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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01026220
First Posted: December 4, 2009
Last Update Posted: May 30, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
December 3, 2009
December 4, 2009
February 8, 2017
May 30, 2017
May 30, 2017
December 2009
March 2012   (Final data collection date for primary outcome measure)
  • Second-event-free Survival [ Time Frame: At 4 years from enrollment ]
    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.
  • 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). ]
    The primary endpoint for safety analysis and monitoring is toxic death, which is death primarily attributable to treatment.
  • Toxic death, defined as death primarily attributable to treatment
  • Early response after 2 courses of ABVE-PC chemotherapy
  • "Second-event"-free survival
Complete list of historical versions of study NCT01026220 on ClinicalTrials.gov Archive Site
  • Event Free Survival [ Time Frame: At 3 years from enrollment ]
    Survival from enrollment to first event: relapse/progression, second malignancy, or death.
  • Second-event-free Survival [ Time Frame: At 4 years from enrollment ]
    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.
  • Event-free Survival for Rapid Early Response (RER) Positron Emission Tomography(PET)-1 Positive, RER PET-1 Negative [ Time Frame: 3 years from enrollment ]
    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.
  • Relapse-free Survival [ Time Frame: 3 years from enrollment ]
    A description, survival to relapse, of patterns of relapse after Doxorubicin, Bleomycin, Vincristine, Etoposide - Prednisone, Cyclophosphamide (ABVE-PC) and risk-adapted radiotherapy.
  • Grade 3 and 4 Non-hematologic Toxicities During Protocol Therapy [ Time Frame: During and after completion of study treatment. ]
    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.
  • Overall Survival [ Time Frame: At 3 years from enrollment ]
    Survival from enrollment to death.
  • Grade 3 and 4 non-hematologic toxicities, specifically GI toxicity and infections
  • Event-free survival
  • Overall Survival
Not Provided
Not Provided
 
Combination Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin Lymphoma
A Non-Randomized Phase III Study of Response Adapted Therapy for the Treatment of Children With Newly Diagnosed High Risk Hodgkin Lymphoma
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.

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.

Interventional
Phase 3
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Childhood Nodular Lymphocyte Predominant Hodgkin Lymphoma
  • Stage III Childhood Hodgkin Lymphoma
  • Stage IV Childhood Hodgkin Lymphoma
  • Biological: bleomycin sulfate
    Given IV or SC
    Other Names:
    • Blenoxane
    • BLEO
    • BLM
  • Drug: doxorubicin hydrochloride
    Given IV
    Other Names:
    • ADM
    • ADR
    • Adria
    • Adriamycin PFS
    • Adriamycin RDF
  • Drug: liposomal vincristine sulfate
    Given IV
    Other Names:
    • liposomal vincristine
    • Marqibo
    • vincristine liposomal
    • vincristine sulfate liposome injection
  • Drug: vinorelbine tartrate
    Given IV
    Other Names:
    • Eunades
    • navelbine ditartrate
    • NVB
    • VNB
  • Drug: cyclophosphamide
    Given IV
    Other Names:
    • CPM
    • CTX
    • Cytoxan
    • Endoxan
    • Endoxana
  • Drug: etoposide phosphate
    Given IV
    Other Names:
    • ETOP
    • Etopophos
  • Drug: prednisone
    Given IV
    Other Names:
    • DeCortin
    • Deltra
  • Biological: filgrastim
    Given IV or SC
    Other Names:
    • G-CSF
    • Neupogen
  • Drug: ifosfamide
    Given IV
    Other Names:
    • Cyfos
    • Holoxan
    • IFF
    • IFX
    • IPP
  • 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.
    Interventions:
    • Biological: bleomycin sulfate
    • Drug: doxorubicin hydrochloride
    • Drug: liposomal vincristine sulfate
    • Drug: cyclophosphamide
    • Drug: etoposide phosphate
    • Drug: prednisone
    • Biological: filgrastim
  • 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.
    Interventions:
    • Biological: bleomycin sulfate
    • Drug: doxorubicin hydrochloride
    • Drug: liposomal vincristine sulfate
    • Drug: vinorelbine tartrate
    • Drug: cyclophosphamide
    • Drug: etoposide phosphate
    • Drug: prednisone
    • Biological: filgrastim
    • Drug: ifosfamide
  • Experimental: Induction: all patient
    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.
    Interventions:
    • Drug: doxorubicin hydrochloride
    • Drug: liposomal vincristine sulfate
    • Drug: cyclophosphamide
    • Drug: etoposide phosphate
    • Drug: prednisone
    • Biological: filgrastim
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
166
September 2015
March 2012   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
up to 21 Years   (Child, Adult)
No
Contact information is only displayed when the study is recruiting subjects
Australia,   Canada,   Israel,   Puerto Rico,   United States
 
 
NCT01026220
AHOD0831
NCI-2011-01994 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000660550
AHOD0831 ( Other Identifier: Children's Oncology Group )
AHOD0831 ( Other Identifier: CTEP )
U10CA098543 ( U.S. NIH Grant/Contract )
Yes
Not Provided
Not Provided
Children's Oncology Group
Children's Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Kara Kelly, MD Children's Oncology Group
Children's Oncology Group
February 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP