Sickle Cell DiseasePhase 3NCT01877837
Stem Cell Transplantation for Sickle Cell Anemia
A Phase 3 study testing Alemtuzumab, Fludarabine and Melphalan in people with Sickle Cell Disease, run by Hackensack Meridian Health at 1 site in United States.
Trial summary
This protocol will be investigating the use of stem cell transplantation, in related donors, to cure sickle cell disease. Sickle cell disease is a recessive disorder caused by a point mutation that results in the substitution of valine for glutamic acid at the sixth position in the B-chain of hemoglobin. Read more about this study
- Who is it for?
- Ages 2 to 30 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Alemtuzumab, Fludarabine and Melphalan
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2011to Sep 2021
- Phase
- Phase 3
- 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 2 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patient Eligibility
- 1) Matched sibling donors (9-10/10 marrow/PBSC or 5-6/6 UCB (single or double) with a total TNC dose of greater than 5 x 107/kg recipient weight)
- Age 2-30
- Hb SS, S-thal0, S-thal+, SC
- Evidence of ongoing hemolysis: Hb<10, retic >5%, LDH > 500, TB>2
- Karnofsky/Lansky score >50
Show all 11Show fewer
- LVSF>26% or LVEF>40%
- DLCO >40% or O2 sat >85% for those patients that can't perform PFTs
- GFR >70 and serum creatinine < 1.5 * ULN for age
- ALT and AST < 5 x ULN, direct bilirubin <2 x ULN
- If the patient has been on chronic transfusion or has a ferritin >1000, liver biopsy should be done and show no evidence of bridging fibrosis or cirrhosis
Who cannot join
- Evidence of uncontrolled bacterial, viral, or fungal infection within one month prior to initiation of the conditioning regimen
- Pregnant or breastfeeding
- HIV positive
- Written informed consent not obtained
Trial locations and contacts
1 site in 1 country.
United States1 site
Hackensack University Medical Center
Hackensack, New Jersey, 07601
About this study
Official title: Reduced Intensity Matched Sibling Bone Marrow Transplantation for Sickle Cell Anemia in Patients 2-30 Years Old
This protocol will be investigating the use of stem cell transplantation, in related donors, to cure sickle cell disease. Sickle cell disease is a recessive disorder caused by a point mutation that results in the substitution of valine for glutamic acid at the sixth position in the B-chain of hemoglobin. This leads to sickling of the red blood cells under many conditions, such as hypoxia, dehydration, and hyperthermia. The sickling leads to vaso-occlusion, which causes irreversible damage in almost all systems in the body, including the central nervous system (CNS), lungs, heart, bones, eyes, liver, and kidneys.
Read the detailed description
Primary objective:
- To determine disease free survival (DFS) at two years after matched sibling transplant using bone marrow (BM) after a conditioning regimen consisting of distal timed Alemtuzumab, Fludarabine, and Melphalan for patients 2-30 y/o
Secondary objectives:
- Overall survival
- Rate of neutrophil and platelet engraftment for BM
- Incidence of graft failure
- Incidence of grade II-IV and grade III-IV acute graft vs host disease (GVHD)
- Incidence of chronic GVHD
- Incidence of other transplant complications, such as veno-occlusive disease, central nervous system (CNS) toxicity, and idiopathic pneumonia syndrome (IPS)
- Incidence of reactivation of CMV, EBV, adenovirus, BK/JC virus
- Incidence of invasive fungal disease
- Time to immune reconstitution via monitoring of lymphocyte subpopulations and immunoglobulin levels
- Conditions
- Sickle Cell Disease
- Being tested
- Alemtuzumab, Fludarabine, Melphalan, Stem Cells
- Keywords
- Stem cell transplant, Sickle cell, Stem cell transplantation, Related, Unrelated
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlemtuzumabDrug
Also called Alemtuzumab (Campath)
Adjusted Ideal Body Weight Formula: AIBW = IBW + [(0.4) x (ABW - IBW)]
- Medications i.) Alemtuzumab I. Hb S% must be < or = 45% within 7 days prior to initiation of Alemtuzumab II. Iron chelation and hydroxyurea must be discontinued >48 hours before initiating therapy III. Alemtuzumab will be diluted in 100mL of 0.9% NS and infused at a rate as below
FludarabineDrug
Also called Fludarabine (Fludara)
- Fludarabine should be diluted in 100 ml 0.9%NS and given over 30 minutes. II. A daily dose of an antiemetic should be given 30 minutes prior to administration of the Fludarabine
MelphalanDrug
Also called Melphalan (Alkeran)
- Melphalan should be diluted in 0.9%NS to a concentration of 0.1 -0.45 mg/mL and given over 45 minutes. *Entire dose must be infused within 60 minutes of reconstitution in Pharmacy.
