Bendamustine Hydrochloride, Etoposide, Dexamethasone, and Filgrastim For Peripheral Blood Stem Cell Mobilization in Treating Patients With Refractory or Recurrent Lymphoma or Multiple Myeloma
Primary Purpose
Adult Nasal Type Extranodal NK/T-cell Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
bendamustine hydrochloride
dexamethasone
filgrastim
leukapheresis
laboratory biomarker analysis
flow cytometry
etoposide
Sponsored by
About this trial
This is an interventional treatment trial for Adult Nasal Type Extranodal NK/T-cell Lymphoma
Eligibility Criteria
Inclusion Criteria:
- Patients must have relapsed or primary refractory lymphoid malignancy (including B-cell, T-cell, or Hodgkin lymphoma), or multiple myeloma; other transplant eligible diagnoses (e.g. germ cell tumor) can be included with principal investigator (PI) approval
- World Health Organization (WHO) classification of patients' malignancies must be provided
- Patients with lymphoid malignancies must have a computed tomography (CT) of chest, abdomen, and pelvis within six weeks of enrollment; patients with evidence of lymphadenopathy in the neck must have a CT of neck
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Absolute neutrophil count (ANC) >= 1,500/mm^3
- Platelets >= 100,000/mm^3 (without transfusion or growth factor support)
- Creatinine clearance (CrCl) greater than 50/ml per minute (all tests must be performed within 28 days prior to registration)
- Total bilirubin < 1.5 times upper limit of normal
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 times upper limit of normal
- All patients must be informed of the investigational nature of this study and have given written consent in accordance with institutional and federal guidelines
- Adequate venous access plan in place for apheresis procedure
- Three or fewer prior myelotoxic treatment regimens (specific regimens include ifosfamide, carboplatin and etoposide [ICE]; cisplatin, cytarabine, and dexamethasone [DHAP]; methotrexate [MTX]/high-dose cytarabine [HiDAC]; cyclophosphamide, vincristine, doxorubicin, and dexamethasone [hyperCVAD]; bortezomib, thalidomide, dexamethasone and 4-day continuous infusions of cisplatin, doxorubicin, cyclophosphamide, and etoposide [VTD-PACE])
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
- Greater than six prior cycles of lenalidomide therapy
- Patients who have previously demonstrated resistance to bendamustine therapy (i.e. no response or progression w/in 6 months)
- Fludarabine or other nucleoside analog (except gemcitabine or cytarabine) therapy within 24 months of registration; patients with limited exposure to fludarabine/other nucleoside analog therapy within 24 months may be considered eligible with review and approval by the PI or Co-PI prior to study entry
- Symptomatic cardiopulmonary disease
- Prior autologous or allogeneic transplantation
- Prior radioimmunotherapy within 12 weeks of registration
- Prior failed (< 5 x 10^6 CD34/kg) PBSC collection due to inability to mobilize stem cells
- Prior pelvic or spinal irradiation
- Previous systemic chemotherapy/immunotherapy within 3 weeks before study entry
- Concurrent use of other anti-cancer agents or experimental treatments
- Known allergy or intolerance to bendamustine, mannitol, GCSF or dexamethasone
- More than 3 cycles of myelotoxic salvage chemotherapy within the past 4 months (specific regimens include ICE, DHAP, MTX/HiDAC, hyperCVAD, VTD-PACE)
Sites / Locations
- Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (chemotherapy and colony-stimulating factor)
Arm Description
Patients receive bendamustine hydrochloride IV over 30-60 minutes on days 1 and 2, etoposide IV over 60-240 minutes on days 1-3, dexamethasone PO on days 1-4, and filgrastim SC beginning on day 5 and continuing until peripheral blood stem cell collection is complete. Patients undergo leukapheresis daily for a minimum of 3 days or until > 5 x 10^6 CD34+/kg has been collected. .
Outcomes
Primary Outcome Measures
Successful Mobilization and Collection of PBSCs
Count of participants with successful mobilization and collection of PBSCs. Defined as collection of > 2 x 10^6 CD34/kg. The current study will be deemed to be potentially efficacious if the observed rate of success is at least 80%.
Secondary Outcome Measures
Full Information
NCT ID
NCT01110135
First Posted
April 20, 2010
Last Updated
April 14, 2017
Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT01110135
Brief Title
Bendamustine Hydrochloride, Etoposide, Dexamethasone, and Filgrastim For Peripheral Blood Stem Cell Mobilization in Treating Patients With Refractory or Recurrent Lymphoma or Multiple Myeloma
Official Title
A Phase II Study of Bendamustine (B), Etoposide (E), Dexamethasone (D), and GCSF for Peripheral Blood Hematopoietic Stem Cell Mobilization (BED)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
August 2010 (undefined)
Primary Completion Date
November 2013 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This phase II trial is studying how well giving bendamustine hydrochloride, etoposide, dexamethasone, and filgrastim together for peripheral stem cell mobilization works in treating patients with refractory or recurrent lymphoma or multiple myeloma. Giving chemotherapy, such as bendamustine hydrochloride, etoposide, and dexamethasone, before a peripheral stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as filgrastim, and certain chemotherapy drugs helps stem cells move from the bone marrow to the blood so they can be collected and stored
Detailed Description
PRIMARY OBJECTIVES:
I. To estimate the frequency of bendamustine (bendamustine hydrochloride) combined with GCSF (filgrastim) and dexamethasone to successfully mobilize peripheral blood stem cells (PBSCs) (as determined by collecting a minimum of 2 x 10^6 cluster of differentiation (CD)34+/kg).
