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A Phase II Study of Bortezomib (Velcade, PS-341, IND #58443) in Combination With Ifosfamide/Vinorelbine in Pediatric Patients and Young Adults With Refractory/Recurrent Hodgkin Disease

Phase 2
29 Years
Not Enrolling
Adult Lymphocyte Depletion Hodgkin Lymphoma, Adult Lymphocyte Predominant Hodgkin Lymphoma, Adult Mixed Cellularity Hodgkin Lymphoma, Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma, Adult Nodular Sclerosis Hodgkin Lymphoma, Childhood Lymphocyte Depletion Hodgkin Lymphoma, Childhood Lymphocyte Predominant Hodgkin Lymphoma, Childhood Mixed Cellularity Hodgkin Lymphoma, Childhood Nodular Lymphocyte Predominant Hodgkin Lymphoma, Childhood Nodular Sclerosis Hodgkin Lymphoma, Recurrent Adult Hodgkin Lymphoma, Recurrent/Refractory Childhood Hodgkin Lymphoma, Stage I Adult Hodgkin Lymphoma, Stage I Childhood Hodgkin Lymphoma, Stage II Adult Hodgkin Lymphoma, Stage II Childhood Hodgkin Lymphoma, Stage III Adult Hodgkin Lymphoma, Stage III Childhood Hodgkin Lymphoma, Stage IV Adult Hodgkin Lymphoma, Stage IV Childhood Hodgkin Lymphoma

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Trial Information

A Phase II Study of Bortezomib (Velcade, PS-341, IND #58443) in Combination With Ifosfamide/Vinorelbine in Pediatric Patients and Young Adults With Refractory/Recurrent Hodgkin Disease


I. Determine the efficacy and safety of bortezomib (as a chemosensitizing agent) in
pediatric patients and young adults with primary refractory Hodgkin's lymphoma (HL) or HL in
first relapse.

II. Determine response rate in patients treated with bortezomib, ifosfamide, and vinorelbine
ditartrate (vinorelbine tartrate) (IVB) and compare it to the historical response rate in
patients treated with ifosfamide and vinorelbine ditartrate alone.


I. Determine the overall response rate (complete and partial response) and induction success
rate after 2 or 4 courses of therapy and the reinduction rate (complete response) after 4
courses of therapy.

II. Determine the proportion of patients able to mobilize sufficient hematopoietic stem
cells (CD34+) after 2 courses of IVB.

OUTLINE: This is a multicenter, open-label, pilot study.

Patients receive ifosfamide intravenously (IV) continuously over days 1-4, vinorelbine
tartrate IV over 6-10 minutes on days 1 and 5, bortezomib IV on days 1, 4, and 8, and
filgrastim (G-CSF) IV or subcutaneously beginning on day 6 and continuing until blood counts
recover or peripheral blood stem cells (PBSC) are harvested. Treatment repeats every 21 days
for up to 2 or 4 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo autologous PBSC harvesting according to institutional guidelines after the
second course of therapy.

After completion of study treatment, patients are followed every 6 months for 2 years and
then annually thereafter.

Inclusion Criteria:

- Histologically confirmed Hodgkin's lymphoma at time of relapse or disease
progression, meeting all of the following criteria:

- Stage I-IV disease

- No morphologically unclassifiable disease

- Meets 1 of the following criteria:

- Mixed cellularity

- Lymphocytic depletion (LD)

- LD, diffuse fibrosis

- LD, reticular

- Lymphocyte predominance (LP)

- LP, diffuse

- LP, nodular

- Nodular sclerosis (NS)

- NS, cellular phase

- NS, lymphocytic predominance

- NS, mixed cellularity

- NS, LD

- Not otherwise specified

- Primary refractory disease OR disease in first relapse, except for the following:

- Patients achieving a complete response after treatment on protocol COG-AHOD0431
who experience a biopsy-proven recurrence after doxorubicin hydrochloride,
vincristine, prednisone, and cyclophosphamide without involved-field

