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Currently Enrolling Trials

General Information

Mozobil is a hematopoietic stem cell mobilizer and inhibitor of the CXCR4 chemokine receptor. CXXR4 is specific for stromal-derived-factor-1 (SDF-1), a molecule endowed with potent chemotactic activity for lymphocytes. Because the interaction between SDF-1 and CXCR4 plays an important role in holding hematopoietic stem cells in the bone marrow, drugs that block the CXCR4 receptor appear to be capable of "mobilizing" hematopoietic stem cells into the bloodstream.

Mozobil, in combination with granulocyte-colony stimulating factor (G-CSF), is specifically indicated to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM).

Mozobil is supplied as a solution designed for subcutaneous injection. Treatment with Mozobil should begin after the patient has received G-CSF once daily for four days. Mozobil should be administered approximately 11 hours prior to initiation of apheresis for up to 4 consecutive days. The recommended initial dose of the drug is 0.24 mg/kg body weight by subcutaneous (SC) injection. The dose should not exceed 40 mg/day. In patients with moderate and severe renal impairment (estimated creatinine clearance (CLCR) = 50 mL/min), the dose of Mozobil should be reduced by one-third, to 0.16 mg/kg.

Clinical Results

FDA Approval
FDA approval of Mozobil was based on the results of two placebo-controlled clinical trials: Study 1 and Study 2. In both studies, the subjects were randomized to receive either Mozobil 0.24 mg/kg or placebo on each evening prior to apheresis. They received daily morning doses of G-CSF 10 micrograms/kg for 4 days prior to the first dose of Mozobil or placebo and on each morning prior to apheresis.

Study 1
This study enrolled 298 subjects with non-Hodgkin's lymphoma. Data showed that 59% of the subjects with NHL who were mobilized with Mozobil and G-CSF collected ≥ 5 X 106 CD34+ cells/kg from the peripheral blood in four or fewer apheresis sessions, compared with 20% of patients who were mobilized with placebo and G-CSF (p < 0.001). The median number of days to reach ≥ 5 x 106 CD34+ cells/kg was 3 days for the Mozobil group and not evaluable for the placebo group.

Study 2
This trial enrolled 302 subjects with multiple myeloma. Data showed that 72% of MM patients who were mobilized with Mozobil and G-CSF collected ≥ 6 X 106 CD34+ cells/kg from the peripheral blood in two or fewer apheresis sessions, compared with 34% of patients who were mobilized with placebo and G-CSF (p < 0.001). The median number of days to reach ≥ 6 x 106 CD34+ cells/kg was 1 day for the Mozobil group and 4 days for the placebo group.

Ongoing Study Commitments

Genzyme has agreed to provide follow up safety and efficacy information for trial 3101-LTF for 5 years which will include death and disease status (relapse or disease-free). Updated status reports to be submitted annually.
Protocol Submission Date: April 3, 2006
Trial Start Date: December 15, 2006
First Annual Report: February 2010
Second Annual Report: February 2011
Third Annual Report: February 2012
Fourth Annual Report: February 2013
Fifth Annual Report: February 2014
Genzyme has agreed to provide follow up safety and efficacy information for trial 3102-LTF for 5 years which will include death and disease status (relapse or disease-free). Updated status reports to be submitted annually.
Protocol Submission Date: April 20, 2006
Trial Start Date: January 11, 2007
First Annual Report: February 2010
Second Annual Report: February 2011
Third Annual Report: February 2012
Fourth Annual Report: February 2013
Fifth Annual Report: February 2014
Genzyme has agreed to complete and submit the data and final report from the thorough QT/QTc trial.
Protocol Submission: October 24, 2007
Trial Start: March 31, 2008
Final Report Submission: by January 31, 2009

Side Effects

Adverse events associated with the use of Mozobil may include, but are not limited to, the following:

Diarrhea
Nausea
Fatigue
Injection site reactions
Headache
Arthralgia
Dizziness
Vomiting

Mechanism of Action

Mozobil is a hematopoietic stem cell mobilizer and inhibitor of the CXCR4 chemokine receptor. It blocks the binding of the CXCR4 cognate ligand, stromal cell-derived factor-1a (SDF-1a). SDF-1a and CXCR4 are recognized to play a role in the trafficking and homing of human hematopoietic stem cells to the marrow compartment. Once in the marrow, stem cell CXCR4 can act to help anchor these cells to the marrow matrix, either directly via SDF-1a or through the induction of other adhesion molecules.

Literature References

Stewart DA, Smith C, MacFarland R, Calandra G Pharmacokinetics and pharmacodynamics of plerixafor in patients with non-Hodgkin lymphoma and multiple myeloma. Biology of Blood and Bone Marrow Transplant 2009 Jan;15(1):39-46

Jin P, Wang E, Ren J, Childs R, Shin JW, Khuu H, Marincola FM, Stroncek DF Differentiation of two types of mobilized peripheral blood stem cells by microRNA and cDNA expression analysis. Journal of Translational Medicine 2008 Jul 22;6:39

Cashen A, Lopez S, Gao F, Calandra G, MacFarland R, Badel K, DiPersio J A phase II study of plerixafor (AMD3100) plus G-CSF for autologous hematopoietic progenitor cell mobilization in patients with Hodgkin lymphoma. Biology of Blood and Marrow Transplantation 2008 Nov;14(11):1253-61