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

NCT01206075 | Completed DMC

• 3 other identifiers: 36078-BP01HL0537502P01HL053750
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Beta-Thalassemia

Keywords

Beta Thalassemia Major; Hematopoietic Stem Cell Mobilization; Gene Transfer Techniques

Outcome Measures

Primary Outcomes (1)

• Safety and effectiveness of Mozobil for mobilization of patients with beta thalassemia major

  i) To determine the safety of peripheral blood stem cell (PBSC) mobilization with Mozobil alone or with Mozobil + G-CSF in adults with b-thalassemia major ii) To collect with Mozobil or Mozobil+G-CSF a total of at least 6 X 10e6 CD34+ cells/kg for a subsequent clinical beta-globin gene transfer trial.

  Five weeks

Secondary Outcomes (1)

• Clonogenic capacity, transducibility, and engraftment potential (in a mouse model) of genetically modified cells

  Six months

Study Arms (3)

Mozobil + G-CSF - 001

OTHER

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

Drug: Mozobil

Mozobil

OTHER

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

Drug: Mozobil

Mozobil + G-CSF - 002

OTHER

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.

Drug: Mozobil

Interventions

Mozobil 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.

Also known as: Plerixafor, AMD 3100

Mozobil + G-CSF - 002

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Washington: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• George Papanicolaou Hospital: collaborator
• Genzyme, a Sanofi Company: collaborator

Study Sites (1)

George Papanicolaou Hospital

Thessaloniki, Greece

Location

MeSH Terms

Conditions

beta-Thalassemia

Interventions

plerixafor

Condition Hierarchy (Ancestors)

Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Thalia Papayannopoulou, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Medicine, Hematology

Study Record Dates

• First Submitted: September 20, 2010
• First Posted: September 21, 2010
• Study Start: October 1, 2010
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2014
• Last Updated: December 30, 2014

Record last verified: 2014-12

Locations

GR (1)