Combination Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin Lymphoma - Full Text View

Purpose

RATIONALE: 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.

PURPOSE: 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.

Condition	Intervention	Phase
Lymphoma	Biological: bleomycin sulfate Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: etoposide Drug: ifosfamide Drug: prednisone Drug: vincristine sulfate Drug: vinorelbine tartrate	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Masking: Open Label Primary Purpose: Treatment
Official Title:	A Non-Randomized Phase III Study of Response Adapted Therapy for the Treatment of Children With Newly Diagnosed High Risk Hodgkin Lymphoma

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Toxic death, defined as death primarily attributable to treatment [ Designated as safety issue: Yes ]
Early response after 2 courses of ABVE-PC chemotherapy [ Designated as safety issue: No ]
"Second-event"-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Grade 3 and 4 non-hematologic toxicities, specifically gastrointestinal toxicity and infections [ Designated as safety issue: Yes ]
Event-free survival [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]

Estimated Enrollment:	165
Study Start Date:	December 2009
Estimated Primary Completion Date:	September 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Regimen I (consolidation therapy) 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.	Biological: bleomycin sulfate Given IV Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: etoposide Given IV Drug: prednisone Given orally Drug: vincristine sulfate Given IV
Experimental: Regimen II (consolidation therapy) 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.	Biological: bleomycin sulfate Given IV Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: etoposide Given IV Drug: ifosfamide Given IV Drug: prednisone Given orally Drug: vincristine sulfate Given IV Drug: vinorelbine tartrate Given IV

Arms

Assigned Interventions

Experimental: Regimen I (consolidation therapy)

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.

Biological: bleomycin sulfate

Given IV

Drug: cyclophosphamide

Given IV

Drug: doxorubicin hydrochloride

Given IV

Drug: etoposide

Given IV

Drug: prednisone

Given orally

Drug: vincristine sulfate

Given IV

Experimental: Regimen II (consolidation therapy)

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.

Biological: bleomycin sulfate

Given IV

Drug: cyclophosphamide

Given IV

Drug: doxorubicin hydrochloride

Given IV

Drug: etoposide

Given IV

Drug: ifosfamide

Given IV

Drug: prednisone

Given orally

Drug: vincristine sulfate

Given IV

Drug: vinorelbine tartrate

Given IV

Detailed Description:

OBJECTIVES:

Primary

To maintain the overall survival (as defined by 4-year "second-event"-free survival) at or above 95% for pediatric patients with high-risk Hodgkin lymphoma (HL).

Secondary

To maintain 3-year event-free survival at or above 93% for patients with high-risk HL.
To maintain comparable overall survival (as defined by 4-year "second-event"-free survival) between patients with high-risk HL who have a rapid or slow response to the initial 2 courses of ABVE-PC chemotherapy by intensifying therapy through the addition of 2 courses of ifosfamide/vinorelbine in those with a slow early response.
To investigate whether very early response assessment measured by FDG-PET scan after 1 course of ABVE-PC chemotherapy identifies a patient cohort that can be studied in future trials and that is distinguishable from currently defined rapid early response after 2 courses.
To describe the patterns of relapse after ABVE-PC chemotherapy 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.
- 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.

After completion of study therapy, patients are followed up periodically for 10 years.

Eligibility

Ages Eligible for Study:	up to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

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 from HL)
- 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

PRIOR CONCURRENT THERAPY:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01026220

Show 168 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Kara Kelly, MD

Herbert Irving Comprehensive Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Gregory H. Reaman, Children's Oncology Group - Group Chair Office
ClinicalTrials.gov Identifier:	NCT01026220 History of Changes
Other Study ID Numbers:	CDR0000660550, COG-AHOD0831
Study First Received:	December 3, 2009
Last Updated:	August 3, 2012
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

childhood nodular lymphocyte predominant Hodgkin lymphoma
stage III childhood Hodgkin lymphoma
stage IV childhood Hodgkin lymphoma

Additional relevant MeSH terms:

Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bleomycin
Doxorubicin
Etoposide phosphate
Isophosphamide mustard
Vinorelbine
Cyclophosphamide
Etoposide

Ifosfamide
Prednisone
Vincristine
Vinblastine
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 23, 2013