Sickle Cell DiseasePhase 1/2NCT02435901
HSCT For Patients With High Risk Hemoglobinopathies Using Reduced Intensity
A Phase 1/2 study testing alemtuzumab (Campath IH), Fludarabine and Melphalan in people with Sickle Cell Disease and Beta Thalassemia-Major, run by Northwell Health at 1 site in United States.
Trial summary
This study will evaluate the use of reduced intensity conditioning regimen in patients with high risk hemoglobinopathy Sickle Cell and B-Thalassemia Major in combination with standard immunosuppressive medications, followed by a routine stem cell transplant in order to assess whether or not it is as effective as… Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- Sickle Cell Disease, Beta Thalassemia-Major
- What is being tested?
- alemtuzumab (Campath IH), Fludarabine and Melphalan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2008to Dec 2019
- Phase
- Phase 1/2
- 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 1 year to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patient Inclusion Criteria for Sickle Cell Disease
- Patients at least one year of age to less than or equal to 21 years of age with (Sickle Cell Disease-SS or Sickle Cell-S-β-Thalassemia and with one or more of the following disease complications:
- Development of stroke on chronic transfusion protocol.
- Allosensitization on chronic transfusion therapy
- Impaired neuropsychological function and abnormal MRI scan
- Abnormal Transcranial Doppler studies
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- Acute chest syndrome (2 to 3 episodes of acute chest syndrome in last 3 to 4 years).
- Ferritin level < 1500 mg/ml
- Recurrent painful priapism; 3-4 episodes/year requiring intervention.
- Recurrent vaso-occlusive crisis of at least 3 to 4 episodes/year.
- Osteonecrosis of multiple bones with documented destructive changes.
- Signed informed consent
- Patients physically and psychologically capable of undergoing transplantation and a period of strict isolation.
- Ferritin < 1500
- Liver Iron Concentration < 6mg/g
- Patient Inclusion Criteria for β Thalassemia major Patients less than or equal to 21 years of age with B- Thalassemia major on routine monthly transfusion protocol or with one or more of the following complications;
- Hepatomegaly.
- Liver biopsy revealing evidence of portal fibrosis as A) Mild B) Moderate
- Ferritin level≤ 1500ng/ml
- Liver Iron Concentration (LIC) < 6mg/g
Who cannot join
- Exclusion Criteria for Both Sickle Cell and β Thalassemia Major Patient
- HIV positive result confirmed by Western Blot.
- Pregnancy (Pregnancy testing for females of child-bearing age will be performed and those with a positive serum β-Human Chorionic Gonadotropin will be excluded) and lactating females.
- Creatinine greater than two times the upper limit of normal for the laboratory,
- Pulmonary disease with FVC, FEV1 or DLCO parameters < 50% predicted (corrected for hemoglobin) or stage 3 or 4 sickle lung disease.
- Cardiac insufficiency or coronary artery disease requiring treatment
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- Active infection requiring systemic antibiotic therapy with antibacterial, antifungal or antiviral agents
- Lansky performance score <70%- (Appendix B)
- Acute hepatitis/biopsy evidence of cirrhosis.
- Pulmonary Hypertension
Trial locations and contacts
1 site in 1 country.
United States1 site
Cohen Children's Medical Center of New York
New Hyde Park, New York, 11040
About this study
Official title: ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT) IN PATIENTS WITH HIGH RISK HEMOGLOBINOPATHIES LIKE SICKLE CELL DISEASE AND β-THALESSEMIA-MAJOR USING REDUCED INTENSITY CONDITIONING REGIMEN
This study will evaluate the use of reduced intensity conditioning regimen in patients with high risk hemoglobinopathy Sickle Cell and B-Thalassemia Major in combination with standard immunosuppressive medications, followed by a routine stem cell transplant in order to assess whether or not it is as effective as myeloablative high dose chemotherapy and transplant.
