Sickle Cell DiseasePhase 1NCT02867800
Abatacept for GVHD Prophylaxis After Hematopoietic Stem Cell Transplantation for Pediatric Sickle Cell Disease
A Phase 1 study testing Diphenhydramine, Acetaminophen and Methylprednisolone in people with Sickle Cell Disease and Graft Versus Host Disease, run by Monica Bhatia at 7 sites in United States.
Trial summary
To assess the tolerability of the costimulation blocking agent abatacept (CTLA4-Ig) when added to the standard graft versus host disease (GVHD) prophylaxis regimen of a calcineurin inhibitor and methotrexate in patients receiving early alemtuzumab followed by fludarabine, thiotepa, melphalan, and alemtuzumab for… Read more about this study
- Who is it for?
- Ages 3 to 20 years
- Conditions the study is for
- Sickle Cell Disease, Graft Versus Host Disease
- What is being tested?
- Diphenhydramine, Acetaminophen and Methylprednisolone
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 7 sitesUnited States
- Study dates
- Jul 2016to 30 Dec 2023
- 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 3 to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients with hemoglobin (Hgb) SS or SB0 thalassemia between the ages of 3 and 20.99 years who are at least 10 kg getting an human leukocyte antigen (HLA) matched bone marrow transplant, will be eligible if they are at increased risk for graft versus host disease (GVHD) and have severe SCD.
- Patients falling into one of the following three groups will be considered to be at increased risk for GVHD:
- Are between 10 and 20.99 years and receiving their transplant from an HLA matched related donor.
- Are between 3 and 9.99 years and receiving their transplant from an HLA matched related donor who is at least 10 years.
- 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.
- Patients who meet one of the following criteria will qualify as having severe SCD:
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- 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.
- 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).
- 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.
- Recurrent ( ≥ 3 in lifetime) acute chest syndrome events which have necessitated erythrocyte transfusion therapy.
- 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.
- 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.
- Must have been evaluated and adequately counseled regarding treatment options for severe SCD by a pediatric hematologist.
- 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.
Who cannot join
- Bridging (portal to portal) fibrosis or cirrhosis of the liver.
- 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.
- Renal dysfunction with an estimated glomerular filtration rate (GFR) < 50% of predicted normal for age.
- Cardiac dysfunction with shortening fraction < 25%.
- 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%.
- Clinical stroke within 6 months of anticipated transplant.
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- Karnofsky or Lansky functional performance score < 70%.
- Patient is human immunodeficiency virus (HIV) infected.
- Donor is HIV infected.
- Donor has Hgb SS, SC or SB0 thalassemia.
- Patient with unspecified chronic toxicity serious enough to detrimentally affect the patient's capacity to tolerate bone marrow transplantation.
- Patient or patient's guardian(s) unable to understand the nature and risks inherent in the bone marrow transplant (BMT) process.
- History of lack of compliance with medical care that would jeopardize transplant course.
- Donor who for psychological, physiologic, or medical reasons is unable to tolerate a bone marrow harvest or receive general anesthesia.
- Active viral, bacterial, fungal or protozoal infection.
- Donor is pregnant.
- Patient is pregnant.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
Floating Hospital for Children at Tufts Medical Center
Boston, Massachusetts, 02111
North Carolina Cancer Hospital
Chapel Hill, North Carolina, 27514
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Nationwide Children's Hospital
Columbus, Ohio, 43205
Columbia University Irving Medical Center
New York, New York, 10032
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: Abatacept for Graft Versus Host Disease Prophylaxis After Hematopoietic Stem Cell Transplantation for Pediatric Sickle Cell Disease: a Sickle Transplant Alliance for Research Trial
To assess the tolerability of the costimulation blocking agent abatacept (CTLA4-Ig) when added to the standard graft versus host disease (GVHD) prophylaxis regimen of a calcineurin inhibitor and methotrexate in patients receiving early alemtuzumab followed by fludarabine, thiotepa, melphalan, and alemtuzumab for conditioning.
