Neoplasms

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Neoplasms by Histologic Type

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Immunoproliferative Disorders

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Anti-Infective Agents

All Drugs and Chemicals

Plerixafor

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

They will receive Plerixafor (240 µg/kg/day subcutaneously for 1 dose) on Day 0 at 8 am

Plerixafor (Mozobil)

They will receive G-CSF (5 µg/kg/day) for 4 days (Days -4,-3,-2,-1 at 8 am) followed by Plerixafor (240 µg/kg/day subcutaneously for 1 dose) on Day 0 at 8 am

Plerixafor + G-CSF

Stephen Couban

Stem cells can be transplanted from a healthy donor to a patient to combat blood cancers and other disorders. This process is called stem cell transplantation. Stem cells normally live in the bone marrow. A bone marrow transplantation (BMT) is when the bone marrow is directly transplanted into a patient. However, stem cells can also be stimulated to move from the bone marrow to the blood where they can be collected, a process is called mobilization. When these stem cells are transplanted it is called peripheral blood stem cell transplantation (PBSCT). Both stem cell sources are used for different reasons, but PBSCT is much more common.

There is considerable debate as to which stem cell source, BMT or PBSCT, is optimal. There are differences between the two sources in important transplant outcomes. The stem cell product that is transplanted, also called the stem cell graft, contains more than just stem cells. Results from studies suggest that the variation in the cells with grafts may account for the variation in outcomes. Preliminary data from a recent study conducted by the Canadian Blood and Bone Marrow Transplant Group has associated relative frequencies of particular cell populations with leukemic relapse and another important outcome called graft versus host disease (GVHD). While the later essentially equates to a failed transplant, the former is the most common and devastating complication of stem cell transplantation.

The only drug used to mobilize stem cells into the blood of health donors for collection is G-CSF. However there is a new mobilization drug recently approved called plerixafor. This drug is able to mobilize stem cells when G-CSF has failed and pre-clinical studies suggest that it may produce a superior stem cell graft to G-CSF alone. There is little information available, besides safety and efficacy data, about the effects that plerixafor has on the stem cell graft of normal healthy donors.

This study will compare the stem cell graft in normal healthy donors following plerixafor mobilization versus plerixafor and G-CSF mobilization. Specifically, they will look at the cell populations that have been previously correlated with important transplantation outcomes like relapse and GVHD. The investigators suspect that the stem cell graft mobilized by plerixafor and G-CSF will provide a superior graft to that mobilized by plerixafor alone.

Background:

Stem cell transplantation (SCT) involves transfusing stem cells collected from 3 potential sources: bone marrow, peripheral blood, or umbilical cord. There are 2 major types of transplantation. Autologous SCT involves transplanting the patients own stem cells, while allogeneic transplantation involves transplanting stem cells from someone else. Whatever the source, the transplanted stem cell product is called the graft. Currently, the most common source is peripheral blood, However, there is considerably debate as to the optimal stem cell source because different sources have been associated with different transplant outcomes. One key outcome is graft versus host disease (GVHD). This is the most common complication of SCT and contributes significantly to transplant morbidity and mortality, as well as relapse.

Stem cells normally populate the bone marrow. Drugs are used to encourage stem cells to go into the peripheral blood, a process call mobilization. In the peripheral blood stem cells can be collected and subsequently transplanted. In Canada, the only drug used to mobilize stem cells from donors is filgrastim, a form of granulocyte colony stimulating factor (G-CSF). Although well tolerated, there are some shortcomings to this agent and there is clearly room to improve in terms of the donor experience and providing the optimal stem cell graft.

A soon to be completed study conducted by the Canadian Blood and Bone Marrow Transplant Group (CBMTG), called CBMTG 0601, is evaluating the best stem cell source. The study is aimed to compare the outcomes between allogeneic transplant patients who receive either G-CSF stimulated bone marrow or peripheral blood. This will be a seminal study that should provide valuable information as to the optimal stem cell source in allogeneic SCT. Early results suggest that the investigators may be able to predict important SCT outcomes, such as transplant related mortality, relapse or graft versus host disease, by looking at cell populations in the graft.

Plerixafor is a new mobilization agent that is approved for use in combination with neupogen in myeloma and relapsed lymphoma who are undergoing an autologous SCT. Following numerous publications on the safety and dosing of plerixafor, there were 2 pivotal high quality studies performed in this patient population. The results of this study lead to FDA approval, and Health Canada approval is close. Plerixafor may be a clinically superior mobilizing agent to Neupogen. More importantly though, it has a formidable safety profile and arguably superior in this respect. There has also been a case report and a trial demonstrating both the safety and efficacy of plerixafor in healthy donors as well. Finally, preclinical work suggests that plerixafor mobilization may yield a superior graft. Taken together, this work supports the notion that plerixafor may be a superior mobilization agent over neupogen.

Rationale:

Considering the shortcomings of neupogen and the demonstrated potential of plerixafor in trials with autologous SCT patients, it would be logical to further investigate the efficacy of plerixafor in normal healthy donors for allogeneic SCT. The investigators can confidently state that plerixafor is safe. Furthermore, plerixafor can mobilize myeloma and lymphoma patients who have failed neupogen mobilization. However, although suggested in preclinical data, there is no firm evidence to suggest that plerixafor mobilization provides a superior stem cell graft. The investigators will administer either plerixafor or plerixafor and neupogen then compare the cell populations in both peripheral blood and bone marrow..

