PAV-trial: Plerixafor and Chemotherapy With Vinorelbine for Stem Cell Mobilization in Patients With Myeloma. A Pilot Phase II Study.
18 Years
70 Years
Both
Myeloma
Trial Information
PAV-trial: Plerixafor and Chemotherapy With Vinorelbine for Stem Cell Mobilization in Patients With Myeloma. A Pilot Phase II Study.
Background
High-dose chemotherapy with autologous stem cell support is the current standard procedure
in the first-line treatment in younger patients with myeloma fit for intensive treatment.
Current practice in Switzerland for stem cell mobilization is the combination of
chemotherapy and G-CSF stimulation in myeloma patients fit for high-dose chemotherapy with
melphalan and autologous stem cell transplant. For mobilization chemotherapy, a single dose
of vinorelbine is commonly used, producing mild myelosuppression. G-CSF is started at day 4
on a daily basis, allowing stem cell apheresis usually at day 8. In a subsequent study, we
evaluated the use of pegylated G-CSF given as a single injection at day 4 together with
vinorelbine. We found this regimen equally feasible, reliable and allowing collection of
stem cells in an equally high percentage. In the current proposal, we suggest to continue
this line of research investigating the mobilization using chemotherapy with vinorelbine. We
propose to study the feasibility of this mobilization chemotherapy in the absence of growth
factors, thus without G-CSF, in combination with Plerixafor.
Objective
Primary objective: To assess the feasibility of collection of > 6 million CD34+ peripheral
blood stem cells/kg body weight in 2 days.
Secondary objectives: Assessment of safety of plerixafor during mobilization and collection
of peripheral blood stem cells; feasibility of intravenous plerixafor application and stem
cell apheresis in a one-day procedure on an ambulatory basis; evaluation of engraftment of
peripheral blood stem cells mobilized by vinorelbine and plerixafor; evaluation of the costs
for mobilization with plerixafor.
Methods
Chemotherapy with vinorelbine is given at a standard dose at day 1, on an ambulatory basis.
In part A (10 patients), G-CSF is given s.c., divided in two daily doses starting at day 4
until collection of stem cells. Plerixafor is given as an i.v. application on day 8 in the
dose of 240 microg/kg b.w. Stem cell collection is initiated 4 hours later at day 8, if at
least 20 x 103 of CD34+ cells / ml peripheral blood are detected. In case of insufficient
collection, the procedure is repeated at day 9, including repetition of plerixafor
application.
Part B (30 patients): If the combination of plerixafor and vinorelbine is found feasible and
in the absence of unexpected toxicity, additional 30 patients will be studied in part B of
this study. No G-CSF will be administered in part B, otherwise the treatment plan is as it
is in part A.
High dose Melphalan will be used as conditioning regimen. After transplantation, G-CSF will
be given to subjects starting at day +5 after PBPC reinfusion.
Inclusion Criteria:
- Symptomatic stage I or stage II and III myeloma patients after standard first-line
non-melphalan containing induction treatment. Patients must be fit for subsequent
consolidation with high-dose chemotherapy with melphalan with autologous stem cell
support.
- Standard induction chemotherapy comprises regimens including thalidomide, bortezomib,
or lenalidomide (up to 4 cycles), alone or in combination with dexamethasone.
Combinations of novel agents are allowed as well as induction with the VAD regimen.
- Patients must have achieved at least a partial response according to the Bladé
criteria after induction chemotherapy.
- Patient must be aged 18-70 years, with an ECOG < 2 and has given voluntary written
informed consent.
- Platelets count 50 x 109/l without transfusion support within 7 days before the
laboratory test.
- Absolute neutrophil count (ANC) 1.0 x 109/l without the use of colony stimulating
factors.
- Corrected serum calcium < 3 mmol/L.
- Aspartate transaminase (AST) <= 1.5 x ULN.
- Alanine transaminase (ALT) <= 1.5 x ULN.
- Total bilirubin <= 2 x ULN.
- Creatinin-clearance >= 50 ml/min.
- Negative pregnancy test within 14 days prior to registration for all women of
childbearing potential. Patients of childbearing potential must implement adequate
measures to avoid pregnancy during study treatment and for additional 12 months. No
pregnant or lactating patients are allowed.
Exclusion Criteria
- Patients previously treated with melphalan or extensive radiotherapy to the bone
marrow.
- Patients with more than 4 cycles of chemotherapy with Lenalidomide.
- Patients not fit for autologous stem cell transplantation.
- Patient receiving colony stimulating factors.
- Patient underwent plasmaphereses within 4 weeks before enrolment.
- Patient had major surgery within 4 weeks before enrolment.
- Patient has other serious medical condition that could potentially interfere with the
completion of treatment according to this protocol or that would impair tolerance to
therapy or prolong hematological recovery.
- Sero-positive for HIV antibody.
- Patient known to be hepatitis B surface antigen positive or who has an active
hepatitis C infection.
- Patient has an active systemic infection requiring treatment.
- Female patient is pregnant or breast feeding.
- Compromised renal function as evidenced by measured or calculated creatinine
clearance <= 50 ml/min.
- Subject is currently enrolled in, or has not yet completed at least 30 days since
ending another investigational device or drug trial or is receiving other
investigational agent.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Number of CD34+ peripheral blood stem cells/kg
Outcome Time Frame:
day 8 (and 9, if necessary)
Safety Issue:
No
Principal Investigator
Thomas Pabst, Associate Professor
Investigator Role:
Principal Investigator
Investigator Affiliation:
Dep. Medical Oncology, Bern University Hospital
Authority:
Switzerland: Independent Local Research Ethic Commission (Ethikkommission)
Study ID:
236/09
NCT ID:
NCT01220375
Start Date:
April 2010
Completion Date:
December 2011
Related Keywords:
- Myeloma
- Mobilization of autologous peripheral blood progenitor cells PBPC
- Autologous stem cell mobilization
- Multiple Myeloma
- Plerixafor
- Multiple Myeloma
- Neoplasms, Plasma Cell
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