Gemcitabine and Bendamustine in Patients With Relapsed or Refractory Hodgkin's Lymphoma

PRIMARY OBJECTIVES:

I. To evaluate the toxicity and determine the maximum tolerated dose (MTD) of combined
bendamustine (bendamustine hydrochloride) and gemcitabine (gemcitabine hydrochloride) in
patients with relapsed or refractory Hodgkin's lymphoma.

II. To determine the overall response rate of bendamustine and gemcitabine in patients with
relapsed and refractory Hodgkin's lymphoma.

SECONDARY OBJECTIVES:

I. To determine whether therapy with bendamustine in the setting of relapsed or refractory
Hodgkin's lymphoma will impact future stem cell collection.

OUTLINE: This is a phase I, dose-escalation study of bendamustine hydrochloride followed by a
phase II study.

Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on day 1 and
bendamustine hydrochloride IV over 30 minutes on days 1 and 2. Treatment repeats every 21-28
days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3-6 months for 2 years,
then every 6 months for up to 3 years.

Inclusion Criteria:

- Histologically documented Classical Hodgkin's lymphoma that is recurrent or refractory
after standard chemotherapy; core biopsies are acceptable if they contain adequate
tissue for primary diagnosis and immunophenotyping; bone marrow biopsies as the sole
means of diagnosis are not acceptable

- Patients with Hodgkin's lymphoma may have one of the following World Health
Organization subtypes:

- Nodular sclerosis Hodgkin's lymphoma

- Lymphocyte-rich Hodgkin's lymphoma

- Mixed cellularity Hodgkin's lymphoma

- Lymphocyte depletion Hodgkin's lymphoma

- Nodular lymphocyte predominant Hodgkin's lymphoma

- Patients must have relapsed or progressed after at least one prior therapy

- Patients with relapsed or refractory disease following stem cell transplantation are
permitted

- No prior treatment with bendamustine; prior therapy with gemcitabine is permitted

- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

- Measurable disease must be present either on physical examination or imaging studies;
non-measurable disease alone is not acceptable

- Measurable disease: lesions that can be accurately measured in at least two dimensions
as >= 1.0 x 1.0 cm by computerized tomography (CT), PET/CT (positron emission
tomography/CT), or magnetic resonance imaging (MRI)

- Non-measurable disease: all other lesions, including small lesions (less than 1.0 x
1.0 cm) and truly non-measurable lesions; lesions that are considered non-measurable
include the following:

- Bone lesions (lesions if present should be noted)

- Ascites

- Pleural/pericardial effusion

- Lymphangitis cutis/pulmonis

- Bone marrow (involvement by Hodgkin's lymphoma should be noted)

- Non-pregnant and non-nursing; due to the teratogenic potential of these agents,
pregnant or nursing patients may not be enrolled; women and men of reproductive
potential should agree to use an effective means of birth control

- Patients with human immunodeficiency virus (HIV) infection are eligible; patients with
HIV infection must meet the following: No evidence of co-infection with hepatitis B or
C; cluster of differentiation (CD)4+ count >= 400/mm; no evidence of resistant strains
of HIV; on anti-HIV therapy with an HIV viral load < 50 copies HIV ribonucleic acid
(RNA)/mL; no history of acquired immune deficiency syndrome (AIDS) defining conditions

- Granulocytes >= 1000/μl

- Platelet count >= 75,000/μl

- Creatinine =< 20 mg/dL

- Bilirubin =< 2.0 mg/dL

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.0 x upper
limits of normal