In-vivo Regulatory T Cell Enhancement With Cyclophosphamide and Sirolimus (T-REG)

Hackensack Meridian Health

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Graft Versus Host Disease

Treatments: Drug: Low dose IL-2 with Cytoxan + Sirolimus; Drug: Low dose IL-2, low dose Vidaza, cyclophosphamide & Sirolimus; Drug: Cyclophosphamide and Sirolimus; Drug: Low dose IL-2, Vidaza, Cytoxan & Sirolimus

Study type: Interventional

Funder types: Other

Identifiers

NCT01453140

TREG - Pro2219

Details and patient eligibility

About

In this study the investigators are proposing to treat patients with steroid-refractory Graft-versus-host Disease (GVHD) stabilization using IL-2 and azacitidine

Full description

High-dose cyclophosphamide and sirolimus have been successfully used for the prevention of Graft-versus-host Disease (GVHD) and have shown to enhance the Tregs subpopulation. The addition of low dose IL-2 and a demethylating agent such as azacitidine will also be studied in an attempt to promote and stabilize the FoxP3 expression of Tregs.

Enrollment: 3 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients must have a documented clinical diagnosis of grade II-IV acute graft-versus- host disease defined as graft versus host disease (GVHD) occurring within the first 100 days of transplantation
• Patients must be steroid-refractory defines as progression after 3 days of corticosteroid therapy or no response after 5 days of corticosteroid therapy.
• Progression is defined as up-grading
• No response is defined as no down-grading
• Progression after 3 days requires patients to have received at least 2 mg/mg/day for a total of 6 mg/kg of methylprednisolone or its equivalent.
• No response after 5 days requires patient to have received at least 2 mg/kg/d for a total of 10 mg/kg of methylprednisolone or its equivalent.
• Patients with exacerbation of GVHD during steroid taper will require re-treatment with 2mg/kg/d of corticosteroids and will need to meet the criteria
• Age 18-70
• Patients must have received an allogeneic hematopoietic stem cell transplant within 100 days of study enrollment.
• Serum creatinine < 2 mg/dL

Exclusion criteria

• Patients cannot have active central nervous system (CNS) disease.
• Patients must not have received cyclophosphamide for GVHD prophylaxis
• Patients must not have pneumonia requiring oxygen supplementation
• Unable or unwilling to sign informed consent.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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3 participants in 3 patient groups

Cyclophosphamide and Sirolimus

Experimental group

Description:

cyclophosphamide and sirolimus combo

Treatment:

Drug: Cyclophosphamide and Sirolimus

Drug: Cyclophosphamide and Sirolimus

Lowdose IL-2, Cytoxan + Sirolimus

Experimental group

Description:

Low dose IL-2 with Cytoxan + Sirolimus Patients in treatment arm B will be receiving low-dose IL-2 in conjunction with the cyclophosphamide and sirolimus.

Treatment:

Drug: Low dose IL-2 with Cytoxan + Sirolimus

Drug: Low dose IL-2 with Cytoxan + Sirolimus

Lowdose IL-2, Vidaza, cyclophosphamide & Sirolimus

Experimental group

Description:

Lowdose IL-2, Vidaza, cyclophosphamide (Cytoxan) \& Sirolimus Patients in treatment arm C will be receiving low-dose azacitidine (Vidaza).

Treatment:

Drug: Low dose IL-2, Vidaza, Cytoxan & Sirolimus

Drug: Low dose IL-2, low dose Vidaza, cyclophosphamide & Sirolimus