HemoglobinopathiesPhase 2NCT00153985

Allogeneic Stem Cell Transplantation Following Chemotherapy in Patients With Hemoglobinopathies

A Phase 2 study testing Busulfex, Fludarabine and Alemtuzumab in people with Hemoglobinopathies and Sickle Cell Disease, run by Dana-Farber Cancer Institute at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The purpose of this study is to determine if treatment with reduced-dose busulfex, fludarabine and alemtuzumab (CAMPATH) followed by sten cell infusion will allow for donor stem cells to grow in patients with hemoglobinopathies bone marrow and restore circulating blood counts. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Hemoglobinopathies, Sickle Cell Disease, Thalassemia
What is being tested?: Busulfex, Fludarabine and Alemtuzumab
Type of treatment: Injection or infusion, Surgery or procedure
How many people: 2 participants
Where: 6 sitesUnited States
Study dates: Mar 2004to Jul 2009
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients with sickle cell disease should have one or more of the following: acute chest syndrome requiring hospitalization; nonhemorrhagic stroke or central nervous system event lasting longer than 24 hours; recurrent caso-occlusive pain or recurrent priapism; sickle neuropathy; bilateral proliferative retinopathy and major visual impairment of at least one eye; osteonecrosis of multiple joints; transfusion dependence; vaso-occlusive.
Patients with thalassemia should have one or more of the following: transfusion dependence; iron overload; presence of 2 or more alloantibodies against red cell antigens.

Who cannot join

Pregnancy
Acute hepatitis
Cardiac ejection fraction < 30%
Severe renal impairment
Severe residual functional neurologic impairment
Evidence of HIV infection

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

United States6 sites

Winship Cancer Institute-Emory University
Atlanta, Georgia, 30322
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Massachusetts General Hospital
Boston, Massachusetts, 02115
Ohio State University College of Medicine
Columbus, Ohio, 43210
Feist-Weiller Cancer Center-LSU
Shreveport, Louisiana, 71130

Other trials in United States

About this study

Official title: Multi-Center Study Using Allogeneic Stem Cell Transplantation Following Reduced Intensity Chemotherapy in Patients With Hemoglobinopathies

Read the detailed description

In order to undergo transplant procedure, patients will be admitted to the hospital for approximately 10-14 days.
To prepare patient's bone marrow to accept donor stem cells, they will receive fludarabine and busulfex. Fludarabine will be given intravenously once daily for 4 days. Busulfex will be given once daily for the same 4 days.
One day before patients receive busulfex and fludarabine, they will also be given alemtuzumab intravenously once daily for 5 days.
Three days after the end of chemotherapy, patients will receive the infusion of donor stem cells.
If patients have thalassemia, they will receive subcutaneous injections of filgrastim starting on day one after the donor stem cell transfusion and will continue receiving filgrastim every day until it appears that the donor stem cells have been accepted. If the patient has sickle cell disease, filgrastim will not be given,
Additional drugs will be given to help prevent infection (i.e. antibiotics).
After stem cell infusion patients will be examined and have blood tests weekly for 1 month. Bone marrow biopsies, and blood work will also be performed 1 month, 3 months, 6 months and 1 year after stem cell infusion.
Patients will be on the study for about 12 months. After study is completed progress will be monitored on an annual basis.

Conditions: Hemoglobinopathies, Sickle Cell Disease, Thalassemia
Being tested: Busulfex, Fludarabine, Alemtuzumab, Stem Cell Transfusion
Keywords: Hemoglobinopathies, Sickle cell anemia, sickle cell-hemoglobin C disease, sickle cell-B-thalassemia, transfusion-dependant thalassemia, allogeneic transplant, nonmyeloablative transplant, Stem cell transfusion, graft vs. host disease
Medical subject headings: Hemoglobinopathies, Anemia, Sickle Cell, Thalassemia, Hemoglobin SC Disease, Graft vs Host Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BusulfexDrug
Given once daily for 4 days
FludarabineDrug
Given intravenously once daily for 4 days
AlemtuzumabDrug
Also called CAMPATH
One day before fludarabine and busulfex are started, alemtuzumab will be given once daily for 5 days.
Stem Cell TransfusionProcedure or surgery
Performed three days after the end of chemotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

Stable Engraftment With Donor Stem Cells in Patients With Severe Hemoglobinopathy.
Outcome was measured by ANC >500 for three consecutive days prior to day 30 after PBSC infusion, >25% of hematopoietic cells are donor derived as determined by molecular chimerism assays or cytogenetic methods prior to day 45 after PBSC infusion and >25% of hematopoietic cells are donor derived as determined by molecular chimerism assays or cytogenetic methods after day 180 after PBSC infusion.
Measured: 3 years

