Bendamustine Hydrochloride, Rituximab, Etoposide, and Carboplatin in Treating Patients With Relapsed or Refractory Lymphoid Malignancies and Select Untreated Lymphomas
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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 lymphoid malignancies and select untreated lymphomas. 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 |
|---|---|---|
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Adult Grade III Lymphomatoid Granulomatosis Adult Nasal Type Extranodal NK/T-cell Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Chronic Lymphocytic Leukemia Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma Contiguous Stage II Adult Lymphoblastic Lymphoma Contiguous Stage II Grade 1 Follicular Lymphoma Contiguous Stage II Grade 2 Follicular Lymphoma Contiguous Stage II Grade 3 Follicular Lymphoma Contiguous Stage II Mantle Cell Lymphoma Contiguous Stage II Marginal Zone Lymphoma Contiguous Stage II Small Lymphocytic Lymphoma Cutaneous B-cell Non-Hodgkin Lymphoma Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Intraocular Lymphoma Nodal Marginal Zone B-cell Lymphoma Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma Noncontiguous Stage II Adult Lymphoblastic Lymphoma Noncontiguous Stage II Grade 1 Follicular Lymphoma Noncontiguous Stage II Grade 2 Follicular Lymphoma Noncontiguous Stage II Grade 3 Follicular Lymphoma Noncontiguous Stage II Mantle Cell Lymphoma Noncontiguous Stage II Marginal Zone Lymphoma Noncontiguous Stage II Small Lymphocytic Lymphoma Recurrent Adult Burkitt Lymphoma Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Adult Diffuse Mixed Cell Lymphoma Recurrent Adult Diffuse Small Cleaved Cell Lymphoma Recurrent Adult Grade III Lymphomatoid Granulomatosis Recurrent Adult Hodgkin Lymphoma Recurrent Adult Immunoblastic Large Cell Lymphoma Recurrent Adult Lymphoblastic Lymphoma Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Mycosis Fungoides/Sezary Syndrome Recurrent Small Lymphocytic Lymphoma Small Intestine Lymphoma Splenic Marginal Zone Lymphoma Stage I Adult Burkitt Lymphoma Stage I Adult Diffuse Mixed Cell Lymphoma Stage I Adult Diffuse Small Cleaved Cell Lymphoma Stage I Adult Immunoblastic Large Cell Lymphoma Stage I Adult Lymphoblastic Lymphoma Stage I Cutaneous T-cell Non-Hodgkin Lymphoma Stage I Grade 1 Follicular Lymphoma Stage I Grade 2 Follicular Lymphoma Stage I Grade 3 Follicular Lymphoma Stage I Mantle Cell Lymphoma Stage I Marginal Zone Lymphoma Stage I Mycosis Fungoides/Sezary Syndrome Stage I Small Lymphocytic Lymphoma Stage II Adult Burkitt Lymphoma Stage II Cutaneous T-cell Non-Hodgkin Lymphoma Stage II Grade 1 Follicular Lymphoma Stage II Grade 2 Follicular Lymphoma Stage II Grade 3 Follicular Lymphoma Stage II Mycosis Fungoides/Sezary Syndrome Stage III Adult Burkitt Lymphoma Stage III Adult Diffuse Mixed Cell Lymphoma Stage III Adult Diffuse Small Cleaved Cell Lymphoma Stage III Adult Immunoblastic Large Cell Lymphoma Stage III Adult Lymphoblastic Lymphoma Stage III Cutaneous T-cell Non-Hodgkin Lymphoma Stage III Grade 1 Follicular Lymphoma Stage III Grade 2 Follicular Lymphoma Stage III Grade 3 Follicular Lymphoma Stage III Mantle Cell Lymphoma Stage III Marginal Zone Lymphoma Stage III Mycosis Fungoides/Sezary Syndrome Stage III Small Lymphocytic Lymphoma Stage IV Adult Burkitt Lymphoma Stage IV Adult Diffuse Mixed Cell Lymphoma Stage IV Adult Diffuse Small Cleaved Cell Lymphoma Stage IV Adult Immunoblastic Large Cell Lymphoma Stage IV Adult Lymphoblastic Lymphoma Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma Stage IV Grade 1 Follicular Lymphoma Stage IV Grade 2 Follicular Lymphoma Stage IV Grade 3 Follicular Lymphoma Stage IV Mantle Cell Lymphoma Stage IV Marginal Zone Lymphoma Stage IV Mycosis Fungoides/Sezary Syndrome Stage IV Small Lymphocytic Lymphoma Waldenström Macroglobulinemia |
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) |
- 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 3-5 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 3-5 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.
- Preliminary assessment of the efficacy of this regimen [ Time Frame: Up to 3-5 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: After completion of study treatment ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 47 |
| Study Start Date: | September 2010 |
| Estimated Primary Completion Date: | September 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
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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.
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Drug: bendamustine hydrochloride
Given IV
Other Names:
Drug: carboplatin
Given IV
Other Names:
Biological: rituximab
Given IV
Other Names:
Drug: etoposide
Given IV
Other Names:
Other: laboratory biomarker analysis
Correlative studies
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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 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.
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 |
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: the goal is to have a minimum of 20 patients with DLBCL and 20 patients with HL
- 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 or Co-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| 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 | |
| Principal Investigator: | Ajay Gopal | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium |
More Information
No publications provided
| ClinicalTrials.gov Identifier: | NCT01165112 History of Changes |
| Other Study ID Numbers: | PSOC 2502, NCI-2010-00907 |
| Study First Received: | June 21, 2010 |
| Last Updated: | March 13, 2013 |
| Health Authority: | United States: Institutional Review Board |
Additional relevant MeSH terms:
|
Burkitt Lymphoma Hodgkin Disease Immunoblastic Lymphadenopathy Leukemia Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Lymphoma Lymphoma, Follicular Lymphoma, Non-Hodgkin Lymphomatoid Granulomatosis Waldenstrom Macroglobulinemia Mycoses Mycosis Fungoides Sezary Syndrome Lymphoma, B-Cell |
Lymphoma, Large B-Cell, Diffuse Lymphoma, Large-Cell, Immunoblastic Precursor Cell Lymphoblastic Leukemia-Lymphoma Lymphoma, T-Cell Lymphoma, T-Cell, Cutaneous Lymphoma, Large-Cell, Anaplastic Lymphoma, B-Cell, Marginal Zone Lymphoma, Extranodal NK-T-Cell Lymphoma, Mantle-Cell Epstein-Barr Virus Infections Herpesviridae Infections DNA Virus Infections Virus Diseases Tumor Virus Infections Neoplasms by Histologic Type |
ClinicalTrials.gov processed this record on May 23, 2013