Randomized Trial of G-CSF Alone Versus Intermediate-dose Ara-C Plus G-CSF Mobilization in Multiple Myeloma Patients.

NCT01908621 | Completed Phase 3 DMC

• 1 other identifier: MMMobil-COI-01
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Myeloma

Keywords

multiple myeloma; mobilization; G-CSF; filgrastim; cytosine arabinoside; autologous stem cell transplantation

Outcome Measures

Primary Outcomes (1)

• The proportion of patients with stem cell yield at least 5 × 10^6 CD34+ cells/kg in each treatment arm.

  After up to three leukaphereses (7-20 days after starting mobilization regimen).

Secondary Outcomes (8)

• 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 leukaphereses needed to harvest target amount of stem cells.

  7-20 days after starting mobilization regimen.

• 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

Study Arms (2)

G-CSF (filgrastim)

ACTIVE COMPARATOR

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.

Drug: G-CSF (filgrastim)

Cytosine arabinoside + G-CSF (filgrastim)

ACTIVE COMPARATOR

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.

Drug: Cytosine arabinoside + G-CSF (filgrastim)

Interventions

G-CSF (filgrastim) DRUG

G-CSF (filgrastim)

Cytosine arabinoside + G-CSF (filgrastim) DRUG

Cytosine arabinoside + G-CSF (filgrastim)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 0-1.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Maria Sklodowska-Curie National Research Institute of Oncology: lead

Study Sites (1)

Department of Bone Marrow Transplantation and Oncohematology, Maria Sklodowska-Curie Institute, Oncology Center, Gliwice Branch

Gliwice, 44-101, Poland

Location

Related Publications (5)

• 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.

  PMID: 11567990 BACKGROUND

• 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.

  PMID: 15273706 BACKGROUND

• 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.

  PMID: 22261379 BACKGROUND

• 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.

  PMID: 22797877 BACKGROUND

• 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.

  PMID: 23292239 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Granulocyte Colony-Stimulating Factor; Filgrastim; Cytarabine

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Tomasz Czerw, MD

  Maria Sklodowska-Curie Institute, Oncology Center, Gliwice Branch, Wybrzeze Armii Krajowej 15 Street, 44-101 Gliwice, Poland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2013
• First Posted: July 25, 2013
• Study Start: March 20, 2013
• Primary Completion: March 18, 2016
• Study Completion: October 27, 2017
• Last Updated: August 28, 2018

Record last verified: 2018-07

Locations

PL (1)