Importance:

The use of SCT has steadily increased in the last 20 years. This has especially increased since using neupogen to mobilize stem cells thereby making transplants easier. Now that there is a new agent available that is likely safer and perhaps more efficacious, its use may improve both donor experience and patient outcomes. If plerixafor grafts consist of cell populations that are associated with superior transplant outcomes as determined in CBMTG 0601, then it will likely be used in an upcoming larger clinical trial comparing neupogen and plerixafor in normal healthy donors.

Objectives:

Our primary objective is to determine the best timing for harvesting stem cells from normal donors given plerixafor with or without neupogen. A secondary objective is to evaluate and compare the change over time after plerixafor with or without neupogen administration on the population of cells in the graft predicted to give superior transplant outcomes. The other secondary objective is to evaluate and compare the change over time after plerixafor with or without neupogen administration on the concentration of cells in the PB and BM of normal donors predicted to give GVHD or relapse. The investigators hypothesise that plerixafor with neupogen will provide a graft with increased cell populations associated with superior SCT outcomes.

Healthy Donor Study II - Comparing Plerixafor With G-CSF and Plerixafor

A Pilot Study To Design a Clinical Trial That Will Compare the Ability of Plerixafor Alone Versus Plerixafor Plus G-CSF To Generate a Bone Marrow Versus Blood Transplant Product In Normal Healthy Adults

The frequency of CD34+ and CD34+CD38- cells in a graft has been show to be an excellent measure of hematopoietic engrafting potential.

Relative frequencies of CD56bright NK cells, CD4+ central memory T-cells, perforin+ CD8+ T-cells, and CD19+ CD27-TLR9+ B-cells has been associated with GVHD.

A high frequency of CD56bright NK cells in the stem cell graft has been associated with low leukemia relapse.

Genzyme, a Sanofi Company

Hematologist

Heart and Blood Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Antineoplastic Agents

Lenograstim

Bortezomib

Bortezomib injection:

1.3mg/m2 11 days before and 8 days before the stem cell collection

G-CSF injection:

10mcg/kg on days -4 to day -1 once daily

bortezomib and G-CSF

Sunil Abhyankar, MD

The purpose of this study is to determine if the combination of G-CSF and bortezomib is safe and effective in blood cell mobilization.

The study plans to use VELCADE for two doses followed by G-CSF given for 4 doses as is standard for mobilization with G-CSF alone. The rationale for VELCADE prior to the G-CSF is because VELCADE causes thrombocytopenia, similar to how cyclophosphamide is given followed by G-CSF for stem cell mobilization. Usually a cycle of VELCADE for myeloma therapy consists of 4 doses, but this may result in more significant drop in the platelet count. Low platelet counts may preclude adequate stem cell collection. The mobilization with VELCADE and GCSF will be approximately 3 -4 weeks after completion of the initial therapy for the primary disease.

Patients meeting eligibility criteria and who give informed consent will be mobilized using bortezomib at 1.3mg/m2 on day -11 and day -8. Subsequently G-CSF will be administered subcutaneously from day -4 to day -1 as a once daily injection at the standard /established dose of 10mcg/kg. Stem cell collection will be done on day 0 per standard of care regimen and protocol with processing of 4 -5 blood volumes. Stem cell enumeration by flow cytometry will be done prior to the collection by flow cytometry. The number of CD 34 positive cells (stem cell phenotype) / kg obtained each day of collection will be noted. G-CSF will be continued daily until adequate numbers of stem cells are obtained for the performance of a single autologous transplant (\> 2.5 million CD 34 cells/kg of weight. Subsequently the data for engraftment of neutrophils and platelets will be monitored as is routine for all patients undergoing autologous transplant.

A Safety Study Looking at the Combination of Velcade and G-CSF in Patients With Myeloma or Lymphoma

A Pilot Trial to Assess Mobilization of Hematopoietic Progenitor Cells With a Combination of Bortezomib and G-CSF in Patients Undergoing Autologous Transplant for Myeloma and Lymphoma

The primary aim of this single-arm pilot study is to determine the effectiveness of a combination of Bortezomib and G-SCSF in blood stem cell mobilization through the estimation of the proportion of patients receiving treatment that obtain adequate stem cell yield.

Assess the safety of the study mobilization regimen

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Healthy Donor Study II - Comparing Plerixafor With G-CSF and Plerixafor	NCT01403896	Malignant Lymph...	Plerixafor (Moz... Plerixafor + G-...	18 Years - 30 Years	Nova Scotia Health Authority
Healthy Donor Study II - Comparing Plerixafor With G-CSF and Plerixafor	NCT01403896	Malignant Lymph...	Plerixafor (Moz... Plerixafor + G-...	18 Years - 30 Years	Nova Scotia Health Authority
A Safety Study Looking at the Combination of Velcade and G-CSF in Patients With Myeloma or Lymphoma	NCT01171092	Malignant Lymph... Autologous Tran...	bortezomib and ...	18 Years -	University of Kansas Medical Center
A Safety Study Looking at the Combination of Velcade and G-CSF in Patients With Myeloma or Lymphoma	NCT01171092	Malignant Lymph... Autologous Tran...	bortezomib and ...	18 Years -	University of Kansas Medical Center

Spots Global Cancer Trial Database for malignant lymphoma, stem cell type