Safety and Efficacy of Stem Cell Mobilization Using G-CSF (Filgrastim) Alone Compared to Intermediate-dose Cytosine Arabinoside Plus G-CSF in Multiple Myeloma Patients.
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Enrollment
- 90
- Locations
- 1
- Primary Endpoint
- The proportion of patients with stem cell yield at least 5 × 10^6 CD34+ cells/kg in each treatment arm.
Study Overview
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 multiple myeloma patients.
Detailed Description
Autologous hematopoietic stem cell transplantation (autoHSCT) is a standard treatment of eligible patients suffering from multiple myeloma (MM). Tandem 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 5 × 10^6 CD34+ cells/kg is considered the optimal level, as far as double autoHSCT is concerned. There are two main mobilization strategies being used: based on G-CSF alone or in combination with chemotherapy (cyclophosphamide (CY) at dose range 1.5-7 g/m2 is mainly used in MM 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 comparing chemomobilization with 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 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, including MM. In a retrospective comparison, this strategy was significantly more effective than CY + filgrastim. 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Multiple myeloma patients considered eligible for tandem autologous stm cell transplantation procedure.
- •Must have received at least one line of therapy including six or more cycles containing components like thalidomide, bortezomib, lenalidomide or melphalan.
- •Must have achieved a partial remission (PR) or better response as assessed by International Myeloma Working Group guidelines.
- •Must be 18-65 years of age.
- •Must have World Health Organization performance status 0-
- •Time form discontinuation of administration of any chemotherapy agent must be at least four weeks and immunomodulatory drug at least seven days.
- •Hemoglobin level > 8 g/dl, Absolute neutrophil count (ANC) > 1.5 x 109/L, Platelet count >100 x 109/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.
- •Bone marrow plasma cell infiltration of above 20%.
- •Administration of growth-factor other than G-CSF within 4 weeks before starting study treatment.
- •Administration of G-CSF within 14 days before starting study treatment.
- •Ongoing or active infection.
- •Coexisting neoplasm, other than multiple myeloma.
- •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.
Arms & Interventions
G-CSF (filgrastim)
Patients will receive G-CSF(filgrastim) at 10 μg/kg per day (divided into two doses every 12 hours) subcutaneously for up to 7 days. On day 5, circulating CD34+ level will be determined. Leukapheresis will be started when the CD34+ blood level will reach at least 10/µl. If the level will be not achieved, G-CSF administration will be continued until CD34+ level will decrease compared to the preceding day. Leukaphereses will be performed using Spectra-Optia Apheresis System (TherumoBCT Inc, Lakewood, CO, USA) according to the manufacturers protocols for mononuclear cell harvesting, processing 2 total blood volumes. In case of failing to harvest targeted number of stem cells (5 × 10^6 CD34+ cells/kg), next leukapheresis can be performed on following two days (maximum 3 leukaphereses) if circulating CD34+ cell level will remain as described above.
Intervention: G-CSF (filgrastim) (Drug)
Cytosine arabinoside + G-CSF (filgrastim)
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 (filgrastim) 5-10 ug/kg will be started on day 5 and continued until last leukapheresis. The number of circulating CD34+ cells will be first evaluated after neutrophil recovery from nadir. Leukapheresis will be started when the CD34+ blood level will reach at least 10/µl. If the level will be not achieved, G-CSF administration will be continued until CD34+ level will decrease. Leukaphereses will be performed using Spectra-Optia Apheresis System (TherumoBCT Inc, Lakewood, CO, USA) according to the manufacturers protocols for mononuclear cell harvesting, processing 2 total blood volumes. In case of failing to harvest targeted number of stem cells (5 × 10^6 CD34+ cells/kg), next leukapheresis can be performed on following two days (maximum 3 leukaphereses) if circulating CD34+ cell level will remain as described above.
Intervention: Cytosine arabinoside + G-CSF (filgrastim) (Drug)
Outcomes
Primary Outcomes
The proportion of patients with stem cell yield at least 5 × 10^6 CD34+ cells/kg in each treatment arm.
Time Frame: After up to three leukaphereses (7-20 days after starting mobilization regimen).
Secondary Outcomes
- Number of leukaphereses needed to harvest target amount of stem cells.(7-20 days after starting mobilization regimen.)
- Duration of hospital stay.(1 month)
- The proportion of hematologic and non-hematologic complications.(1 month)
- Duration of neutropenia < 0.5 x10^9/L and thrombocytopenia <50 x10^9/L.(1 month)
- Peak level of CD34+ cells in peripheral blood (/μl).(7-20 days after starting mobilization regimen.)
- Total number of harvested CD34+cells/kg.(Ater up to three leukaphereses (7-20 days after starting mobilization regimen).)
- Number of blood transfusions needed and number of days of antibiotics therapy.(1 month)
- Time of neutrophil and platelet engraftment after autologous stem cel transplantation.(1 month)