SECONDARY OBJECTIVES:
I. To evaluate the response rate to bendamustine by diagnosis using established disease-specific response criteria.
II. To examine the number of apheresis cycles required to collect a minimum of 2 x 10^6 CD34+ cells/kg and ideally >= 5 x 10^6 CD34+ cells/kg (when achievable).
III. To assess the impact of bendamustine on B and T-lymphocyte populations in the peripheral blood (CD20+ cells, natural killer [NK] cells, CD4+25+ foxP3- regulatory cells, and CD8 cells).
OUTLINE:
Patients receive bendamustine hydrochloride intravenously (IV) over 30-60 minutes on days 1 and 2, etoposide IV over 60-240 minutes on days 1-3, dexamethasone orally (PO) on days 1-4, and filgrastim subcutaneously (SC) beginning on day 5 and continuing until peripheral blood stem cell collection is complete. Patients undergo leukapheresis daily for a minimum of 3 days or until > 5 x 10^6 CD34+/kg has been collected.
After completion of study treatment, patients are followed for up to 5 years.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Nasal Type Extranodal NK/T-cell Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell 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, Peripheral T-cell 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 Adult T-cell Leukemia/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, Refractory Multiple Myeloma, Small Intestine Lymphoma, Splenic Marginal Zone Lymphoma, Waldenström Macroglobulinemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
43 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment (chemotherapy and colony-stimulating factor)
Arm Type
Experimental
Arm Description
Patients receive bendamustine hydrochloride IV over 30-60 minutes on days 1 and 2, etoposide IV over 60-240 minutes on days 1-3, dexamethasone PO on days 1-4, and filgrastim SC beginning on day 5 and continuing until peripheral blood stem cell collection is complete. Patients undergo leukapheresis daily for a minimum of 3 days or until > 5 x 10^6 CD34+/kg has been collected.
.
Intervention Type
Drug
Intervention Name(s)
bendamustine hydrochloride
Other Intervention Name(s)
bendamustin hydrochloride, bendamustine, cytostasan hydrochloride, Treanda
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
dexamethasone
Other Intervention Name(s)
Aeroseb-Dex, Decaderm, Decadron, DM, DXM
Intervention Description
Given PO
Intervention Type
Biological
Intervention Name(s)
filgrastim
Other Intervention Name(s)
G-CSF, Neupogen
Intervention Description
Given SC
Intervention Type
Procedure
Intervention Name(s)
leukapheresis
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
flow cytometry
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
etoposide
Other Intervention Name(s)
EPEG, VP-16, VP-16-213
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Successful Mobilization and Collection of PBSCs
Description
Count of participants with successful mobilization and collection of PBSCs. Defined as collection of > 2 x 10^6 CD34/kg. The current study will be deemed to be potentially efficacious if the observed rate of success is at least 80%.
Time Frame
Within 7 days of apheresis and within 6 weeks of receiving bendamustine hydrochloride
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients must have relapsed or primary refractory lymphoid malignancy (including B-cell, T-cell, or Hodgkin lymphoma), or multiple myeloma; other transplant eligible diagnoses (e.g. germ cell tumor) can be included with principal investigator (PI) approval
World Health Organization (WHO) classification of patients' malignancies must be provided
Patients with lymphoid malignancies must have a computed tomography (CT) of chest, abdomen, and pelvis within six weeks of enrollment; patients with evidence of lymphadenopathy in the neck must have a CT of neck
Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Absolute neutrophil count (ANC) >= 1,500/mm^3
Platelets >= 100,000/mm^3 (without transfusion or growth factor support)
Creatinine clearance (CrCl) greater than 50/ml per minute (all tests must be performed within 28 days prior to registration)
Total bilirubin < 1.5 times upper limit of normal
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 times upper limit of normal
All patients must be informed of the investigational nature of this study and have given written consent in accordance with institutional and federal guidelines
Adequate venous access plan in place for apheresis procedure
Three or fewer prior myelotoxic treatment regimens (specific regimens include ifosfamide, carboplatin and etoposide [ICE]; cisplatin, cytarabine, and dexamethasone [DHAP]; methotrexate [MTX]/high-dose cytarabine [HiDAC]; cyclophosphamide, vincristine, doxorubicin, and dexamethasone [hyperCVAD]; bortezomib, thalidomide, dexamethasone and 4-day continuous infusions of cisplatin, doxorubicin, cyclophosphamide, and etoposide [VTD-PACE])
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
Greater than six prior cycles of lenalidomide therapy
Patients who have previously demonstrated resistance to bendamustine therapy (i.e. no response or progression w/in 6 months)
Fludarabine or other nucleoside analog (except gemcitabine or cytarabine) therapy within 24 months of registration; patients with limited exposure to fludarabine/other nucleoside analog therapy within 24 months may be considered eligible with review and approval by the PI or Co-PI prior to study entry
Symptomatic cardiopulmonary disease
Prior autologous or allogeneic transplantation
Prior radioimmunotherapy within 12 weeks of registration
Prior failed (< 5 x 10^6 CD34/kg) PBSC collection due to inability to mobilize stem cells
Prior pelvic or spinal irradiation
Previous systemic chemotherapy/immunotherapy within 3 weeks before study entry
Concurrent use of other anti-cancer agents or experimental treatments
Known allergy or intolerance to bendamustine, mannitol, GCSF or dexamethasone
More than 3 cycles of myelotoxic salvage chemotherapy within the past 4 months (specific regimens include ICE, DHAP, MTX/HiDAC, hyperCVAD, VTD-PACE)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ajay Gopal
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Bendamustine Hydrochloride, Etoposide, Dexamethasone, and Filgrastim For Peripheral Blood Stem Cell Mobilization in Treating Patients With Refractory or Recurrent Lymphoma or Multiple Myeloma
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