-30 minutes on days 1 and 5, and filgrastim SC or IV daily beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression. Patients with a continued response after completion of consolidation therapy proceed to risk-adapted radiotherapy. RISK-ADAPTED RADIOTHERAPY: Beginning at 3 weeks after completion of consolidation chemotherapy, patients undergo radiotherapy once daily, 5 days a week, for 3 weeks (14 fractions) in the absence of unacceptable toxicity or disease progression. Patients classified as RER receive radiation therapy only to sites of bulky disease. Patients classified as SER receive radiation therapy to sites of bulky disease and areas that remain FDG-PET avid after induction therapy. After completion of study therapy, patients are followed up periodically for 10 years.

Source references

references

citation
Tie X, Shin M, Lee C, Perlman SB, Huemann Z, Weisman AJ, Castellino SM, Kelly KM, McCarten KM, Alazraki AL, Hu J, Cho SY, Bradshaw TJ. Automatic Quantification of Serial PET/CT Images for Pediatric Hodgkin Lymphoma Using a Longitudinally Aware Segmentation Network. Radiol Artif Intell. 2025 May;7(3):e240229. doi: 10.1148/ryai.240229.
pmid
39969278
type
DERIVED
citation
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
type
DERIVED