Abatacept for GVHD Prophylaxis After Hematopoietic Stem Cell Transplantation for Pediatric Sickle Cell Disease
NCT ID: NCT02867800
Last Updated: 2024-06-13
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1
24 participants
INTERVENTIONAL
2016-07-31
2023-12-30
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Standard GVHD Prophylaxis + Abatacept
Subjects will receive
* premedication (Diphenhydramine, Acetaminophen, Methylprednisolone; and Meperidine as needed)
* immunosuppression (Alemtuzumab, or Thymoglobulin)
* conditioning regimen (Fludarabine, Thiotepa, and Melphalan)
* GVHD prophylaxis: calcineurin inhibitor (Cyclosporine,Tacrolimus, Sirolimus or Mycophenolate Mofetil with permission of the sponsor) and Methotrexate plus Abatacept on days -1, +5, +14 and +28, and a marrow infusion on day 0.
Diphenhydramine
(Standard of Care) Premedication
Diphenhydramine: 1 mg/kg IV or PO q 8 hours (maximum=50 mg)
Acetaminophen
(Standard of Care) Premedication
Acetaminophen: 10-15 mg/kg PO q 6 hours (maximum=1000 mg)
Methylprednisolone
(Standard of Care) Premedication
Methylprednisolone: 0.25-0.5 mg/kg IV q 6 hours
Meperidine
(Standard of Care) Premedication
Use as needed (PRN) Meperidine: 0.5 mg/kg IV q 4-6 hours (for rigors)
Alemtuzumab
(Standard of Care) Immunosuppression
Alemtuzumab:
A test dose of alemtuzumab, 3 mg, should be administered IV over 2 hours the first day. If the test dose is tolerated, administration of three treatment doses should begin within 24 hours. The three treatment doses should be administered on consecutive days. 10 mg/m2 should be given the first day, 15 mg/m2 the second and 20 mg/m2 the third.
Thymoglobulin
(Standard of Care) Immunosuppression
Thymoglobulin: A 4 mg/kg dose of anti-thymocyte globulin should be administered in place of each alemtuzumab dose not completed.
Fludarabine
(Standard Conditioning Regimen)
Fludarabine should be administered 30 mg/m2 IV daily for five days. It should be infused over 30 to 60 minutes.
Melphalan
(Standard Conditioning Regimen)
Melphalan should be administered 140 mg/m2 IV 3 days before marrow infusion. It should be infused within 60 minutes of preparation and over a maximum of 30 minutes. It should be infused immediately after the fludarabine infusion is complete.
Thiotepa
(Standard Conditioning Regimen)
Thiotepa should be administered 8 mg/kg IV 3 days before marrow infusion. It should be infused immediately after the fludarabine infusion is complete. The thiotepa should be infused over one hour.
Cyclosporine
(Standard GVHD Prophylaxis) Calcineurin inhibitor
Cyclosporine: Administration will commence no later than at least 36 hours before marrow infusion; Cyclosporine doses will be adjusted to maintain a level of 150-300 ng/ml.
Tacrolimus
(Standard GVHD Prophylaxis) Calcineurin inhibitor
Tacrolimus: Administration will commence no later than at least 36 hours before marrow infusion; Tacrolimus doses will be adjusted to maintain a level of 8-15 ng/ml.
Methotrexate
(Standard GVHD Prophylaxis)
Methotrexate will be given at a dose of 15 mg/m2 IV on day 1 and a dose of 10 mg/m2 IV on days 3, 6 and 11. Dosing shall be based on actual weight.
Abatacept
(Investigational)
Abatacept will be administered intravenously at a dose of 10 mg/kg based on actual weight with a maximum of 750 mg. In cases where the calculated dose is less than or equal to 110% of a simple multiple of a 250 mg vial: 250 mg (275mg), 500 mg (550 mg) or 750 mg (825 mg), the dose may be rounded down to the nearest multiple. No rounding up of the abatacept dose is permitted.
Marrow infusion
(Standard)
A procedure that infuses healthy cells, called stem cells, into your body to replace damaged or diseased bone marrow. A bone marrow transplant may also be used to treat certain types of cancer
Sirolimus
(Standard GVHD Prophylaxis)
Calcineurin inhibitor (cyclosporine or tacrolimus or with permission of the sponsor: sirolimus or mycophenolate mofetil (MMF)) administration will commence no later than day -2 (at least 36 hours before the stem cell infusion); cyclosporine doses will be adjusted to maintain a level of 150-300 ng/ml. This range assumes monitoring by mass spectrometry. If an immunoassay is used instead, the equivalent range for that immunoassay should be used.