Read the detailed description
Standard myeloablative regimens are toxic to non-hematopoietic tissue and are associated with treatment related mortality and morbidity (TRM). Preparative regimens that are not myeloablative are associated with a greatly decreased incidence of TRM. In addition to providing a less toxic regimen, the reduced intensity chemotherapy preparative regimen also remains immunosuppressive enough to allow donor engraftment. Recent report of non-myeloablative regimens which resulted in engraftment of allogeneic stem cell in hematological malignancies raises the possibility that this conditioning regimen might be useful in achieving engraftment in non hematological disorder.
In an effort to achieve stable engraftment with any suitable donor stem cell source and to minimize toxicity the investigators have developed a new reduced intensity conditioning regimen for high risk hemoglobinopathies with the main aim of significantly suppressing the recipient's immune system and facilitate engraftment.
Non-myeloablative or reduced-intensity immunosuppressive preparative regimens have achieved a stable, mixed chimerism engraftment and successful allogeneic bone marrow transplants.
- Conditions
- Sickle Cell Disease, Beta Thalassemia-Major
- Being tested
- alemtuzumab (Campath IH), Fludarabine, Melphalan, Cyclosporine, Mycophenolate mofetil
- Keywords
- Reduced Intensity Conditioning Regimen
- Medical subject headings
- Anemia, Sickle Cell, beta-Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
alemtuzumab (Campath IH)Drug
Also called Campath-IH
Alemtuzumab (Campath IH) is given daily over first 4 days, Day -20 to Day -17
FludarabineDrug
Fludarabine 35/m2 is given daily over 4 days on Day -7 to Day -4.
MelphalanDrug
Melphalan 70mg/m2 is given daily over 2 days on Day -3 to Day -2.
CyclosporineDrug
Immunosuppressant to prevent graft vs host disease is given on Day -1 prior to stem cell infusion
Immunosuppressant to prevent graft vs host disease is given on Day -1.
TacrolimusDrug
Immunosuppressant to prevent graft vs host disease is given Day -1 prior to stem cell infusion
Hematopoietic Stem Cell TransplantationBiological
Human Leukocyte Antigen (HLA) matched or mismatched; related or unrelated hematopoietic stem cells to be transplanted on Day 0.
| Study group | Role | What they receive |
|---|---|---|
| Reduced Intensity Regimen | Experimental | Administration of reduced doses of alemtuzumab (Campath-IH) IV 3mg test dose on Day -20 followed by daily dose of 10mg/dose on Day -19 to Day -17 for patients <10yrs or a daily dose of 15mg/dose on Day -19 to Day -17 for patients > 10yrs. Fludarabine 35mg/m2 daily for 4 days on Day -7 to Day -4. Melphalan 70mg/m2 daily for 2 days on Day -3 and Day -2. On Day -1 Cyclosporine OR Tacrolimus will be initiated along with Mycophenolate Mofetil as a graft vs host disease prophylaxis. On Day 0 the Human Leukocyte Antigen (HLA) matched or mismatched Hematopoietic Stem Cells from either the related or unrelated donor will be infused. Receives: Drug: alemtuzumab (Campath IH); Drug: Fludarabine; Drug: Melphalan; Drug: Cyclosporine; Drug: Mycophenolate mofetil; Drug: Tacrolimus; Biological: Hematopoietic Stem Cell Transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Sustained Cell Engraftment of Donor Cells
Sustained stem cell engraftment of donor cells will be evaluated by chimerism (FISH fluorescence in situ hybridization OR VNTR (Variable Number of Tandem Repeats), based on recipient/donor gender, at 30 days, 100 days, 6 months and 1 year following the use of reduced intensity conditioning.
Measured: 1 year
Secondary outcomes (2)
Assessment of Treatment Related Mortality and Morbidity
Patients will be evaluated for incidence and severity of graft versus host disease, infection, and cardiopulmonary complications.
Measured: 2 years
Event Free Survival; Number of Participants Who Survived at 2 Years
29 participants will be evaluated for Event Free Survival.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2015 (estimated)
- Study startDec 2008
- Primary completionMar 2019
- Study completionDec 2019
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 Sickle Cell DiseaseStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwell Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02435901
- Sponsor's protocol ID
- 08057
- Status last verified
- Jul 2021
- First submitted
- 24 Apr 2015
- Last updated
- 24 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Outcome data to include study findings.