Read the detailed description
Outcomes of hematopoietic stem cell transplantation (HSCT) for children and adolescents with sickle cell disease (SCD) have improved. Graft versus host disease (GVHD), however, remains a barrier to success. GVHD accounts for most of the transplant related mortality and much of the morbidity in this setting-in part through the injury it directly causes and in part through the deleterious effects of steroids and the other immunosuppressive agents used to prevent and treat it. The results of pre-clinical studies and a phase I clinical study in patients with hematologic malignancies suggest that the costimulation blocking agent CTLA4-Ig may hold promise an agent for GVHD prophylaxis. In the present trial, the investigators are assessing the tolerability of adding abatacept to standard GVHD prophylaxis-a calcineurin inhibitor and methotrexate-in pediatric SCD patients receiving early alemtuzumab (completed by day -18) followed by fludarabine, thiotepa, and melphalan for conditioning. This trial will provide the foundation for subsequent trials designed to test the long-term hypothesis that abatacept is a safe, steroid-sparing effective adjunct to standard GVHD prophylaxis in this setting.
- Conditions
- Sickle Cell Disease, Graft Versus Host Disease
- Being tested
- Diphenhydramine, Acetaminophen, Methylprednisolone, Meperidine, Alemtuzumab
- Keywords
- Sickle Cell Disease, Graft Versus Host Disease, Abatacept, Hematopoietic Stem Cell Transplantation
- Medical subject headings
- Anemia, Sickle Cell, Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DiphenhydramineDrug
Also called Benadryl
(Standard of Care) Premedication
Diphenhydramine: 1 mg/kg IV or PO q 8 hours (maximum=50 mg)
AcetaminophenDrug
Also called Tylenol
(Standard of Care) Premedication
Acetaminophen: 10-15 mg/kg PO q 6 hours (maximum=1000 mg)
Also called Medrol
(Standard of Care) Premedication
Methylprednisolone: 0.25-0.5 mg/kg IV q 6 hours
MeperidineDrug
Also called Demerol
(Standard of Care) Premedication
Use as needed (PRN) Meperidine: 0.5 mg/kg IV q 4-6 hours (for rigors)
AlemtuzumabDrug
Also called Lemtrada
(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.
ThymoglobulinDrug
Also called Genzyme
(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.
FludarabineDrug
Also called Fludara
(Standard Conditioning Regimen)
Fludarabine should be administered 30 mg/m2 IV daily for five days. It should be infused over 30 to 60 minutes.
MelphalanDrug
Also called Alkeran
(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.
ThiotepaDrug
Also called Thioplex
(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.
CyclosporineDrug
Also called Neoral
(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.
TacrolimusDrug
Also called Protopic
(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.
MethotrexateDrug
Also called Trexall
(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.
AbataceptDrug
Also called CTLA4-Ig, Orencia
(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 infusionProcedure or surgery
Also called stem cell transplant
(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
SirolimusDrug
Also called Rapamune
(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.
Also called MMF
(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.
| Study group | Role | What they receive |
|---|---|---|
| Standard GVHD Prophylaxis + Abatacept | Experimental | 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. Receives: Drug: Diphenhydramine; Drug: Acetaminophen; Drug: Methylprednisolone; Drug: Meperidine; Drug: Alemtuzumab; Drug: Thymoglobulin; Drug: Fludarabine; Drug: Melphalan; Drug: Thiotepa; Drug: Cyclosporine; Drug: Tacrolimus; Drug: Methotrexate; Drug: Abatacept; Procedure: Marrow infusion; Drug: Sirolimus; Drug: Mycophenolate Mofetil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients who tolerate abatacept
Patients will be deemed to be evaluable for tolerability if they received all prescribed doses of abatacept.
Abatacept will deemed to be tolerated, if no more than one dose is withheld per protocol stipulations, no death from an infection that occurs within 30 days of or develops post-transplant lymphoproliferative disease (PTLD) within 100 days of receiving the last prescribed dose of abatacept.