Secondary outcomes (2)

Solid Organ Toxicity Related to the Conditioning Regimen.
Outcome was measured by the assessment of organ toxicity related to Busulfex, fludarabine and alemtuzumab.
Measured: 3 years
The Incidence of Grade II-IV Acute Graft vs. Host Disease.
Outcome was measured by incidence and severity of acute and chronic GVHD following donor stem cell infusion.
Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2004Jul 2009

First posted12 Sep 2005 (estimated)
Study startMar 2004
Primary completionMar 2008
Study completionJul 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HemoglobinopathiesStudies of the same condition, open and under way.
More trials run by Dana-Farber Cancer InstituteThe 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 2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 2 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00153985
Sponsor's protocol ID: 03-338
Status last verified: Jul 2013
First submitted: 8 Sep 2005
Last updated: 30 Jul 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Armistead PM, Mohseni M, Gerwin R, Walsh EC, Iravani M, Chahardouli B, Rostami S, Zhang W, Neuberg D, Rioux J, Ghavamzadeh A, Ritz J, Antin JH, Wu CJ. Erythroid-lineage-specific engraftment in patients with severe hemoglobinopathy following allogeneic hematopoietic stem cell transplantation. Exp Hematol. 2008 Sep;36(9):1205-15. doi: 10.1016/j.exphem.2008.04.004. Epub 2008 Jun 11.
PubMed 18550258

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 1/2
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Long-term Mitapivat Dosing in Subjects With Stable Sickle Cell Disease: An Extension of a Phase I Pilot Study of Mitapivat
Sickle Cell Disease, Hemolytic Anemia
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
RecruitingPhase 1
Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects With Stable Sickle Cell Disease
Sickle Cell Disorders, Sickle Cell Disease
RecruitingPhase 4
Clinical and Biomarker Effects of Depot Medroxyprogesterone Acetate in Females With Sickle Cell Disease
Sickle Cell Disease (SCD), Vaso-Occlusive Pain Episode in Sickle Cell Disease
Active, not recruiting
Evaluation the Safety and Efficacy of KL003 Cell Injection in the Treatment of Transfusion-dependent β-thalassemia.
Transfusion-dependent Beta-Thalassemia

All Hemoglobinopathies trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Multi-Center Study Using Allogeneic Stem Cell Transplantation Following Reduced Intensity Chemotherapy in Patients With Hemoglobinopathies
ClinicalTrials.gov ID: NCT00153985
Acronym / sponsor ID: 03-338
Conditions: Hemoglobinopathies, Sickle Cell Disease, Thalassemia
Keywords: Hemoglobinopathies, Sickle cell anemia, sickle cell-hemoglobin C disease, sickle cell-B-thalassemia, transfusion-dependant thalassemia, allogeneic transplant, nonmyeloablative transplant, Stem cell transfusion
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 2 participants (actual)
Lead sponsor: Dana-Farber Cancer InstituteUniversity, hospital or other
Collaborators: Beth Israel Deaconess Medical Center, Massachusetts General Hospital, Brigham and Women's Hospital, Emory University, Feist-Weiller Cancer Center at Louisiana State University Health Sciences, Ohio State University
Study start: Mar 2004
Primary completion: Mar 2008 (actual)
Study completion: Jul 2009 (actual)
First posted: 12 Sep 2005 (estimated)
Results: Posted 12 Mar 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

In order to undergo transplant procedure, patients will be admitted to the hospital for approximately 10-14 days.
To prepare patient's bone marrow to accept donor stem cells, they will receive fludarabine and busulfex. Fludarabine will be given intravenously once daily for 4 days. Busulfex will be given once daily for the same 4 days.
One day before patients receive busulfex and fludarabine, they will also be given alemtuzumab intravenously once daily for 5 days.
Three days after the end of chemotherapy, patients will receive the infusion of donor stem cells.
If patients have thalassemia, they will receive subcutaneous injections of filgrastim starting on day one after the donor stem cell transfusion and will continue receiving filgrastim every day until it appears that the donor stem cells have been accepted. If the patient has sickle cell disease, filgrastim will not be given,
Additional drugs will be given to help prevent infection (i.e. antibiotics).
After stem cell infusion patients will be examined and have blood tests weekly for 1 month. Bone marrow biopsies, and blood work will also be performed 1 month, 3 months, 6 months and 1 year after stem cell infusion.
Patients will be on the study for about 12 months. After study is completed progress will be monitored on an annual basis.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

Patients with sickle cell disease should have one or more of the following: acute chest syndrome requiring hospitalization; nonhemorrhagic stroke or central nervous system event lasting longer than 24 hours; recurrent caso-occlusive pain or recurrent priapism; sickle neuropathy; bilateral proliferative retinopathy and major visual impairment of at least one eye; osteonecrosis of multiple joints; transfusion dependence; vaso-occlusive.
Patients with thalassemia should have one or more of the following: transfusion dependence; iron overload; presence of 2 or more alloantibodies against red cell antigens.