Publications
King AA, Kamani N, Bunin N, Sahdev I, Brochstein J, Hayashi RJ, Grimley M, Abraham A, Dioguardi J, Chan KW, Douglas D, Adams R, Andreansky M, Anderson E, Gilman A, Chaudhury S, Yu L, Dalal J, Hale G, Cuvelier G, Jain A, Krajewski J, Gillio A, Kasow KA, Delgado D, Hanson E, Murray L, Shenoy S. Successful matched sibling donor marrow transplantation following reduced intensity conditioning in children with hemoglobinopathies. Am J Hematol. 2015 Dec;90(12):1093-8. doi: 10.1002/ajh.24183. Epub 2015 Oct 6.
PubMed 26348869
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT) IN PATIENTS WITH HIGH RISK HEMOGLOBINOPATHIES LIKE SICKLE CELL DISEASE AND β-THALESSEMIA-MAJOR USING REDUCED INTENSITY CONDITIONING REGIMEN
- ClinicalTrials.gov ID
- NCT02435901
- Acronym / sponsor ID
- 08057
- Conditions
- Sickle Cell Disease, Beta Thalassemia-Major
- Keywords
- Reduced Intensity Conditioning Regimen
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Northwell HealthUniversity, hospital or other
- Study start
- Dec 2008
- Primary completion
- Mar 2019 (actual)
- Study completion
- Dec 2019 (actual)
- First posted
- 6 May 2015 (estimated)
- Results
- Posted 5 Nov 2020
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 evaluate the use of reduced intensity conditioning regimen in patients with high risk hemoglobinopathy Sickle Cell and B-Thalassemia Major in combination with standard immunosuppressive medications, followed by a routine stem cell transplant in order to assess whether or not it is as effective as myeloablative high dose chemotherapy and transplant.
Detailed description
Standard myeloablative regimens are toxic to non-hematopoietic tissue and are associated with treatment related mortality and morbidity (TRM). Preparative regimens that are not myeloablative are associated with a greatly decreased incidence of TRM. In addition to providing a less toxic regimen, the reduced intensity chemotherapy preparative regimen also remains immunosuppressive enough to allow donor engraftment. Recent report of non-myeloablative regimens which resulted in engraftment of allogeneic stem cell in hematological malignancies raises the possibility that this conditioning regimen might be useful in achieving engraftment in non hematological disorder.
In an effort to achieve stable engraftment with any suitable donor stem cell source and to minimize toxicity the investigators have developed a new reduced intensity conditioning regimen for high risk hemoglobinopathies with the main aim of significantly suppressing the recipient's immune system and facilitate engraftment.
Non-myeloablative or reduced-intensity immunosuppressive preparative regimens have achieved a stable, mixed chimerism engraftment and successful allogeneic bone marrow transplants.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Reduced Intensity Regimen | Experimental | Drug: alemtuzumab (Campath IH), Drug: Fludarabine, Drug: Melphalan, Drug: Cyclosporine, Drug: Mycophenolate mofetil, Drug: Tacrolimus, Biological: Hematopoietic Stem Cell TransplantationAdministration of reduced doses of alemtuzumab (Campath-IH) IV 3mg test dose on Day -20 followed by daily dose of 10mg/dose on Day -19 to Day -17 for patients <10yrs or a daily dose of 15mg/dose on Day -19 to Day -17 for patients > 10yrs. Fludarabine 35mg/m2 daily for 4 days on Day -7 to Day -4. Melphalan 70mg/m2 daily for 2 days on Day -3 and Day -2. On Day -1 Cyclosporine OR Tacrolimus will be initiated along with Mycophenolate Mofetil as a graft vs host disease prophylaxis. On Day 0 the Human Leukocyte Antigen (HLA) matched or mismatched Hematopoietic Stem Cells from either the related or unrelated donor will be infused. |
Who may qualify
- Ages
- 1 year to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (20 listed)
- Patient Inclusion Criteria for Sickle Cell Disease
- Patients at least one year of age to less than or equal to 21 years of age with (Sickle Cell Disease-SS or Sickle Cell-S-β-Thalassemia and with one or more of the following disease complications:
- Development of stroke on chronic transfusion protocol.
