Healthy VolunteersPhase 1NCT00322127
An Evaluation of Safety and Efficacy of Escalating Doses of AMD3100 to Mobilize CD34+ Cells in Healthy Volunteers
A Phase 1 study testing AMD3100 in people with Healthy Volunteers, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- AMD3100
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Jun 2006to 23 Jan 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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)
Show all 10Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: A Pilot Study of the Safety and Activity of Escalating Doses of AMD3100 to Mobilize CD34+ Cells in Healthy Volunteers
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:
Read more
- 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.
Read the detailed description
Peripheral blood progenitor cells (PBPC) have become the preferred source of hematopoietic stem cells for allogeneic transplantation because of technical ease of collection and shorter time required for engraftment. Traditionally, granulocyte-colony stimulating factor (G-CSF) has been used to procure the PBPC graft. Although regimens using G-CSF usually succeed in collecting adequate numbers of PBPC from healthy donors, 5%-10% of subjects will mobilize progenitor cells poorly and may require multiple large volume apheresis or bone marrow harvesting.
AMD3100 is a bicyclam compound that inhibits the binding of stromal cell derived factor-1 (SDF-1) to its cognate receptor CXCR4. CXCR4 is present on CD34+ hematopoietic progenitor cells and its interaction with SDF-1 plays a pivotal role in the homing of CD34+ cells in the bone marrow. Inhibition of the CXCR4-SDF-1 axis by AMD3100 releases CD34+ cells into the circulation, which can then be collected easily by apheresis. Recently, several reports have demonstrated that large numbers of progenitor CD34+ cells are rapidly mobilized in healthy volunteers following a single subcutaneous injection of AMD3100. The ability to collect a large quantity of PBPC's with a single injection of this drug makes this an attractive agent for mobilizing both autologous and allogeneic donors for hematopoietic stem cell transplantation.
A phase one dose escalating trial of AMD3100 in healthy donors done outside the NHLBI suggested the peak CD34+ mobilizing effects of this agent occurred at the 240 microgram/kg dose. Of note, no dose limiting toxicities were observed at the highest dose level of 320 mcg/kg. In two current trials at the NHLBI, AMD3100 has also proven to be well tolerated at the 240 mcg/kg dose, however, the progenitor CD34+ cell yield following a matched volume apheresis was lower compared to G-CSF mobilizations collected from the same healthy volunteers. More importantly, the number of CD34+ cells collected following one dose of AMD3100 has frequently been less than 3 x 10(6) CD34+ cells/kg, the previously defined minimal dose of progenitor cells required to optimize allogeneic hematopoietic stem cell transplantation outcomes. In addition, preliminary data from non-human primate studies suggest that higher doses of AMD3100 may improve CD34+ cell yield in an apheresis collection.
Based on these data, it is possible that inter-subject variability in CD34+ cell mobilization may have led investigators (in the prior phase I study) to prematurely terminate AMD3100 dose escalation based on the perception that CD34+ doses had peaked. We therefore propose this dose escalating study, designed to evaluate the safety and activity of AMD3100 when administered in escalating higher doses (240 microgram/kg dose, 320 microgram/kg dose 400 microgram/kg dose 480 microgram/kg dose). Activity will be evaluated by measuring the most effective dose of AMD3100 in mobilizing progenitor CD34 + cells into the circulation in healthy donors. To minimize inter-subject variability, we will administer two different doses of AMD3100 to each subject, evaluating the peak CD34+ cell count achieved after each dose. Separate cohorts of healthy volunteers will be evaluated for each dose escalation. The short half life and rapid wash-out of AMD3100 allows for this method of study.
- Conditions
- Healthy Volunteers
- Being tested
- AMD3100
- Keywords
- Hematopoietic Stem Cells, Mobilization, CXCR4, SDF-1, Mozobil, Healthy Volunteer, HV
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMD3100Drug
a 2 mL clear glass vial containing 1.7 mL of a sterile isotonic solution.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | AMD3100 given as a single 240 g/kg dose followed 14-90 days later by a single 320 g/kg dose Receives: 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 Receives: 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. Receives: 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. Receives: Drug: AMD3100 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the safety and tolerability profile of AMD3100 when administered in escalating higher doses in humans.
safety and tolerability
Measured: all
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2006 (estimated)
- Study start14 Jun 2006
- Primary completion23 Jan 2015
- Study completion23 Jan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Richard W Childs, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00322127
- Sponsor's protocol ID
- 060156
- Other IDs
- 06-H-0156
- Status last verified
- Oct 2020
- First submitted
- 4 May 2006
- Last updated
- 8 Oct 2020
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 10918400Srour 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.
PubMed 2049974Bender 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.
PubMed 1710512Pantin 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.
