This phase I/II trial is studying the side effects and best dose of bendamustine hydrochloride when given together with carboplatin, etoposide, and rituximab in treating patients with diffuse large B cell lymphoma or Hodgkin lymphoma that has come back after a period of improvement or has not responded to previous treatment. Drugs used in chemotherapy, such as bendamustine hydrochloride, etoposide, and carboplatin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, may block cancer growth by targeting certain cells. Giving bendamustine hydrochloride together with carboplatin, etoposide, and rituximab may kill more cancer cells.
PRIMARY OBJECTIVES: I. To estimate the maximally tolerated dose of bendamustine (bendamustine hydrochloride) that can be combined with rituximab, carboplatin, and etoposide chemotherapy in patients with relapsed or refractory lymphoid malignancies. II. To determine the safety and toxicity of the above regimen. SECONDARY OBJECTIVES: I. To gain a preliminary assessment of the efficacy of the above regimen. II. To determine the ability to proceed to peripheral blood stem cell collection following the above regimen (the impact of above regimen on stem cell reserve). III. To investigate whether findings from laboratory, radiographic or pathologic studies have any prognostic impact on the response to treatment. OUTLINE: This is a phase I, dose-escalation study of bendamustine hydrochloride followed by a phase II study. Patients receive bendamustine hydrochloride intravenously (IV) over 30-60 minutes on days 1 and 2, etoposide IV over 60 minutes on days 1-3, and carboplatin IV over 60 minutes on day 1. Patients with cluster of differentiation (CD)20+ T-cell lymphoma disease also receive rituximab IV on day 2 or 3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 4 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
48
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States
Maximally Tolerated Dose of Bendamustine Hydrochloride That Can be Combined With Rituximab, Carboplatin, and Etoposide Chemotherapy in Patients With Relapsed or Refractory Lymphoid Malignancies
Defined as dose at which approximately =\< 25% of patients experience a DLT. Following completed observation of final patient, two-parameter logistic model fit to data, generating dose-response curve based on observed toxicity rate at dose levels visited. Based on this fitted model, MTD is estimated to be dose that is associated with toxicity rate of 25%. If estimate of slope parameter for fitted curve is not positive and finite, geometric mean of dose level used for last cohort and dose level that would have been assigned to next cohort is taken as MTD.
Time frame: Up to 5 weeks after the last course
Safety and Toxicity of This Regimen
Count of participants experiencing a dose limiting toxicity. The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0 will be used to classify and grade toxicities.
Time frame: Up to 5 weeks after the last course
Preliminary Assessment of the Efficacy of This Regimen
Response will be defined by standard NCI criteria (Cheson et al) for lymphoid malignancies.
Time frame: Up to 5 weeks after the last course
Ability to Proceed to Peripheral Blood Stem Cell (PBSC) Collection Following Treatment (Impact of This Regimen on Stem Cell Reserve)
Time frame: Up to 5 weeks after the last course
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