Mycophenolate Mofetil
(Standard GVHD Prophylaxis)
Calcineurin inhibitor (cyclosporine or tacrolimus or with permission of the sponsor: sirolimus or mycophenolate mofetil (MMF)) administration will commence no later than day -2 (at least 36 hours before the stem cell infusion); cyclosporine doses will be adjusted to maintain a level of 150-300 ng/ml. This range assumes monitoring by mass spectrometry. If an immunoassay is used instead, the equivalent range for that immunoassay should be used.
Interventions
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Diphenhydramine
(Standard of Care) Premedication
Diphenhydramine: 1 mg/kg IV or PO q 8 hours (maximum=50 mg)
Acetaminophen
(Standard of Care) Premedication
Acetaminophen: 10-15 mg/kg PO q 6 hours (maximum=1000 mg)
Methylprednisolone
(Standard of Care) Premedication
Methylprednisolone: 0.25-0.5 mg/kg IV q 6 hours
Meperidine
(Standard of Care) Premedication
Use as needed (PRN) Meperidine: 0.5 mg/kg IV q 4-6 hours (for rigors)
Alemtuzumab
(Standard of Care) Immunosuppression
Alemtuzumab:
A test dose of alemtuzumab, 3 mg, should be administered IV over 2 hours the first day. If the test dose is tolerated, administration of three treatment doses should begin within 24 hours. The three treatment doses should be administered on consecutive days. 10 mg/m2 should be given the first day, 15 mg/m2 the second and 20 mg/m2 the third.
Thymoglobulin
(Standard of Care) Immunosuppression
Thymoglobulin: A 4 mg/kg dose of anti-thymocyte globulin should be administered in place of each alemtuzumab dose not completed.
Fludarabine
(Standard Conditioning Regimen)
Fludarabine should be administered 30 mg/m2 IV daily for five days. It should be infused over 30 to 60 minutes.
Melphalan
(Standard Conditioning Regimen)
Melphalan should be administered 140 mg/m2 IV 3 days before marrow infusion. It should be infused within 60 minutes of preparation and over a maximum of 30 minutes. It should be infused immediately after the fludarabine infusion is complete.
Thiotepa
(Standard Conditioning Regimen)
Thiotepa should be administered 8 mg/kg IV 3 days before marrow infusion. It should be infused immediately after the fludarabine infusion is complete. The thiotepa should be infused over one hour.
Cyclosporine
(Standard GVHD Prophylaxis) Calcineurin inhibitor
Cyclosporine: Administration will commence no later than at least 36 hours before marrow infusion; Cyclosporine doses will be adjusted to maintain a level of 150-300 ng/ml.
Tacrolimus
(Standard GVHD Prophylaxis) Calcineurin inhibitor
Tacrolimus: Administration will commence no later than at least 36 hours before marrow infusion; Tacrolimus doses will be adjusted to maintain a level of 8-15 ng/ml.
Methotrexate
(Standard GVHD Prophylaxis)
Methotrexate will be given at a dose of 15 mg/m2 IV on day 1 and a dose of 10 mg/m2 IV on days 3, 6 and 11. Dosing shall be based on actual weight.
Abatacept
(Investigational)
Abatacept will be administered intravenously at a dose of 10 mg/kg based on actual weight with a maximum of 750 mg. In cases where the calculated dose is less than or equal to 110% of a simple multiple of a 250 mg vial: 250 mg (275mg), 500 mg (550 mg) or 750 mg (825 mg), the dose may be rounded down to the nearest multiple. No rounding up of the abatacept dose is permitted.
Marrow infusion
(Standard)
A procedure that infuses healthy cells, called stem cells, into your body to replace damaged or diseased bone marrow. A bone marrow transplant may also be used to treat certain types of cancer
Sirolimus
(Standard GVHD Prophylaxis)
Calcineurin inhibitor (cyclosporine or tacrolimus or with permission of the sponsor: sirolimus or mycophenolate mofetil (MMF)) administration will commence no later than day -2 (at least 36 hours before the stem cell infusion); cyclosporine doses will be adjusted to maintain a level of 150-300 ng/ml. This range assumes monitoring by mass spectrometry. If an immunoassay is used instead, the equivalent range for that immunoassay should be used.
Mycophenolate Mofetil
(Standard GVHD Prophylaxis)
Calcineurin inhibitor (cyclosporine or tacrolimus or with permission of the sponsor: sirolimus or mycophenolate mofetil (MMF)) administration will commence no later than day -2 (at least 36 hours before the stem cell infusion); cyclosporine doses will be adjusted to maintain a level of 150-300 ng/ml. This range assumes monitoring by mass spectrometry. If an immunoassay is used instead, the equivalent range for that immunoassay should be used.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
(a) Patients falling into one of the following three groups will be considered to be at increased risk for GVHD:
(i) Are between 10 and 20.99 years and receiving their transplant from an HLA matched related donor.
(ii) Are between 3 and 9.99 years and receiving their transplant from an HLA matched related donor who is at least 10 years.
