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A Non-Randomized Phase III Study of Response Adapted Therapy for the Treatment of Children With Newly Diagnosed High Risk Hodgkin Lymphoma

Phase 3
21 Years
Open (Enrolling)
Childhood Nodular Lymphocyte Predominant Hodgkin Lymphoma, Stage III Childhood Hodgkin Lymphoma, Stage IV Childhood Hodgkin Lymphoma

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Trial Information

A Non-Randomized Phase III Study of Response Adapted Therapy for the Treatment of Children With Newly Diagnosed High Risk Hodgkin Lymphoma


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%.


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.

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

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.

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 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

- 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

- Concurrent corticosteroid therapy as treatment or prophylaxis for anaphylactic
reactions allowed

- No concurrent pegfilgrastim

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Second-event-free survival at or above 95%

Outcome Time Frame:

4 years

Safety Issue:


Principal Investigator

Kara Kelly

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

December 2009

Completion Date:

Related Keywords:

  • Childhood Nodular Lymphocyte Predominant Hodgkin Lymphoma
  • Stage III Childhood Hodgkin Lymphoma
  • Stage IV Childhood Hodgkin Lymphoma
  • Hodgkin Disease
  • Lymphoma



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