Bendamustine Hydrochloride, Rituximab, Etoposide, and Carboplatin in Treating Patients With Relapsed or Refractory Diffuse Large B Cell Lymphoma or Hodgkin Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of Washington
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Washington
ClinicalTrials.gov Identifier:
NCT01165112
First received: June 21, 2010
Last updated: May 6, 2014
Last verified: May 2014
  Purpose

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 relapsed or refractory diffuse large B cell lymphoma or Hodgkin lymphoma. 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, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving bendamustine hydrochloride together with carboplatin, etoposide, and rituximab may kill more cancer cells.


Condition Intervention Phase
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Hodgkin Lymphoma
Drug: bendamustine hydrochloride
Drug: carboplatin
Biological: rituximab
Drug: etoposide
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of Bendamustine/Treanda®, Rituximab, Etoposide, and Carboplatin for Patients With Relapsed or Refractory Lymphoid Malignancies and Select Untreated Lymphomas (TREC)

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Maximally tolerated dose of bendamustine hydrochloride that can be combined with rituximab, carboplatin, and etoposide chemotherapy in patients with relapsed or refractory lymphoid malignancies [ Time Frame: Up to 5 weeks after the last course ] [ Designated as safety issue: Yes ]
    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.

  • Safety and toxicity of this regimen [ Time Frame: Up to 5 weeks after the last course ] [ Designated as safety issue: Yes ]
    The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 will be used to classify and grade toxicities.


Secondary Outcome Measures:
  • Preliminary assessment of the efficacy of this regimen [ Time Frame: Up to 5 weeks after the last course ] [ Designated as safety issue: No ]
    Response will be defined by standard National Cancer Institute (NCI) criteria (Cheson et al) for lymphoid malignancies.

  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 47
Study Start Date: September 2010
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (chemotherapy and monoclonal antibody therapy)
Patients receive bendamustine hydrochloride 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 CD20+ 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.
Drug: bendamustine hydrochloride
Given IV
Other Names:
  • bendamustin hydrochloride
  • bendamustine
  • cytostasan hydrochloride
  • Treanda
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have relapsed or primary refractory lymphomas: diffuse large B cell lymphoma (DLBCL) or Hodgkin's lymphoma (HL); patients with other lymphoid malignancies such as T- cell, or lymphomas that are not curable with anthracycline based therapy (e.g. mantle cell lymphoma [MCL], follicular lymphoma [FL], marginal zone lymphoma [MZL], lymphoplasmacytic lymphoma [LPL]) are eligible with protocol Chair review and approval; note: as of 11/1/12 only patients with typical DLBCL and HL are eligible for enrollment; unusual pathology for DLBCL and HL will require Study Chair approval; the goal is to have 20 patients with DLBCL and 20 patients with HL enrolled
  • World Health Organization (WHO) classification of patient's malignancies must be provided
  • Patients must have measurable disease defined as lesions that can be accurately measured in two dimensions by computed tomography (CT), magnetic resonance imaging (MRI), medical photograph (skin or oral lesion), plain x-ray, or other conventional technique and a greatest transverse diameter of 1 cm or greater; or palpable lesions with both diameters >= 2 cm; Note: CT scans remain the standard for evaluation of nodal disease
  • Patients must have a CT of chest, abdomen, and pelvis within 28 days of enrollment; patients with evidence of lymphadenopathy in the neck must have a CT of neck
  • Patients should not have evidence of active central nervous system lymphoma
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Absolute neutrophil count (ANC) >= 1,500/mm^3 (without transfusion or growth factor support); exception: patients with cytopenias due to disease, that do not meet these criteria, will be considered eligible with review and approval by the principal investigator (PI) or Co-PI prior to study entry
  • Platelets >= 100,000/mm^3 (without transfusion or growth factor support); exception: patients with cytopenias due to disease, that do not meet these criteria, will be considered eligible with review and approval by the PI or Co-PI prior to study entry
  • Serum creatinine < 1.5 mg/dl or creatinine clearance greater than 50/ ml per minute
  • Total bilirubin < 1.5 times upper limit of normal
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 times upper limit of normal
  • Patients must have a serum lactate dehydrogenase (LDH) performed within 14 days prior to registration
  • All patients must be informed of the investigational nature of this study and have given written consent in accordance with institutional and federal guidelines
  • Patients must be anticipated to complete at least 2 cycles of chemotherapy

Exclusion Criteria:

  • Patients known positive for human immunodeficiency virus (HIV), or infectious hepatitis type B or C
  • Pregnant or nursing women; men or women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
  • Patients with other prior malignancies except for adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, breast or cervical cancer in situ, or other cancer from which the patient has been disease-free for 5 years or greater, unless approved by the protocol Chair
  • Patients who are refractory (i.e. not responded or progressed within 6 months) to a carboplatin, cisplatin, bendamustine, or etoposide-based regimen
  • Patients who have other medical conditions that would contraindicate treatment with aggressive chemotherapy (including active infection, uncontrolled hypertension, congestive heart failure, unstable angina pectoris, or myocardial infarction within the past 6 months, uncontrolled arrhythmia); if the patient's cardiac history is questionable, a measurement of left ventricular ejection fraction should be obtained within 42 days prior to registration; patients with left ventricular ejection fraction < 50% are not eligible
  • Autologous or allogeneic transplantation within 12 months or radioimmunotherapy within 6 months of registration; prior failed (< 5x10^6 CD34/kg) peripheral blood stem cell (PBSC) collection
  • Patients who had pelvic radiation within 12 months or received more than 2 prior therapies with myelotoxic regimens; single agent monoclonal antibody treatment is not considered as one therapy; radiation treatment following chemotherapy is not considered as one separated therapy; consolidative therapy will be considered one regimen e.g. salvage therapy followed by conditioning regimen and transplant
  • Previous chemotherapy/immunotherapy within 3 weeks before study entry
  • Concurrent use of other anti-cancer agents or experimental treatments
  • Known hypersensitivity to bendamustine, mannitol, etoposide, carboplatin, or rituximab
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01165112

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Ajay K. Gopal    206-288-2037      
Principal Investigator: Ajay K. Gopal         
Sponsors and Collaborators
University of Washington
Investigators
Principal Investigator: Ajay Gopal Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT01165112     History of Changes
Other Study ID Numbers: PSOC 2502, NCI-2010-00907, PSOC 2502, P30CA015704
Study First Received: June 21, 2010
Last Updated: May 6, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Antibodies
Antibodies, Monoclonal
Rituximab
Etoposide
Etoposide phosphate
Bendamustine
Nitrogen Mustard Compounds
Carboplatin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents

ClinicalTrials.gov processed this record on July 26, 2014