Clinical trial NCT01908621: Randomized Trial of G-CSF Alone Versus Intermediate-dose Ara-C Plus G-CSF Mobilization in Multiple Myeloma Patients.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: multiple myeloma
mobilization
G-CSF
filgrastim
cytosine arabinoside
autologous stem cell transplantation
Lead sponsor: Maria Sklodowska-Curie National Research Institute of Oncology
Sponsor class: OTHER
First posted: 2013-07-25
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Multiple myeloma patients considered eligible for tandem autologous stm cell transplantation procedure.
2. Must have received at least one line of therapy including six or more cycles containing components like thalidomide, bortezomib, lenalidomide or melphalan.
3. Must have achieved a partial remission (PR) or better response as assessed by International Myeloma Working Group guidelines.
4. Must be 18-65 years of age.
5. Must have World Health Organization performance status 0-1.
6. Time form discontinuation of administration of any chemotherapy agent must be at least four weeks and immunomodulatory drug at least seven days.
7. Hemoglobin level \> 8 g/dl, Absolute neutrophil count (ANC) \> 1.5 x 109/L, Platelet count \>100 x 109/L.
8. 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.
9. Negative human immunodeficiency virus (HIV) infection test.
10. Negative pregnancy test.
11. Must understand and voluntarily sign informed consent form.

Exclusion Criteria:

1. Failure of prior, first-line mobilization regimen.
2. Bone marrow plasma cell infiltration of above 20%.
3. Administration of growth-factor other than G-CSF within 4 weeks before starting study treatment.
4. Administration of G-CSF within 14 days before starting study treatment.
5. Ongoing or active infection.
6. Coexisting neoplasm, other than multiple myeloma.
7. Pregnant or lactating females.
8. Patients treated with use of autologous or allogenic stem cell transplantation in the past.
9. Positive human immunodeficiency virus (HIV) infection test.

Primary outcomes:
measure: The proportion of patients with stem cell yield at least 5 × 10^6 CD34+ cells/kg in each treatment arm.
timeFrame: After up to three leukaphereses (7-20 days after starting mobilization regimen).
Secondary outcomes:
measure: Peak level of CD34+ cells in peripheral blood (/μl).
timeFrame: 7-20 days after starting mobilization regimen.
measure: Total number of harvested CD34+cells/kg.
timeFrame: Ater up to three leukaphereses (7-20 days after starting mobilization regimen).
measure: Number of leukaphereses needed to harvest target amount of stem cells.
timeFrame: 7-20 days after starting mobilization regimen.
measure: The proportion of hematologic and non-hematologic complications.
timeFrame: 1 month
measure: Duration of neutropenia < 0.5 x10^9/L and thrombocytopenia <50 x10^9/L.
timeFrame: 1 month
measure: Number of blood transfusions needed and number of days of antibiotics therapy.
timeFrame: 1 month
measure: Duration of hospital stay.
timeFrame: 1 month
measure: Time of neutrophil and platelet engraftment after autologous stem cel transplantation.
timeFrame: 1 month
Other outcomes:
Locations:
city: Gliwice
country: Poland
facility: Department of Bone Marrow Transplantation and Oncohematology, Maria Sklodowska-Curie Institute, Oncology Center, Gliwice Branch
Study officials:
affiliation: Maria Sklodowska-Curie Institute, Oncology Center, Gliwice Branch, Wybrzeze Armii Krajowej 15 Street, 44-101 Gliwice, Poland
name: Tomasz Czerw, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.