In-vivo Regulatory T Cell Enhancement With Cyclophosphamide and Sirolimus

NCT ID: NCT01453140

Last Updated: 2022-03-02

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

3 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-08-31

Study Completion Date

2012-07-31

Brief Summary

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

Detailed Description

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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.

Conditions

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Graft Versus Host Disease

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cyclophosphamide and Sirolimus

cyclophosphamide and sirolimus combo

Group Type EXPERIMENTAL

Cyclophosphamide and Sirolimus

Intervention Type DRUG

On the first day of treatment, cyclophosphamide will be administered at a dose of 4g/m2 IV x 1 dose. Patients who are \>40% above ideal weight will be dosed based on adjusted weight and adjusted BSA.

One day after the administration of cyclophosphamide, patients will receive sirolimus 6 mg PO x 1 and on the following day will start sirolimus at a dose of 2 mg PO daily.

Cyclophosphamide and Sirolimus

Intervention Type DRUG

Day 1: Cyclophosphamide Day 2: Sirolimus

Lowdose IL-2, Cytoxan + Sirolimus

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.

Group Type EXPERIMENTAL

Low dose IL-2 with Cytoxan + Sirolimus

Intervention Type DRUG

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

IL-2 will be administered at a dose of 0.5E6 IU/m2 SQ daily x 8 weeks followed by 4 weeks off, starting 14 days after the cyclophosphamide.

Low dose IL-2 with Cytoxan + Sirolimus

Intervention Type DRUG

treatment arm B will be receiving low-dose IL-2 in conjunction with the cyclophosphamide and sirolimus

Lowdose IL-2, Vidaza, cyclophosphamide & Sirolimus

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

Group Type EXPERIMENTAL

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

Intervention Type DRUG

Patients in treatment arm C will be receiving low-dose azacitidine (Vidaza). The Vidaza will be initiated between day 27 and 32 following the cyclophosphamide.

The dose administered will be 10 mg SQ daily for 5 days followed by 3 weeks off.

Low dose IL-2, Vidaza, Cytoxan & Sirolimus

Intervention Type DRUG

Vidaza will be initiated between day 27 and 32 following the cyclophosphamide.

Interventions

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Cyclophosphamide and Sirolimus

On the first day of treatment, cyclophosphamide will be administered at a dose of 4g/m2 IV x 1 dose. Patients who are \>40% above ideal weight will be dosed based on adjusted weight and adjusted BSA.

One day after the administration of cyclophosphamide, patients will receive sirolimus 6 mg PO x 1 and on the following day will start sirolimus at a dose of 2 mg PO daily.

Intervention Type DRUG

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.

IL-2 will be administered at a dose of 0.5E6 IU/m2 SQ daily x 8 weeks followed by 4 weeks off, starting 14 days after the cyclophosphamide.

Intervention Type DRUG

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

Patients in treatment arm C will be receiving low-dose azacitidine (Vidaza). The Vidaza will be initiated between day 27 and 32 following the cyclophosphamide.

The dose administered will be 10 mg SQ daily for 5 days followed by 3 weeks off.

Intervention Type DRUG

Cyclophosphamide and Sirolimus

Day 1: Cyclophosphamide Day 2: Sirolimus

Intervention Type DRUG

Low dose IL-2 with Cytoxan + Sirolimus

treatment arm B will be receiving low-dose IL-2 in conjunction with the cyclophosphamide and sirolimus

Intervention Type DRUG

Low dose IL-2, Vidaza, Cytoxan & Sirolimus

Vidaza will be initiated between day 27 and 32 following the cyclophosphamide.

Intervention Type DRUG

Other Intervention Names

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Cytoxan Interleukin-2 Cytoxan Interleukin-2 Azactidine Cytoxan Other names: Cytoxan Other names: Interleukin-2 Cytoxan Other names: Interleukin-2 Azactidine Cytoxan

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hackensack Meridian Health

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michele Donato, MD

Role: PRINCIPAL_INVESTIGATOR

Hackensack Meridian Health

Locations

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John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Countries

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United States

Other Identifiers

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TREG - Pro2219

Identifier Type: -

Identifier Source: org_study_id

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