Abatacept for GVHD Prophylaxis After Hematopoietic Stem Cell Transplantation for Pediatric Sickle Cell Disease

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 conditioning.

Conditions

• Sickle Cell Disease
• Graft Versus Host Disease

Interventions

DRUG

Diphenhydramine

(Standard of Care) Premedication Diphenhydramine: 1 mg/kg IV or PO q 8 hours (maximum=50 mg)

DRUG

Acetaminophen

(Standard of Care) Premedication Acetaminophen: 10-15 mg/kg PO q 6 hours (maximum=1000 mg)

DRUG

Methylprednisolone

(Standard of Care) Premedication Methylprednisolone: 0.25-0.5 mg/kg IV q 6 hours

DRUG

Meperidine

(Standard of Care) Premedication Use as needed (PRN) Meperidine: 0.5 mg/kg IV q 4-6 hours (for rigors)

DRUG

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.

DRUG

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.

DRUG

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.

DRUG

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.

DRUG

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.

DRUG

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.

DRUG

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.

DRUG

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.

DRUG

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.

PROCEDURE

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

DRUG

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.

DRUG

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.

Sponsors & Collaborators

• Monica Bhatia

  lead OTHER

Principal Investigators

• Monica Bhatia, MD · Columbia University

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

3 Years

Max Age

20 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-07-31

Primary Completion

2021-12-30

Completion

2023-12-30

FDA Drug

Yes

Countries

• United States

Study Locations