PubMed 27846612
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of the Safety and Activity of Escalating Doses of AMD3100 to Mobilize CD34+ Cells in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT00322127
- Acronym / sponsor ID
- 060156
- Conditions
- Healthy Volunteers
- Keywords
- Hematopoietic Stem Cells, Mobilization, CXCR4, SDF-1, Mozobil, Healthy Volunteer, HV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 14 Jun 2006 (actual)
- Primary completion
- 23 Jan 2015 (actual)
- Study completion
- 23 Jan 2015 (actual)
- First posted
- 5 May 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Peripheral blood progenitor cells (PBPC) have become the preferred source of hematopoietic stem cells for allogeneic transplantation because of technical ease of collection and shorter time required for engraftment. Traditionally, granulocyte-colony stimulating factor (G-CSF) has been used to procure the PBPC graft. Although regimens using G-CSF usually succeed in collecting adequate numbers of PBPC from healthy donors, 5%-10% of subjects will mobilize progenitor cells poorly and may require multiple large volume apheresis or bone marrow harvesting.
AMD3100 is a bicyclam compound that inhibits the binding of stromal cell derived factor-1 (SDF-1) to its cognate receptor CXCR4. CXCR4 is present on CD34+ hematopoietic progenitor cells and its interaction with SDF-1 plays a pivotal role in the homing of CD34+ cells in the bone marrow. Inhibition of the CXCR4-SDF-1 axis by AMD3100 releases CD34+ cells into the circulation, which can then be collected easily by apheresis. Recently, several reports have demonstrated that large numbers of progenitor CD34+ cells are rapidly mobilized in healthy volunteers following a single subcutaneous injection of AMD3100. The ability to collect a large quantity of PBPC's with a single injection of this drug makes this an attractive agent for mobilizing both autologous and allogeneic donors for hematopoietic stem cell transplantation.
A phase one dose escalating trial of AMD3100 in healthy donors done outside the NHLBI suggested the peak CD34+ mobilizing effects of this agent occurred at the 240 microgram/kg dose. Of note, no dose limiting toxicities were observed at the highest dose level of 320 mcg/kg. In two current trials at the NHLBI, AMD3100 has also proven to be well tolerated at the 240 mcg/kg dose, however, the progenitor CD34+ cell yield following a matched volume apheresis was lower compared to G-CSF mobilizations collected from the same healthy volunteers. More importantly, the number of CD34+ cells collected following one dose of AMD3100 has frequently been less than 3 x 10(6) CD34+ cells/kg, the previously defined minimal dose of progenitor cells required to optimize allogeneic hematopoietic stem cell transplantation outcomes. In addition, preliminary data from non-human primate studies suggest that higher doses of AMD3100 may improve CD34+ cell yield in an apheresis collection.
Based on these data, it is possible that inter-subject variability in CD34+ cell mobilization may have led investigators (in the prior phase I study) to prematurely terminate AMD3100 dose escalation based on the perception that CD34+ doses had peaked. We therefore propose this dose escalating study, designed to evaluate the safety and activity of AMD3100 when administered in escalating higher doses (240 microgram/kg dose, 320 microgram/kg dose 400 microgram/kg dose 480 microgram/kg dose). Activity will be evaluated by measuring the most effective dose of AMD3100 in mobilizing progenitor CD34 + cells into the circulation in healthy donors. To minimize inter-subject variability, we will administer two different doses of AMD3100 to each subject, evaluating the peak CD34+ cell count achieved after each dose. Separate cohorts of healthy volunteers will be evaluated for each dose escalation. The short half life and rapid wash-out of AMD3100 allows for this method of study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: AMD3100AMD3100 given as a single 240 g/kg dose followed 14-90 days later by a single 320 g/kg dose |
| 2 | Experimental | Drug: AMD3100AMD3100 given as a single 320 g/kg dose followed 14-90 days later by a single 400 g/kg dose |
| 3 | Experimental | Drug: AMD3100AMD3100 given as a single 400 g/kg dose followed 14-90 days later by a single 480 g/kg dose. |
| 4 | Experimental | Drug: AMD3100randomized 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. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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.
- WBC 3000-10000/mm(3)
- Granulocytes greater than 1500/mm(3)
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AMD3100a 2 mL clear glass vial containing 1.7 mL of a sterile isotonic solution. | Drug | 1, 2, 3, 4 |
Primary outcome
To assess the safety and tolerability profile of AMD3100 when administered in escalating higher doses in humans.
Time frame: all
safety and tolerability
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2020.
- Background: PubMed 10918400Gyger 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.
- Background: PubMed 2049974Srour 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.
- Background: PubMed 1710512Bender 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.
- Derived from this study: PubMed 27846612Pantin 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard W Childs, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AMD3100 in people with Healthy Volunteers, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess the safety and tolerability profile of AMD3100 when administered in escalating higher doses in humans. (time frame: all). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00322127, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2020.