ATRA Plus G-CSF for Mobilization of Hematopoietic Stem and Progenitor Cells
Summary
Hematopoietic stem and progenitor cells (HSPC) are used for transplantation in patients undergoing high dose therapy for the treatment of a range of cancers.
- HSPC are collected from the bloodstream after treatment with medications that cause the HSPC to move from the bone marrow into the bloodstream, a process called mobilization
- between 5 and 60% of patients can fail to collect enough HSPC for a transplant, using current mobilization techniques
- this study aims to assess the safety of combining a derivative of vitamin A, ATRA with G-CSF (the drug most commonly used to mobilize HSPC)
- ATRA has never been combined with G-CSF for mobilization of HSPC and therefore a study is needed to assess the safety of this combination, and whether it successfully mobilizes HSPC
Description
HSPC mobilization is normally achieved using cytokines such as G-CSF, or occasionally GM-CSF, often in combination with myelosuppressive chemotherapy.
Studies in the mouse model have shown that retinoids (vitamin A derivatives) can be combined with G-CSF, and that this combination synergizes to enhance HSPC mobilization over that seen with G-CSF alone.
This trial aims to assess the safety and mobilization efficacy of combining mobilizing doses of G-CSF with a standard dose of ATRA, using a treatment regimen derived from the earlier murine studies.
In this phase I pilot study, six patients with multiple myeloma or cutaneous lymphoma will be treated with ATRA plus G-CSF, and safety and toxicity data collected for the two week study drug period plus a further two weeks' follow-up. The primary endpoint is safety and toxicity, the secondary endpoint is an observation of the mobilization efficacy as demonstrated by CD34+ cell counts over the study period. Patients will not undergo stem cell collection during this study, as this is purely an observational study. Participating patients will not be those who would normally be scheduled for stem cell collection and transplantation in the near future, but rather patients with stable disease who are not candidates for imminent transplantation, or who have collected adequate HSPC on previous mobilization attempts and are currently being observed.
Cutaneous lymphoma and multiple myeloma are chosen as suitable disease states for this study as there is in vitro evidence of a possible disease benefit of retinoids in these disorders. If disease response is noted during the study or follow up period, ongoing ATRA will be offered at the discretion of the treating physician.
Study Design
Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Multiple Myeloma
Intervention
ATRA plus G-CSF (filgrastim, NEUPOGEN (R)) combination
Location
Peter MacCallum Cancer Center
East Melbourne
Victoria
Australia
3002
Status
Completed
Source
Peter MacCallum Cancer Centre, Australia
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00400556
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Leukemia, Plasma Cell
A rare, aggressive variant of MULTIPLE MYELOMA characterized by the circulation of excessive PLASMA CELLS in the peripheral blood. It can be a primary manifestation of multiple myeloma or develop as a terminal complication during the disease.
Myeloma Proteins
Abnormal immunoglobulins characteristic of MULTIPLE MYELOMA.
Bence Jones Protein
An abnormal protein with unusual thermosolubility characteristics that is found in the urine of patients with MULTIPLE MYELOMA.
Hla-c Antigens
Class I human histocompatibility (HLA) antigens encoded by a small cluster of structural genes at the C locus on chromosome 6. They have significantly lower immunogenicity than the HLA-A and -B determinants and are therefore of minor importance in donor/recipient crossmatching. Their primary role is their high-risk association with certain disease manifestations (e.g., spondylarthritis, psoriasis, multiple myeloma).
Multiple Myeloma
A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY.
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