- Patients on the observation-only arm of protocol COG-AHOD0431

- Any measurable, focal mass lesion of a visceral organ (e.g., liver, spleen, or

- Patients with metastatic disease to bone marrow and granulocytopenia, anemia, and/or
thrombocytopenia are allowed provided both of the following criteria are met:

- Platelet count ≥ 20,000/mm³ (platelet transfusion allowed)

- Hemoglobin ≥ 8 g/dL (packed red blood cell transfusion allowed)

- Karnofsky performance status (PS) 60-100% (for patients > 16 years of age) OR Lanksy
PS 60-100% (for patients =< 16 years of age)

- Life expectancy >= 2 months

- Absolute neutrophil count >= 1,000/mm^3

- Platelet count >= 75,000/mm^3 (transfusion independent) (for patients with no bone
marrow involvement)

- Creatinine =< 1.5 times upper limit of normal (ULN)

- Creatinine clearance or radioisotope glomerular filtration rate >= 70 mL/min/1.73 m^2

- AST and ALT =< 2.5 times ULN

- Bilirubin =< 1.5 times ULN

- Shortening fraction >= 27% by echocardiogram OR LVEF >= 50% by gated radionuclide

- Patients with a seizure disorder are eligible if on a nonenzyme-inducing
anticonvulsant and seizures are well controlled

- No CNS toxicity > grade 2

- No serious intercurrent illnesses

- No known hypersensitivity to E. coli-derived proteins, filgrastim (G-CSF), or any
component of the study drugs

- No peripheral neuropathy > grade 1

- No known hypersensitivity to bortezomib, boron, or mannitol

- No other concurrent chemotherapy or immunomodulating agents (including steroids)

- Concurrent corticosteroids allowed for treatment or prophylaxis of anaphylactic

- No dexamethasone or aprepitant as an antiemetic

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Recovered from prior therapy

- No prior bortezomib or other proteasome inhibitors

- At least 3 weeks since prior chemotherapy (4 weeks for nitrosoureas)

- More than 14 days since prior investigational drugs

- No concurrent enzyme inducing anticonvulsants that alter p450 metabolism, including
phenytoin, carbamazepine, phenobarbital, or other anticonvulsants

- Benzodiazepine or gabapentin allowed

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Comparison of complete response between IVB and historical controls of IV after 2 courses

Outcome Description:

Compared using a two sample test for proportions. 95% confidence interval will be calculated.

Outcome Time Frame:

At 42 days

Safety Issue:


Principal Investigator

Terzah Horton

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

January 2007

Completion Date:

Related Keywords:

  • Adult Lymphocyte Depletion Hodgkin Lymphoma
  • Adult Lymphocyte Predominant Hodgkin Lymphoma
  • Adult Mixed Cellularity Hodgkin Lymphoma
  • Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma
  • Adult Nodular Sclerosis Hodgkin Lymphoma
  • Childhood Lymphocyte Depletion Hodgkin Lymphoma
  • Childhood Lymphocyte Predominant Hodgkin Lymphoma
  • Childhood Mixed Cellularity Hodgkin Lymphoma
  • Childhood Nodular Lymphocyte Predominant Hodgkin Lymphoma
  • Childhood Nodular Sclerosis Hodgkin Lymphoma
  • Recurrent Adult Hodgkin Lymphoma
  • Recurrent/Refractory Childhood Hodgkin Lymphoma
  • Stage I Adult Hodgkin Lymphoma
  • Stage I Childhood Hodgkin Lymphoma
  • Stage II Adult Hodgkin Lymphoma
  • Stage II Childhood Hodgkin Lymphoma
  • Stage III Adult Hodgkin Lymphoma
  • Stage III Childhood Hodgkin Lymphoma
  • Stage IV Adult Hodgkin Lymphoma
  • Stage IV Childhood Hodgkin Lymphoma
  • Hodgkin Disease
  • Lymphoma
  • Sclerosis



Children's Oncology Group Arcadia, California  91006-3776