- Allosensitization on chronic transfusion therapy
- Impaired neuropsychological function and abnormal MRI scan
Key exclusion criteria (10 listed)
- Exclusion Criteria for Both Sickle Cell and β Thalassemia Major Patient
- HIV positive result confirmed by Western Blot.
- Pregnancy (Pregnancy testing for females of child-bearing age will be performed and those with a positive serum β-Human Chorionic Gonadotropin will be excluded) and lactating females.
- Creatinine greater than two times the upper limit of normal for the laboratory,
- Pulmonary disease with FVC, FEV1 or DLCO parameters < 50% predicted (corrected for hemoglobin) or stage 3 or 4 sickle lung disease.
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 |
|---|---|---|
| alemtuzumab (Campath IH)Also: Campath-IHAlemtuzumab (Campath IH) is given daily over first 4 days, Day -20 to Day -17 | Drug | Reduced Intensity Regimen |
| FludarabineFludarabine 35/m2 is given daily over 4 days on Day -7 to Day -4. | Drug | Reduced Intensity Regimen |
| MelphalanMelphalan 70mg/m2 is given daily over 2 days on Day -3 to Day -2. | Drug | Reduced Intensity Regimen |
| CyclosporineImmunosuppressant to prevent graft vs host disease is given on Day -1 prior to stem cell infusion | Drug | Reduced Intensity Regimen |
| Mycophenolate mofetilImmunosuppressant to prevent graft vs host disease is given on Day -1. | Drug | Reduced Intensity Regimen |
| TacrolimusImmunosuppressant to prevent graft vs host disease is given Day -1 prior to stem cell infusion | Drug | Reduced Intensity Regimen |
| Hematopoietic Stem Cell TransplantationHuman Leukocyte Antigen (HLA) matched or mismatched; related or unrelated hematopoietic stem cells to be transplanted on Day 0. | Biological | Reduced Intensity Regimen |
Primary outcome
Number of Participants With Sustained Cell Engraftment of Donor Cells
Time frame: 1 year
Sustained stem cell engraftment of donor cells will be evaluated by chimerism (FISH fluorescence in situ hybridization OR VNTR (Variable Number of Tandem Repeats), based on recipient/donor gender, at 30 days, 100 days, 6 months and 1 year following the use of reduced intensity conditioning.
2 secondary outcomes
Assessment of Treatment Related Mortality and Morbidity
Time frame: 2 years
Event Free Survival; Number of Participants Who Survived at 2 Years
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26348869King AA, Kamani N, Bunin N, Sahdev I, Brochstein J, Hayashi RJ, Grimley M, Abraham A, Dioguardi J, Chan KW, Douglas D, Adams R, Andreansky M, Anderson E, Gilman A, Chaudhury S, Yu L, Dalal J, Hale G, Cuvelier G, Jain A, Krajewski J, Gillio A, Kasow KA, Delgado D, Hanson E, Murray L, Shenoy S. Successful matched sibling donor marrow transplantation following reduced intensity conditioning in children with hemoglobinopathies. Am J Hematol. 2015 Dec;90(12):1093-8. doi: 10.1002/ajh.24183. Epub 2015 Oct 6.
- Individual participant dataSharing planned: Yes. Outcome data to include study findings.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing alemtuzumab (Campath IH), Fludarabine and Melphalan in people with Sickle Cell Disease and Beta Thalassemia-Major, run by Northwell Health 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 20 inclusion and 10 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 24 Aug 2021. 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 combined 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.
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 5 Nov 2020). 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?
Number of Participants With Sustained Cell Engraftment of Donor Cells (time frame: 1 year). 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 NCT02435901, 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 24 Aug 2021.