II. A daily dose of an antiemetic should be given 30 minutes prior to administration of the Melphalan III. Patients should be encouraged to suck on a popsicle or something similar during the Melphalan infusion.
Stem CellsProcedure or surgery
Infusion of Hematopoietic Stem Cells
| Study group | Role | What they receive |
|---|---|---|
| Related donor | Experimental | Matched sibling donors (9-10/10 marrow/PBSC or 5-6/6 UCB (single) with a total TNC dose of greater than 5 x 107/kg recipient weight), age 2-30 years after conditioning regimen Alemtuzumab , Fludarabine, and Melphalan.
1) Patients will receive a conditioning regimen composed of Alemtuzumab, Fludarabine, and Melphalan as detailed in the table below.
Day Treatment
* -22 Alemtuzumab 3mg IV (test dose)
* -21 Alemtuzumab 10mg IV
* -20 Alemtuzumab 15mg IV
* -19 Alemtuzumab 20mg IV
* -8 Fludarabine 30mg/m2 IV
* -7 Fludarabine 30mg/m2 IV
* -6 Fludarabine 30mg/m2 IV
* -5 Fludarabine 30mg/m2 IV
* -4 Fludarabine 30mg/m2 IV
* -3 Melphalan 140mg/m2 IV
* -2 Rest Day
* -1 Rest Day
* 0 Stem Cell Infusion Receives: Drug: Alemtuzumab; Drug: Fludarabine; Drug: Melphalan; Procedure: Stem Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Graft Failure
Primary endpoint:
In each group, the Number of participants with Graft Failure at the 2 years endpoint will be estimated using the Kaplan Meier product limit estimator.
Measured: 2 years
Secondary outcomes (1)
Overall Survival
Secondary endpoints:
Overall survival: The distribution of time to death from any cause will be estimated by Kaplan- Meier product limit function and plotted. The overall survival will be measured from the time of transplant to any death and patients will be followed for 2 years.
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 posted14 Jun 2013 (estimated)
- Study startJun 2011
- Primary completionSep 2021
- Study completionSep 2021
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.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hackensack Meridian Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jennifer Krajewski, MD, Principal investigator, Hackensack Meridian Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01877837
- Sponsor's protocol ID
- Pro00001894
- Status last verified
- Oct 2022
- First submitted
- 12 Jun 2013
- Last updated
- 7 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reduced Intensity Matched Sibling Bone Marrow Transplantation for Sickle Cell Anemia in Patients 2-30 Years Old
- ClinicalTrials.gov ID
- NCT01877837
- Acronym / sponsor ID
- Pro00001894
- Conditions
- Sickle Cell Disease
- Keywords
- Stem cell transplant, Sickle cell, Stem cell transplantation, Related, Unrelated
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Hackensack Meridian HealthUniversity, hospital or other
- Study start
- Jun 2011
- Primary completion
- Sep 2021 (actual)
- Study completion
- Sep 2021 (actual)
- First posted
- 14 Jun 2013 (estimated)
- Results
- Posted 7 Nov 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This protocol will be investigating the use of stem cell transplantation, in related donors, to cure sickle cell disease. Sickle cell disease is a recessive disorder caused by a point mutation that results in the substitution of valine for glutamic acid at the sixth position in the B-chain of hemoglobin. This leads to sickling of the red blood cells under many conditions, such as hypoxia, dehydration, and hyperthermia. The sickling leads to vaso-occlusion, which causes irreversible damage in almost all systems in the body, including the central nervous system (CNS), lungs, heart, bones, eyes, liver, and kidneys.
