An Evaluation of Safety and Efficacy of Escalating Doses of AMD3100 to Mobilize CD34+ Cells in Healthy Volunteers

NCT00322127 | Completed Phase 1 FDA Drug

• 2 other identifiers: 06015606-H-0156
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

This study will determine how safely and well people can tolerate AMD3100 at larger than normal doses to mobilize CD34+ cells, (stem cells). AMD3100 is a new drug designed to mobilize stem cells for transplantation in cancer patients. It pushes those cells into the circulation, making it easier to collect them, and it temporarily increases the number of stem cells in a person's blood. Patients ages 18 to 50 in good health and who are not pregnant or breastfeeding may be eligible for this study. They will undergo the following tests and procedures:

• History and physical examination
• Review of medications, including those prescribed and over-the-counter, as well as nutritional supplements
• Blood tests for liver, kidneys, and other functions; and for infections including hepatitis and AIDS
• Pregnancy test
• Electrocardiogram On the day they receive AMD3100, patients will be admitted to the Clinical Center. They will receive two doses, injected under the skin, at intervals separated by 14 to 90 days. Dose levels are 240 and 320 micrograms/kg and 400 and 480 micrograms/kg. For 24 hours following the first AMD3100 administration, blood will be collected periodically through a plastic tube at amounts dependent on doses of AMD3100 given. If patients receive one of the two highest doses, their heart rhythm will be monitored continuously during the hospital stay. From 7 to 10 days following administration of AMD3100, patients will give blood samples to monitor the effects. The second dose of AMD3100 will be given 14 to 90 days after the first one. Patients will return to the Clinical Center for the same procedures as done previously, but the dose of the drug will be higher. Risks involve side effects of AMD3100. In previous studies, patients who received the drug experienced a temporary increase in white blood cell counts. Serious side effects have included abnormally low platelet clot, abnormal heart rhythm, and low blood pressure. Patients will be carefully monitored for such effects.

Conditions

Healthy Volunteers

Keywords

Hematopoietic Stem Cells; Mobilization; CXCR4; SDF-1; Mozobil; Healthy Volunteer; HV

Outcome Measures

Primary Outcomes (1)

• To assess the safety and tolerability profile of AMD3100 when administered in escalating higher doses in humans.

  safety and tolerability

  all

Study Arms (4)

1

EXPERIMENTAL

AMD3100 given as a single 240 g/kg dose followed 14-90 days later by a single 320 g/kg dose

Drug: AMD3100

2

EXPERIMENTAL

AMD3100 given as a single 320 g/kg dose followed 14-90 days later by a single 400 g/kg dose

Drug: AMD3100

3

EXPERIMENTAL

AMD3100 given as a single 400 g/kg dose followed 14-90 days later by a single 480 g/kg dose.

Drug: AMD3100

4

EXPERIMENTAL

randomized to either receive 240 g/kg first followed by 480 g/kg after a washout period or 480 g/kg first followed by 240 g/kg after a washout period.

Drug: AMD3100

Interventions

AMD3100 DRUG

a 2 mL clear glass vial containing 1.7 mL of a sterile isotonic solution.

1; 2; 3; 4

Eligibility Criteria

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

You may qualify if:

• Ages greater than or equal to18 years and less than or equal to 50 years
• Normal renal function: creatinine less than 1.5 mg/dl
• Normal liver function: total bilirubin less than 1.5mg/dl, ALT and AST levels must be below the laboratory's high normal value.
• Normal blood count:
• WBC 3000-10000/mm(3)
• Granulocytes greater than 1500/mm(3)
• Platelets greater than 150,000/mm(3), and
• Hemoglobin (females greater than 11.1 g/dl, males greater than 12.7 g/dl)
• Antecubital veins must be adequate for peripheral access for phlebotomy (subject must be eligible for normal blood donation)
• Ability to comprehend the investigational nature of the study and provide informed consent

You may not qualify if:

• Active infection or history of recurrent infection, hepatitis B and C (HBsAg, Anti-HCV), HIV and/or HTLV-1
• History of autoimmune disease such as rheumatoid arthritis, systemic lupus erythematous
• History of cancer within the past 5 years excluding basal cell or squamous cell carcinoma of the skin
• History of any hematologic disorders including thromboembolic disease
• History of cardiac disease such as uncontrolled hypertension, peripheral vascular disease, myocardial infarction, cardiac arrhythmias or related symptoms such as tachycardia, chest pain, shortness of breath which have required medical intervention or treatment or a Framingham coronary disease risk prediction score of greater than 10% 10 year CHD risk
• History of cerebrovascular disease, transient ischemic attack, or stroke
• Pregnant or lactating

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Gyger M, Stuart RK, Perreault C. Immunobiology of allogeneic peripheral blood mononuclear cells mobilized with granulocyte-colony stimulating factor. Bone Marrow Transplant. 2000 Jul;26(1):1-16. doi: 10.1038/sj.bmt.1702464.

  PMID: 10918400 BACKGROUND

• Srour EF, Leemhuis T, Brandt JE, vanBesien K, Hoffman R. Simultaneous use of rhodamine 123, phycoerythrin, Texas red, and allophycocyanin for the isolation of human hematopoietic progenitor cells. Cytometry. 1991;12(2):179-83. doi: 10.1002/cyto.990120213.

  PMID: 2049974 BACKGROUND

• Bender JG, Unverzagt KL, Walker DE, Lee W, Van Epps DE, Smith DH, Stewart CC, To LB. Identification and comparison of CD34-positive cells and their subpopulations from normal peripheral blood and bone marrow using multicolor flow cytometry. Blood. 1991 Jun 15;77(12):2591-6.

  PMID: 1710512 BACKGROUND

• Pantin J, Purev E, Tian X, Cook L, Donohue-Jerussi T, Cho E, Reger R, Hsieh M, Khuu H, Calandra G, Geller NL, Childs RW. Effect of high-dose plerixafor on CD34+ cell mobilization in healthy stem cell donors: results of a randomized crossover trial. Haematologica. 2017 Mar;102(3):600-609. doi: 10.3324/haematol.2016.147132. Epub 2016 Oct 20.

  PMID: 27846612 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Interventions

plerixafor

Study Officials

• Richard W Childs, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2006
• First Posted: May 5, 2006
• Study Start: June 14, 2006
• Primary Completion: January 23, 2015
• Study Completion: January 23, 2015
• Last Updated: October 8, 2020

Record last verified: 2020-10

Locations

US (1)