Back to resultsRandomized Trial of G-CSF Alone Versus Intermediate-dose Ara-C Plus G-CSF Mobilization in Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma
Primary Purpose
Hodgkin's Lymphoma, Non-Hodgkin's Lymphoma
Status
Unknown status
Phase
Phase 3
Locations
Poland
Study Type
Interventional
Intervention
G-CSF (filgrastim)
Cytosine arabinoside with G-CSF (filgrastim)
Sponsored by
About this trial
This is an interventional treatment trial for Hodgkin's Lymphoma focused on measuring Hodgkin's lymphoma, Non-Hodgkin's lymphoma, mobilization, G-CSF, filgrastim, cytosine arabinoside, autologous stem cell transplantation
Eligibility Criteria
Inclusion Criteria:
- Hodgkin's lymphoma and non-Hodgkin's lymphoma patients considered eligible for autologous stem cell transplantation procedure.
- Must not have achieved complete remission after first line of therapy or must have relapsed lymphoma.
- Must have received at least two lines of therapy including four or more cycles.
- Must have achieved a partial (PR) or complete remission (CR) .
- Must be 18-65 years of age.
- Must have World Health Organization performance status 0-1.
- Time from administration or discontinuation of any chemotherapy agent must be at least four weeks.
- Hemoglobin level > 8 g/dl, Absolute neutrophil count (ANC) > 1.5 x 10^9/L, Platelet count >100 x 10^9/L.
- Serum creatinine < 1.5 x upper limit of normal (ULN), serum bilirubin < 1.5 ULN, serum aspartate transaminase (AST/SGOT) < 2.5 x ULN, serum alanine transaminase (ALT/SGPT) < 2.5 x ULN.
- Negative human immunodeficiency virus (HIV) infection test.
- Negative pregnancy test.
- Must understand and voluntarily sign informed consent form.
Exclusion Criteria:
- Failure of prior, first-line mobilization regimen.
- Infiltration of central nervous system.
- Bone marrow plasma cell infiltration of above 20%.
- Administration of nitrosourea derivatives (Carmustine, Lomustine) within 4 weeks before starting study treatment.
- Administration of growth-factor other than G-CSF Administration of G-CSF within 14 days before starting study treatment.
- Ongoing or active infection.
- Coexisting neoplasm, other than Hodgkin's or non-Hodgkin's lymphoma.
- Administration of radioimmunotherapy in past.
- Pregnant or lactating females.
- Patients treated with use of autologous or allogenic stem cell transplantation in the past.
- Positive human immunodeficiency virus (HIV) infection test.
Sites / Locations
- Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice BranchRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
G-CSF (filgrastim)
Cytosine arabinoside + G-CSF (filgrastim)
Arm Description
1.G-CSF at 10 μg/kg per day (divided into two doses every 12 hours) subcutaneously for up to 7 days.
Cytosine arabinoside will be administered as a 2-hour i.v. infusion at a dose of 0.4 g/m2 twice daily on days 1 and 2 (total dose 1.6 g/m2). G-CSF 5-10 μg/kg per day (divided into two doses every 12 hours) will be started on day 5 subcutaneously and continued until last leukapheresis.
Outcomes
Primary Outcome Measures
• The proportion of patients with stem cell yield at least 2 × 10^6 CD34+ cells/kg in each treatment arm.
Secondary Outcome Measures
Peak level of CD34+ cells in peripheral blood (cells/μl).
Total number of harvested CD34+cells/kg.
Number of leukaphereses needed to harvest target amount of stem cells.
The proportion of hematologic and non-hematologic complications.
Duration of neutropenia < 0.5 x10^9/L.
Number of blood transfusions needed.
Duration of hospital stay.
Time of neutrophil and platelet engraftment after autologous stem cel transplantation.
Duration of thrombocytopenia <50 x 10 ^9/L.
Number of days of antibiotics therapy.
Full Information
NCT ID
NCT02722733
First Posted
March 11, 2016
Last Updated
March 24, 2016
Sponsor
Maria Sklodowska-Curie National Research Institute of Oncology
1. Study Identification
Unique Protocol Identification Number
NCT02722733
Brief Title
Randomized Trial of G-CSF Alone Versus Intermediate-dose Ara-C Plus G-CSF Mobilization in Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma
Official Title
Safety and Efficacy of Stem Cell Mobilization Using G-CSF (Filgrastim) Alone Compared to Intermediate-dose Cytosine Arabinoside Plus G-CSF in Hodgkin's Lymphoma and Non-Hodgkin's Lymphoma Patients.