Detailed description
Primary objective:
- To determine disease free survival (DFS) at two years after matched sibling transplant using bone marrow (BM) after a conditioning regimen consisting of distal timed Alemtuzumab, Fludarabine, and Melphalan for patients 2-30 y/o
Secondary objectives:
- Overall survival
- Rate of neutrophil and platelet engraftment for BM
- Incidence of graft failure
- Incidence of grade II-IV and grade III-IV acute graft vs host disease (GVHD)
- Incidence of chronic GVHD
- Incidence of other transplant complications, such as veno-occlusive disease, central nervous system (CNS) toxicity, and idiopathic pneumonia syndrome (IPS)
- Incidence of reactivation of CMV, EBV, adenovirus, BK/JC virus
- Incidence of invasive fungal disease
- Time to immune reconstitution via monitoring of lymphocyte subpopulations and immunoglobulin levels
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Related donor | Experimental | Drug: Alemtuzumab, Drug: Fludarabine, Drug: Melphalan, Procedure: Stem CellsMatched sibling donors (9-10/10 marrow/PBSC or 5-6/6 UCB (single) with a total TNC dose of greater than 5 x 107/kg recipient weight), age 2-30 years after conditioning regimen Alemtuzumab , Fludarabine, and Melphalan. 1) Patients will receive a conditioning regimen composed of Alemtuzumab, Fludarabine, and Melphalan as detailed in the table below. Day Treatment * -22 Alemtuzumab 3mg IV (test dose) * -21 Alemtuzumab 10mg IV * -20 Alemtuzumab 15mg IV * -19 Alemtuzumab 20mg IV * -8 Fludarabine 30mg/m2 IV * -7 Fludarabine 30mg/m2 IV * -6 Fludarabine 30mg/m2 IV * -5 Fludarabine 30mg/m2 IV * -4 Fludarabine 30mg/m2 IV * -3 Melphalan 140mg/m2 IV * -2 Rest Day * -1 Rest Day * 0 Stem Cell Infusion |
Who may qualify
- Ages
- 2 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (11 listed)
- Patient Eligibility
- 1) Matched sibling donors (9-10/10 marrow/PBSC or 5-6/6 UCB (single or double) with a total TNC dose of greater than 5 x 107/kg recipient weight)
Key exclusion criteria (4 listed)
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 |
|---|---|---|
| AlemtuzumabAlso: Alemtuzumab (Campath)Adjusted Ideal Body Weight Formula: AIBW = IBW + [(0.4) x (ABW - IBW)] b) Medications i.) Alemtuzumab I. Hb S% must be < or = 45% within 7 days prior to initiation of Alemtuzumab II. Iron chelation and hydroxyurea must be discontinued >48 hours before initiating therapy III. Alemtuzumab will be diluted in 100mL of 0.9% NS and infused at a rate as below | Drug | Related donor |
| FludarabineAlso: Fludarabine (Fludara)I. Fludarabine should be diluted in 100 ml 0.9%NS and given over 30 minutes. II. A daily dose of an antiemetic should be given 30 minutes prior to administration of the Fludarabine | Drug | Related donor |
| MelphalanAlso: Melphalan (Alkeran)I. Melphalan should be diluted in 0.9%NS to a concentration of 0.1 -0.45 mg/mL and given over 45 minutes. *Entire dose must be infused within 60 minutes of reconstitution in Pharmacy. II. A daily dose of an antiemetic should be given 30 minutes prior to administration of the Melphalan III. Patients should be encouraged to suck on a popsicle or something similar during the Melphalan infusion. | Drug | Related donor |
| Stem CellsInfusion of Hematopoietic Stem Cells | Procedure or surgery | Related donor |
Primary outcome
Number of Participants With Graft Failure
Time frame: 2 years
Primary endpoint: In each group, the Number of participants with Graft Failure at the 2 years endpoint will be estimated using the Kaplan Meier product limit estimator.
1 secondary outcome
Overall Survival
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 7 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Jennifer Krajewski, MD principal investigator
Hackensack Meridian Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Alemtuzumab, Fludarabine and Melphalan in people with Sickle Cell Disease, run by Hackensack Meridian 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 11 inclusion and 4 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 7 Nov 2022. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 7 Nov 2022). 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 Graft Failure (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Nov 2022.