Key exclusion criteria (6 listed)

Pregnancy
Acute hepatitis
Cardiac ejection fraction < 30%
Severe renal impairment
Severe residual functional neurologic impairment

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
BusulfexGiven once daily for 4 days	Drug	–
FludarabineGiven intravenously once daily for 4 days	Drug	–
AlemtuzumabAlso: CAMPATHOne day before fludarabine and busulfex are started, alemtuzumab will be given once daily for 5 days.	Drug	–
Stem Cell TransfusionPerformed three days after the end of chemotherapy	Procedure or surgery	–

Primary outcome

Stable Engraftment With Donor Stem Cells in Patients With Severe Hemoglobinopathy.
Time frame: 3 years
Outcome was measured by ANC >500 for three consecutive days prior to day 30 after PBSC infusion, >25% of hematopoietic cells are donor derived as determined by molecular chimerism assays or cytogenetic methods prior to day 45 after PBSC infusion and >25% of hematopoietic cells are donor derived as determined by molecular chimerism assays or cytogenetic methods after day 180 after PBSC infusion.

2 secondary outcomes

Solid Organ Toxicity Related to the Conditioning Regimen.
Time frame: 3 years
The Incidence of Grade II-IV Acute Graft vs. Host Disease.
Time frame: 3 years

Results and safety

Results posted to the registry on 12 Mar 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Transplant for Severe Hemoglobinopathies	2	2

Primary outcome: Stable Engraftment With Donor Stem Cells in Patients With Severe Hemoglobinopathy.

Time frame: 3 years. Number. Unit: participants

Measure	Transplant for Severe Hemoglobinopathies n = 2
Value	2

Population analysed: All patients enrolled.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Through study completion in 2009 (or patient death). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Transplant for Severe Hemoglobinopathies	1 of 2 (50%)	1 of 2 (50%)	Not reported

Limitations and caveats (from the sponsor): Early termination leading to small numbers of subjects analyzed.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 18550258Armistead PM, Mohseni M, Gerwin R, Walsh EC, Iravani M, Chahardouli B, Rostami S, Zhang W, Neuberg D, Rioux J, Ghavamzadeh A, Ritz J, Antin JH, Wu CJ. Erythroid-lineage-specific engraftment in patients with severe hemoglobinopathy following allogeneic hematopoietic stem cell transplantation. Exp Hematol. 2008 Sep;36(9):1205-15. doi: 10.1016/j.exphem.2008.04.004. Epub 2008 Jun 11.

Related trials for Hemoglobinopathies

Active, not recruitingPhase 1/2
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Long-term Mitapivat Dosing in Subjects With Stable Sickle Cell Disease: An Extension of a Phase I Pilot Study of Mitapivat
Sickle Cell Disease, Hemolytic Anemia
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
RecruitingPhase 1
Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects With Stable Sickle Cell Disease
Sickle Cell Disorders, Sickle Cell Disease
RecruitingPhase 4
Clinical and Biomarker Effects of Depot Medroxyprogesterone Acetate in Females With Sickle Cell Disease
Sickle Cell Disease (SCD), Vaso-Occlusive Pain Episode in Sickle Cell Disease
Active, not recruiting
Evaluation the Safety and Efficacy of KL003 Cell Injection in the Treatment of Transfusion-dependent β-thalassemia.
Transfusion-dependent Beta-Thalassemia

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.

Catherine J. Wu, MD principal investigator

Dana-Farber Cancer Institute

6 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Busulfex, Fludarabine and Alemtuzumab in people with Hemoglobinopathies and Sickle Cell Disease, run by Dana-Farber Cancer Institute at 6 sites 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 2 inclusion and 6 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 30 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Mar 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Stable Engraftment With Donor Stem Cells in Patients With Severe Hemoglobinopathy. (time frame: 3 years). 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 NCT00153985, which also lists 1 linked publication.

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 30 Jul 2013.