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Anti T-lymphocyte Immunoglobulin With Post Transplant Cyclophosphamide to Prevent GVHD Post Allogeneic Transplantation

Primary Purpose

Graft Versus Host Disease

Status

Recruiting

Phase

Phase 2

Locations

Israel

Study Type

Interventional

Intervention

Cyclophosphamide

anti-human T-lymphocyte immunoglobulin (ATLG)

About this trial

This is an interventional treatment trial for Graft Versus Host Disease focused on measuring anti thymocyte globulin, cyclophospamide, graft-versus-host disease, stem cell transplantation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients with MDS/AML
18 years or older and willing and able to comply with the protocol requirements.
LVEF ≥ 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available.
Patients undergoing 8-10/10 HLA matched unrelated and unmanipulated PBSC transplantation
Patients conditioned with reduced intensity or reduced toxicity conditioning of fludarabine with reduced dose (2 days) or myeloabalative doses (4 days) of busulfan or with treosulfan.
Patients must sign written informed consent.
Adequate birth control in fertile patients.

Exclusion Criteria:

Patients undergoing other type of transplantation or with other type of basic disease other than AML or MDS.
Patients with respiratory failure (DLCO < 30%).
Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention.
Psychiatric conditions/disease that impair the ability to give informed consent or to adequately co-operate
Bilirubin > 3.0 mg/dl, transaminases > 3 times upper normal limit
Creatinine > 2.0 mg/dl
ECOG-Performance status > 2
Uncontrolled infection
Pregnancy or lactation
CNS disease involvement
Pleural effusion or ascites > 1 liter.

Sites / Locations

Chaim Sheba Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

cyclophosphamide and ATLG

Arm Description

The study will include 2 phases. In the first phase escalated doses of post-transplant cyclophosphamide up to a maximal dose of 50 mg/kg administered on day +3 and +4 (target dose) will be added to a standard GVHD prophylaxis consisting of anti-human T-lymphocyte immunoglobulin (ATLG, Grafalon®, formerly ATG-Fresenius S, Neovii Pharmaceuticals) 15mg/kg total (5mg/kg day) on days -3 to -1 pre transplantation in order to find the maximally tolerated dose (MTD) of post-transplant cyclophosphamide (PTCy) in combination with pre-transplant immunosuppression by ATLG. The second phase will use the MTD cyclophosphamide dose identified in the first phase.

Outcomes

Primary Outcome Measures

Overal survival

Overall survival will be calculated from the day of SCT until death or last follow-up. OS will be determined using Kaplan-Meyer product limit method.

Disease-free survival

Disease-free survival will be calculated from the day of SCT until relapse, death of any cause, or last follow-up. DFS will be determined using Kaplan-Meyer product limit method.

Secondary Outcome Measures

Full Information

NCT ID

NCT03357159

First Posted

October 9, 2017

Last Updated

May 4, 2022

Sponsor

Sheba Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT03357159

Brief Title

Anti T-lymphocyte Immunoglobulin With Post Transplant Cyclophosphamide to Prevent GVHD Post Allogeneic Transplantation

Official Title

A Phase II Study of Neovii Anti-human T-lymphocyte Immunoglobulin (ATLG, Grafalon®) With Post Transplant Escalated Doses of Post-transplant-Cyclophosphamide to Prevent Acute and Chronic GVHD Post Allogeneic Stem Cell Transplantation

Study Type

Interventional

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Recruiting

Study Start Date

September 6, 2018 (Actual)

Primary Completion Date

December 1, 2022 (Anticipated)

Study Completion Date

December 1, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Sheba Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

Investigators hypothesize that combination of ATLG with PTCy in matched or mismatched unrelated hematopoietic stem cell transplantation will reduce acute and chronic GVHD incidence. Furthermore it will allow shortening of the length of post-transplantation immunosuppression with calcineurin inhibitor (CNI) administration (currently administrated in addition to ATG as GVHD prophylaxis in daily common practice)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Graft Versus Host Disease

Keywords

anti thymocyte globulin, cyclophospamide, graft-versus-host disease, stem cell transplantation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

The patients will get conventional GVHD prophylaxis consisting of ATLG 15mg/kg total (5mg/kg day) on days -3 to -1 pre transplantation. Cyclophosphamide at 25mg/kg dose will be administrated at day +3 post infusion of the stem cell (SC) graft to the first 3 patients. If no > grade II toxicity* occurs, the next 3 patients will receive cyclophosphamide at 25mg/kg dose at day +3 and +4 post SC graft infusion. If no > grade II toxicity*occurs, the next 3 patients will receive cyclophosphamide at 37.5 mg/kg dose at day +3 and +4 post SC graft infusion. If no > grade II toxicity* occurs, the next 3 patients will receive the target dose of cyclophosphamide at 50 mg/kg dose on day +3 and +4 post SC graft infusion. The residual 18 patients will receive cyclophosphamide at the maximal tolerated dose (MTD) established in the first part of the study. Patients will also receive GVHD prophylaxis consisting of a cyclosporine and cellcept starting on day +5 after transplantation.

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

cyclophosphamide and ATLG

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Intervention Description

In the first phase escalated doses of post-transplant cyclophosphamide up to a maximal dose of 50 mg/kg , the second phase will use the MTD cyclophosphamide dose identified in the first phase.

Intervention Type

Drug

Intervention Name(s)

anti-human T-lymphocyte immunoglobulin (ATLG)

Intervention Description

15mg/kg total (5mg/kg day) on days -3 to -1 pre transplantation

Primary Outcome Measure Information:

Title

Overal survival

Description

Overall survival will be calculated from the day of SCT until death or last follow-up. OS will be determined using Kaplan-Meyer product limit method.

Time Frame

24 months

Title

Disease-free survival

Description

Disease-free survival will be calculated from the day of SCT until relapse, death of any cause, or last follow-up. DFS will be determined using Kaplan-Meyer product limit method.

Time Frame

24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients with MDS/AML 18 years or older and willing and able to comply with the protocol requirements. LVEF ≥ 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available. Patients undergoing 8-10/10 HLA matched unrelated and unmanipulated PBSC transplantation Patients conditioned with reduced intensity or reduced toxicity conditioning of fludarabine with reduced dose (2 days) or myeloabalative doses (4 days) of busulfan or with treosulfan. Patients must sign written informed consent. Adequate birth control in fertile patients. Exclusion Criteria: Patients undergoing other type of transplantation or with other type of basic disease other than AML or MDS. Patients with respiratory failure (DLCO < 30%). Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention. Psychiatric conditions/disease that impair the ability to give informed consent or to adequately co-operate Bilirubin > 3.0 mg/dl, transaminases > 3 times upper normal limit Creatinine > 2.0 mg/dl ECOG-Performance status > 2 Uncontrolled infection Pregnancy or lactation CNS disease involvement Pleural effusion or ascites > 1 liter.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Arnon Nagler, MD

Phone

972-3-530-58-30

Arnon.Nagler@sheba.health.gov.il

First Name & Middle Initial & Last Name or Official Title & Degree

Avichai Shimoni, MD

ashimoni@sheba.health.gov.il

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Arnon Nagler, MD

Organizational Affiliation

Sheba Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Chaim Sheba Medical Center

City

Ramat Gan

ZIP/Postal Code

57261

Country

Israel

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Arnon Nagler, M.D.

First Name & Middle Initial & Last Name & Degree

M.D.

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Anti T-lymphocyte Immunoglobulin With Post Transplant Cyclophosphamide to Prevent GVHD Post Allogeneic Transplantation

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