Evaluating the Safety and Effectiveness of Mozobil Mobilization in Adults With Beta-Thalassemia Major

NCT ID: NCT01206075

Last Updated: 2014-12-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-10-31

Study Completion Date

2014-12-31

Brief Summary

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Thalassemia is considered the most common genetic disorder worldwide, occurring with high frequency in Mediterranean areas, the Middle East, Southeast Asia, and the Pacific Islands. Currently, the only cure for thalassemia is bone marrow transplantation from a related, compatible donor. Gene transfer, achieved by transplantation of the patient's own blood stem cells that have been genetically-modified with the corrected gene, could potentially cure thalassemia.

The first step in developing gene transfer for treatment of thalassemia is to develop a safe and effective method to obtain blood stem cells from thalassemia patients. Eventually, high numbers of genetically modified cells will need to be infused into the patient for clinical gene transfer to be effective. The blood stem cells are obtained by giving a "mobilization" agent to the patients. This causes the stem cells to leave the bone marrow and go into the blood. The purpose of this study is to test the safety and effectiveness of the new mobilization agent, Mozobil, in causing mobilization of blood stem cells for patients with beta-thalassemia major.

Detailed Description

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The purpose of this study is to optimize blood stem cell mobilization in adults with beta thalassemia major. We seek a method of mobilization that will be safe, with minimum side effects, and that will yield high numbers of blood stem cells. For successful gene therapy of thalassemia, high numbers of genetically modified stem cells will need to be introduced into the patient. Participants will include beta-thalassemia patients who failed to mobilize sufficiently with G-CSF (in our previous protocol) and new patients. In this study we will focus on the safety and effectiveness of mobilization with Mozobil or with Mozobil plus G-CSF. Following mobilization, blood stem cells will be recovered using leukapheresis, a procedure similar to a blood donation, in which mobilized white blood cells are collected from the blood of the patient.

During drug administration and leukapheresis, patients will be hospitalized at George Papanicolaou Hospital in Thessaloniki, Greece. Patients who failed to mobilize in the previous protocol will receive Mozobil and G-CSF and will be hospitalized for 5-8 days for the duration of drug administration and leukapheresis. They will receive G-CSF for several days; Mozobil will be added on the last few days of G-CSF. New patients will receive Mozobil only and will be hospitalized for 2-3 days for drug administration and leukapheresis. Mozobil is administered at 240µg/kg, under the skin. Participants will undergo two or three leukapheresis procedures in a row if low numbers of blood stem cells were recovered in the first (and possibly second) leukapheresis. Participants will be discharged from the hospital the day following the last leukapheresis procedure. Weekly follow-up visits will occur for the next month, either at G. Papanicolaou Hospital, or at the participant's local doctor's office. The total period of study participation is approximately 5 weeks. In the event that Mozobil alone does not cause mobilization of high levels of blood cells, patients will be invited to repeat the protocol three months later, receiving Mozobil and G-CSF.

Conditions

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Beta-Thalassemia

Keywords

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Beta Thalassemia Major Hematopoietic Stem Cell Mobilization Gene Transfer Techniques

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Mozobil + G-CSF - 001

Up to four patients (splenectomized and non-splenectomized) previously mobilized with G-CSF (previous study), who failed to yield by 2 leukaphereses sufficient CD34+ cells for a future gene therapy procedure, will receive the combination of G-CSF+Mozobil

Group Type OTHER

Mozobil

Intervention Type DRUG

Previously mobilized splenectomized patients who failed to yield sufficient numbers of cells with G-CSF in the previous study will receive low doses G-CSF subcutaneously (starting at 2.5µg/kg/day and adjusted to the degree of leukocytosis), and Mozobil at 240µg/kg starting on the 4th or 5th day of G-CSF, followed by one to three leukaphereses. Previously non-splenectomized patients who failed to yield sufficient numbers of cells with G-CSF in the previous study will receive G-CSF at 10µg/kg/day subcutaneously for 4-7 days, and Mozobil at 240µg/kg starting on the 4th or 5th day of G-CSF, followed by one to three leukaphereses.

Mozobil

Sixteen or more patients (non-splenectomized and splenectomized) who were not previously mobilized will receive Mozobil alone.

Group Type OTHER

Mozobil

Intervention Type DRUG

Up to sixteen patients (splenectomized and non-splenectomized) who were not previously mobilized will receive Mozobil at 240µg/kg for one to three days, followed by one to three leukaphereses.

Mozobil + G-CSF - 002

Patients who, in this study, fail to mobilize sufficient yields of blood stem cells with Mozobil alone will be invited to be re-mobilized with the combination of Mozobil plus G-CSF.