Study Type
Interventional
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Unknown status
Study Start Date
March 2016 (undefined)
Primary Completion Date
March 2017 (Anticipated)
Study Completion Date
April 2017 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Maria Sklodowska-Curie National Research Institute of Oncology
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of the study is to compare safety and efficacy of stem cell mobilization using G-CSF (filgrastim) alone vs. intermediate-dose cytosine arabinoside plus G-CSF in Hodgkin's lymphoma and non-Hodgkin's lymphoma patients.
Detailed Description
Autologous hematopoietic stem cell transplantation (autoHSCT) is a standard treatment of eligible patients suffering from Hodgkin's Lymphoma or non-Hodgkin's Lymphoma (HL, NHL). AutoHSCT allows to further improve results of the therapy. Nowadays, 99% of the procedures are performed using peripheral blood as a source of stem cells. Hence, the crucial point is to harvest adequate number of stem cells allowing hematopoietic recovery. The number of 2 × 10^6 CD34+ cells/kg is considered the minimal level in autoHSCT. There are two main mobilization strategies being used: based on G-CSF alone or in combination with chemotherapy (cyclophosphamide (CY) at dose range 1.6 g/m2 is mainly used in HL and NHL setting). However, a proportion of patients (5-40%) fail to collect the minimum number of cells required. Novel agents, like plerixafor, CXCR4 inhibitor, may enable effective CD34+ cell harvest in "poor mobilizers". Nevertheless, the optimal first-line and cost-effective protocol for mobilization of hematopoietic stem cells has not been determined so far.
Randomized trials compare chemomobilization with the use of CY + G-CSF to G-CSF alone, which had been conducted so far, did not demonstrate clear advantage of addition of CY to the growth factor. Intermediate-dose cytosine arabinoside (AraC), 1.6 g/m2 plus filgrastim, has been shown to produce very high efficacy as a first or second-line mobilization regimen in patients with lymphoid malignancies. In a retrospective comparison, this strategy was significantly more effective than CY + G-CSF. This suggest that the type of chemotherapy agent added to G-CSF may play role in mobilization efficacy and that the combination of AraC and G-CSF may be more effective than G-CSF used alone. The goal of current study is to verify this hypothesis in randomized controlled trial.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hodgkin's Lymphoma, Non-Hodgkin's Lymphoma
Keywords
Hodgkin's lymphoma, Non-Hodgkin's lymphoma, mobilization, G-CSF, filgrastim, cytosine arabinoside, autologous stem cell transplantation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
90 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
G-CSF (filgrastim)
Arm Type
Active Comparator
Arm Description
1.G-CSF at 10 μg/kg per day (divided into two doses every 12 hours) subcutaneously for up to 7 days.
Arm Title
Cytosine arabinoside + G-CSF (filgrastim)
Arm Type
Active Comparator
Arm Description
Cytosine arabinoside will be administered as a 2-hour i.v. infusion at a dose of 0.4 g/m2 twice daily on days 1 and 2 (total dose 1.6 g/m2).
G-CSF 5-10 μg/kg per day (divided into two doses every 12 hours) will be started on day 5 subcutaneously and continued until last leukapheresis.
Intervention Type
Drug
Intervention Name(s)
G-CSF (filgrastim)
Intervention Type
Drug
Intervention Name(s)
Cytosine arabinoside with G-CSF (filgrastim)
Primary Outcome Measure Information:
Title
• The proportion of patients with stem cell yield at least 2 × 10^6 CD34+ cells/kg in each treatment arm.
Time Frame
After up to three leukaphereses (7-20 days after starting mobilization regimen).
Secondary Outcome Measure Information:
Title
Peak level of CD34+ cells in peripheral blood (cells/μl).
Time Frame
7-20 days after starting mobilization regimen.
Title
Total number of harvested CD34+cells/kg.
Time Frame
After up to three leukaphereses (7-20 days after starting mobilization regimen).
Title
Number of leukaphereses needed to harvest target amount of stem cells.
Time Frame
7-20 days after starting mobilization regimen.
Title
The proportion of hematologic and non-hematologic complications.
Time Frame
1 month after transplantation.
Title
Duration of neutropenia < 0.5 x10^9/L.
Time Frame
1 month after transplantation.
Title
Number of blood transfusions needed.
Time Frame
1 month after transplantation.
Title
Duration of hospital stay.
Time Frame
1 month after transplantation.
Title
Time of neutrophil and platelet engraftment after autologous stem cel transplantation.
Time Frame
1 month after transplantation.
Title
Duration of thrombocytopenia <50 x 10 ^9/L.
Time Frame
1 month after transplantation.
Title
Number of days of antibiotics therapy.
Time Frame
1 month after transplantation
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Hodgkin's lymphoma and non-Hodgkin's lymphoma patients considered eligible for autologous stem cell transplantation procedure.