Measured: Within 100 days of receiving the last prescribed dose of abatacept
Secondary outcomes (2)
Bearman Scale Score of Regimen-Related Toxicity (RRT)
RRT will be assessed according to Bearman Scale.
Measured: Day 42 post-transplant
Number of infections
Infections will include viremia, posttransplant lymphoproliferative disease and immune reconstitution.
Measured: Up to 180 days post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2016 (estimated)
- Study startJul 2016
- Primary completion30 Dec 2021
- Study completion30 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Monica Bhatia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Monica Bhatia, Columbia University
- Investigators
- Monica Bhatia, MD, Study chair, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02867800
- Sponsor's protocol ID
- AAAQ2350
- Status last verified
- Jun 2024
- First submitted
- 11 Aug 2016
- Last updated
- 13 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Abatacept for Graft Versus Host Disease Prophylaxis After Hematopoietic Stem Cell Transplantation for Pediatric Sickle Cell Disease: a Sickle Transplant Alliance for Research Trial
- ClinicalTrials.gov ID
- NCT02867800
- Acronym / sponsor ID
- AAAQ2350
- Conditions
- Sickle Cell Disease, Graft Versus Host Disease
- Keywords
- Sickle Cell Disease, Graft Versus Host Disease, Abatacept, Hematopoietic Stem Cell Transplantation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Monica BhatiaUniversity, hospital or other
- Study start
- Jul 2016 (actual)
- Primary completion
- 30 Dec 2021 (actual)
- Study completion
- 30 Dec 2023 (actual)
- First posted
- 16 Aug 2016 (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.
To assess the tolerability of the costimulation blocking agent abatacept (CTLA4-Ig) when added to the standard graft versus host disease (GVHD) prophylaxis regimen of a calcineurin inhibitor and methotrexate in patients receiving early alemtuzumab followed by fludarabine, thiotepa, melphalan, and alemtuzumab for conditioning.
Detailed description
Outcomes of hematopoietic stem cell transplantation (HSCT) for children and adolescents with sickle cell disease (SCD) have improved. Graft versus host disease (GVHD), however, remains a barrier to success. GVHD accounts for most of the transplant related mortality and much of the morbidity in this setting-in part through the injury it directly causes and in part through the deleterious effects of steroids and the other immunosuppressive agents used to prevent and treat it. The results of pre-clinical studies and a phase I clinical study in patients with hematologic malignancies suggest that the costimulation blocking agent CTLA4-Ig may hold promise an agent for GVHD prophylaxis. In the present trial, the investigators are assessing the tolerability of adding abatacept to standard GVHD prophylaxis-a calcineurin inhibitor and methotrexate-in pediatric SCD patients receiving early alemtuzumab (completed by day -18) followed by fludarabine, thiotepa, and melphalan for conditioning. This trial will provide the foundation for subsequent trials designed to test the long-term hypothesis that abatacept is a safe, steroid-sparing effective adjunct to standard GVHD prophylaxis in this setting.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Standard GVHD Prophylaxis + Abatacept | Experimental | Drug: Diphenhydramine, Drug: Acetaminophen, Drug: Methylprednisolone, Drug: Meperidine, Drug: Alemtuzumab, Drug: Thymoglobulin, Drug: Fludarabine, Drug: Melphalan, Drug: Thiotepa, Drug: Cyclosporine, Drug: Tacrolimus, Drug: Methotrexate, Drug: Abatacept, Procedure: Marrow infusion, Drug: Sirolimus, Drug: Mycophenolate MofetilSubjects 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. |
Who may qualify
- Ages
- 3 to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (16 listed)
- Patients with hemoglobin (Hgb) SS or SB0 thalassemia between the ages of 3 and 20.99 years who are at least 10 kg getting an human leukocyte antigen (HLA) matched bone marrow transplant, will be eligible if they are at increased risk for graft versus host disease (GVHD) and have severe SCD.
- 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.
- Must have been evaluated and adequately counseled regarding treatment options for severe SCD by a pediatric hematologist.
- 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.