Group Type OTHER

Mozobil

Intervention Type DRUG

Previously mobilized splenectomized patients who failed to yield sufficient numbers of cells with Mozobil alone will receive low doses G-CSF subcutaneously (starting at 2.5µg/kg/day and adjusted to the degree of leukocytosis), and Mozobil at 240µg/kg starting on the 4th or 5th day of G-CSF, followed by one to three leukaphereses. Previously non-splenectomized patients who failed to yield sufficient numbers of cells with Mozobil alone will receive G-CSF at 10µg/kg/day subcutaneously for 4-7 days, and Mozobil at 240µg/kg starting on the 4th or 5th day of G-CSF, followed by one to three leukaphereses.

Interventions

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Mozobil

Previously mobilized splenectomized patients who failed to yield sufficient numbers of cells with Mozobil alone will receive low doses G-CSF subcutaneously (starting at 2.5µg/kg/day and adjusted to the degree of leukocytosis), and Mozobil at 240µg/kg starting on the 4th or 5th day of G-CSF, followed by one to three leukaphereses. Previously non-splenectomized patients who failed to yield sufficient numbers of cells with Mozobil alone will receive G-CSF at 10µg/kg/day subcutaneously for 4-7 days, and Mozobil at 240µg/kg starting on the 4th or 5th day of G-CSF, followed by one to three leukaphereses.

Intervention Type DRUG

Mozobil

Previously mobilized splenectomized patients who failed to yield sufficient numbers of cells with G-CSF in the previous study will receive low doses G-CSF subcutaneously (starting at 2.5µg/kg/day and adjusted to the degree of leukocytosis), and Mozobil at 240µg/kg starting on the 4th or 5th day of G-CSF, followed by one to three leukaphereses. Previously non-splenectomized patients who failed to yield sufficient numbers of cells with G-CSF in the previous study will receive G-CSF at 10µg/kg/day subcutaneously for 4-7 days, and Mozobil at 240µg/kg starting on the 4th or 5th day of G-CSF, followed by one to three leukaphereses.

Intervention Type DRUG

Mozobil

Up to sixteen patients (splenectomized and non-splenectomized) who were not previously mobilized will receive Mozobil at 240µg/kg for one to three days, followed by one to three leukaphereses.

Intervention Type DRUG

Other Intervention Names

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Plerixafor AMD 3100 Plerixafor AMD3100 Plerixafor AMD3100

Eligibility Criteria

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Inclusion Criteria

* Βeta- thalassemia major
* Age \>18\<50
* Karnofsky performance status ³80%
* Splenectomized patients or patients with spleen volume \<800cm3 (only for the non splenectomized patients who will receive Mozobil + G-CSF)
* Compliant with regular transfusions and regular chelation
* Liver iron by MRI \<280μmol/gr or ³1.7msec by T2\*MRI
* Heart iron by MRI \>2.8 (SI/SD) or ³9msec by T2\*MRI
* Hepatitis B or C virus load negative by PCR (polymerase chain reaction)
* Left ventricular ejection fraction (LVEF) \>45% by echocardiogram
* Adequate respiratory function with DLCO \>50%
* Negative pregnancy test, if female
* Ability to give informed consent and willingness to meet all the expected requirements of the protocol for the duration of the study

Exclusion Criteria

* History of thrombosis or known thrombophilia
* Symptomatic viral, bacterial or fungal infection within 6 weeks prior eligibility evaluation
* Pregnancy or lactation
* HIV positivity
* History of malignancy, other than local skin cancer
* Other systematic disease non thalassemia-associated
* Splenectomized patients with platelet count \>900,000 (only for the splenectomized patients who will receive low dose G-CSF+ Mozobil)
* Additional risk factors for thrombosis, including Factor V Leiden; antiphospholipid antibodies and less than 50% of the lowest normal value for the following procoagulants: antithrombin 3, protein C, or protein S.
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

George Papanicolaou Hospital

OTHER

Sponsor Role collaborator

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role collaborator

University of Washington

OTHER

Sponsor Role lead

Responsible Party

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Thalia Papayannopoulou

Professor, Medicine, Hematology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Thalia Papayannopoulou, MD

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Locations

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George Papanicolaou Hospital

Thessaloniki, , Greece

Site Status

Countries

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Greece

Other Identifiers

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P01HL053750

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2P01HL053750

Identifier Type: NIH

Identifier Source: secondary_id

View Link

36078-B

Identifier Type: -

Identifier Source: org_study_id