(iii) Are between 3 and 20.99 years and receiving their transplant from an HLA matched unrelated donor. Donors must be matched at the A, B, C and DRB1 loci at the allele level.
(b) Patients who meet one of the following criteria will qualify as having severe SCD:
(i) Previous clinical stroke, as evidenced by a neurological deficit lasting longer than 24 hours, which is accompanied by radiographic evidence of ischemic brain injury and cerebral vasculopathy.
(ii) Asymptomatic cerebrovascular disease, as evidenced by one the following:
* Progressive silent cerebral infarction, as evidenced by serial MRI scans that demonstrate the development of a succession of lesions (at least two temporally discreet lesions, each measuring at least 3 mm in greatest dimension on the most recent scan) or the enlargement of a single lesion, initially measuring at least 3 mm). Lesions must be visible on T2-weighted MRI sequences.
* Cerebral arteriopathy, as evidenced by abnormal transcranial doppler (TCD) testing (confirmed elevated velocities in any single vessel of time-averaged maximum mean velocities (TAMMV) \> 200 cm/sec for non-imaging TCD) or by significant vasculopathy on magnetic resonance angiogram (MRA) (greater than 50% stenosis of \> 2 arterial segments or complete occlusion of any single arterial segment).
(iii) Frequent ( ≥ 3 per year for preceding 2 years) painful vaso-occlusive episodes (defined as episode lasting ≥ 4 hours and requiring hospitalization or outpatient treatment with parenteral opioids). If patient is on hydroxurea and its use has been associated with a decrease in the frequency of episodes, the frequency should be gauged from the 2 years prior to the start of this drug.
(iv) Recurrent ( ≥ 3 in lifetime) acute chest syndrome events which have necessitated erythrocyte transfusion therapy.
(v) Any combination of ≥ 3 acute chest syndrome episodes and vaso-occlusive pain episodes (defined as above) yearly for 3 years. If patient is on hydroxurea and its use has been associated with a decrease in the frequency of episodes, the frequency should be gauged from the 3 years prior to the start of this drug.
2. All patients and/or their parents or legal guardians must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
3. Must have been evaluated and adequately counseled regarding treatment options for severe SCD by a pediatric hematologist.
4. Because of the elective and non-urgent nature of hematopoietic stem cell transplantation (HSCT) for SCD, it is important that all patients and families be counseled regarding fertility preservation measures available to them. All patients and/or their parents or legal guardians must indicate on the consent and assent forms that they have received this counseling.
Exclusion Criteria
2. Parenchymal lung disease stemming from SCD or other process defined as a diffusing capacity of the lungs for carbon monoxide (DLCO) (corrected for hemoglobin) or forced vital capacity of less than 45% of predicted. Children unable to perform pulmonary function testing will be excluded if they require daytime oxygen supplementation.
3. Renal dysfunction with an estimated glomerular filtration rate (GFR) \< 50% of predicted normal for age.
4. Cardiac dysfunction with shortening fraction \< 25%.
5. Neurologic impairment other than hemiplegia, defined as full-scale IQ ≤70, quadriplegia or paraplegia, inability to ambulate, or any impairment resulting in decline of Lansky performance score to \< 70%.
6. Clinical stroke within 6 months of anticipated transplant.
7. Karnofsky or Lansky functional performance score \< 70%.
8. Patient is human immunodeficiency virus (HIV) infected.
9. Donor is HIV infected.
10. Donor has Hgb SS, SC or SB0 thalassemia.
11. Patient with unspecified chronic toxicity serious enough to detrimentally affect the patient's capacity to tolerate bone marrow transplantation.
12. Patient or patient's guardian(s) unable to understand the nature and risks inherent in the bone marrow transplant (BMT) process.
13. History of lack of compliance with medical care that would jeopardize transplant course.
14. Donor who for psychological, physiologic, or medical reasons is unable to tolerate a bone marrow harvest or receive general anesthesia.
15. Active viral, bacterial, fungal or protozoal infection.
16. Donor is pregnant.
17. Patient is pregnant.
3 Years
20 Years
ALL
No
Sponsors
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Monica Bhatia
OTHER
Responsible Party
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Monica Bhatia
Associate Professor of Pediatrics at the Columbia University Medical Center
Principal Investigators
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Monica Bhatia, MD
Role: STUDY_CHAIR
Columbia University
Locations
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Children's National Medical Center
Washington D.C., District of Columbia, United States
Children's Healthcare of Atlanta
Atlanta, Georgia, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States
Floating Hospital for Children at Tufts Medical Center
Boston, Massachusetts, United States
Columbia University Irving Medical Center
New York, New York, United States
North Carolina Cancer Hospital
Chapel Hill, North Carolina, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
Countries
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Other Identifiers
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AAAQ2350
Identifier Type: -
Identifier Source: org_study_id
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