Key exclusion criteria (17 listed)
- Bridging (portal to portal) fibrosis or cirrhosis of the liver.
- 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.
- Renal dysfunction with an estimated glomerular filtration rate (GFR) < 50% of predicted normal for age.
- Cardiac dysfunction with shortening fraction < 25%.
- 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%.
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 |
|---|---|---|
| DiphenhydramineAlso: Benadryl(Standard of Care) Premedication Diphenhydramine: 1 mg/kg IV or PO q 8 hours (maximum=50 mg) | Drug | Standard GVHD Prophylaxis + Abatacept |
| AcetaminophenAlso: Tylenol(Standard of Care) Premedication Acetaminophen: 10-15 mg/kg PO q 6 hours (maximum=1000 mg) | Drug | Standard GVHD Prophylaxis + Abatacept |
| MethylprednisoloneAlso: Medrol(Standard of Care) Premedication Methylprednisolone: 0.25-0.5 mg/kg IV q 6 hours | Drug | Standard GVHD Prophylaxis + Abatacept |
| MeperidineAlso: Demerol(Standard of Care) Premedication Use as needed (PRN) Meperidine: 0.5 mg/kg IV q 4-6 hours (for rigors) | Drug | Standard GVHD Prophylaxis + Abatacept |
| AlemtuzumabAlso: Lemtrada(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. | Drug | Standard GVHD Prophylaxis + Abatacept |
| ThymoglobulinAlso: Genzyme(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. | Drug | Standard GVHD Prophylaxis + Abatacept |
| FludarabineAlso: Fludara(Standard Conditioning Regimen) Fludarabine should be administered 30 mg/m2 IV daily for five days. It should be infused over 30 to 60 minutes. | Drug | Standard GVHD Prophylaxis + Abatacept |
| MelphalanAlso: Alkeran(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. | Drug | Standard GVHD Prophylaxis + Abatacept |
| ThiotepaAlso: Thioplex(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. | Drug | Standard GVHD Prophylaxis + Abatacept |
| CyclosporineAlso: Neoral(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. | Drug | Standard GVHD Prophylaxis + Abatacept |
| TacrolimusAlso: Protopic(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. | Drug | Standard GVHD Prophylaxis + Abatacept |
| MethotrexateAlso: Trexall(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. | Drug | Standard GVHD Prophylaxis + Abatacept |
| AbataceptAlso: CTLA4-Ig, Orencia(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. | Drug | Standard GVHD Prophylaxis + Abatacept |
| Marrow infusionAlso: stem cell transplant(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 | Procedure or surgery | Standard GVHD Prophylaxis + Abatacept |
| SirolimusAlso: Rapamune(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. | Drug | Standard GVHD Prophylaxis + Abatacept |
| Mycophenolate MofetilAlso: MMF(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. | Drug | Standard GVHD Prophylaxis + Abatacept |
Primary outcome
Number of patients who tolerate abatacept
Time frame: Within 100 days of receiving the last prescribed dose of abatacept
Patients will be deemed to be evaluable for tolerability if they received all prescribed doses of abatacept. Abatacept will deemed to be tolerated, if no more than one dose is withheld per protocol stipulations, no death from an infection that occurs within 30 days of or develops post-transplant lymphoproliferative disease (PTLD) within 100 days of receiving the last prescribed dose of abatacept.
2 secondary outcomes
Bearman Scale Score of Regimen-Related Toxicity (RRT)
Time frame: Day 42 post-transplant
Number of infections
Time frame: Up to 180 days post transplant
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 13 Jun 2024.
- Individual participant dataSharing planned: No
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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.
Monica Bhatia, MD study chair
Columbia University
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Diphenhydramine, Acetaminophen and Methylprednisolone in people with Sickle Cell Disease and Graft Versus Host Disease, run by Monica Bhatia at 7 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 16 inclusion and 17 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 13 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 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 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?
Number of patients who tolerate abatacept (time frame: Within 100 days of receiving the last prescribed dose of abatacept). 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 13 Jun 2024.