Must not have achieved complete remission after first line of therapy or must have relapsed lymphoma.
Must have received at least two lines of therapy including four or more cycles.
Must have achieved a partial (PR) or complete remission (CR) .
Must be 18-65 years of age.
Must have World Health Organization performance status 0-1.
Time from administration or discontinuation of any chemotherapy agent must be at least four weeks.
Hemoglobin level > 8 g/dl, Absolute neutrophil count (ANC) > 1.5 x 10^9/L, Platelet count >100 x 10^9/L.
Serum creatinine < 1.5 x upper limit of normal (ULN), serum bilirubin < 1.5 ULN, serum aspartate transaminase (AST/SGOT) < 2.5 x ULN, serum alanine transaminase (ALT/SGPT) < 2.5 x ULN.
Negative human immunodeficiency virus (HIV) infection test.
Negative pregnancy test.
Must understand and voluntarily sign informed consent form.
Exclusion Criteria:
Failure of prior, first-line mobilization regimen.
Infiltration of central nervous system.
Bone marrow plasma cell infiltration of above 20%.
Administration of nitrosourea derivatives (Carmustine, Lomustine) within 4 weeks before starting study treatment.
Administration of growth-factor other than G-CSF Administration of G-CSF within 14 days before starting study treatment.
Ongoing or active infection.
Coexisting neoplasm, other than Hodgkin's or non-Hodgkin's lymphoma.
Administration of radioimmunotherapy in past.
Pregnant or lactating females.
Patients treated with use of autologous or allogenic stem cell transplantation in the past.
Positive human immunodeficiency virus (HIV) infection test.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Katarzyna Soska, MD
Phone
+48322788520
Email
katarzyna.soska@io.gliwice.pl
Facility Information:
Facility Name
Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch
City
Gliwice
ZIP/Postal Code
44-101
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sebastian Giebel, Prof MD
Phone
+48322788523
Email
ots@gliwice.io.pl
First Name & Middle Initial & Last Name & Degree
Katarzyna Soska, MD
12. IPD Sharing Statement
Citations:
PubMed Identifier
11567990
Citation
Narayanasami U, Kanteti R, Morelli J, Klekar A, Al-Olama A, Keating C, O'Connor C, Berkman E, Erban JK, Sprague KA, Miller KB, Schenkein DP. Randomized trial of filgrastim versus chemotherapy and filgrastim mobilization of hematopoietic progenitor cells for rescue in autologous transplantation. Blood. 2001 Oct 1;98(7):2059-64. doi: 10.1182/blood.v98.7.2059.
Results Reference
background
PubMed Identifier
15273706
Citation
Karanth M, Chakrabarti S, Lovell RA, Harvey C, Holder K, McConkey CC, McDonald D, Fegan CD, Milligan DW. A randomised study comparing peripheral blood progenitor mobilisation using intermediate-dose cyclophosphamide plus lenograstim with lenograstim alone. Bone Marrow Transplant. 2004 Sep;34(5):399-403. doi: 10.1038/sj.bmt.1704598.
Results Reference
background
PubMed Identifier
22261379
Citation
Sheppard D, Bredeson C, Allan D, Tay J. Systematic review of randomized controlled trials of hematopoietic stem cell mobilization strategies for autologous transplantation for hematologic malignancies. Biol Blood Marrow Transplant. 2012 Aug;18(8):1191-203. doi: 10.1016/j.bbmt.2012.01.008. Epub 2012 Jan 16.
Results Reference
background
PubMed Identifier
22797877
Citation
Kruzel T, Sadus-Wojciechowska M, Najda J, Czerw T, Glowala-Kosinska M, Holowiecki J, Giebel S. Very high efficacy of intermediate-dose cytarabine in combination with G-CSF as a second-line mobilization of hematopoietic stem cells. Int J Hematol. 2012 Aug;96(2):287-9. doi: 10.1007/s12185-012-1135-5. Epub 2012 Jul 14. No abstract available.
Results Reference
background
PubMed Identifier
23292239
Citation
Giebel S, Kruzel T, Czerw T, Sadus-Wojciechowska M, Najda J, Chmielowska E, Grosicki S, Jurczyszyn A, Pasiarski M, Nowara E, Glowala-Kosinka M, Chwieduk A, Mitrus I, Smagur A, Holowiecki J. Intermediate-dose Ara-C plus G-CSF for stem cell mobilization in patients with lymphoid malignancies, including predicted poor mobilizers. Bone Marrow Transplant. 2013 Jul;48(7):915-21. doi: 10.1038/bmt.2012.269. Epub 2013 Jan 7.
Results Reference
background
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Randomized Trial of G-CSF Alone Versus Intermediate-dose Ara-C Plus G-CSF Mobilization in Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma
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