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

NCT ID: NCT03357159

Last Updated: 2023-11-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-09-06

Study Completion Date

2024-12-01

Brief Summary

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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)

Detailed Description

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Conditions

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Graft Versus Host Disease

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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cyclophosphamide and ATLG

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.

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

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.

anti-human T-lymphocyte immunoglobulin (ATLG)

Intervention Type DRUG

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

Interventions

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Cyclophosphamide

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

anti-human T-lymphocyte immunoglobulin (ATLG)

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Patients with MDS/AML
2. 18 years or older and willing and able to comply with the protocol requirements.
3. LVEF ≥ 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available.
4. Patients undergoing 8-10/10 HLA matched unrelated and unmanipulated PBSC transplantation
5. 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.
6. Patients must sign written informed consent.
7. Adequate birth control in fertile patients.

Exclusion Criteria

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

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sheba Medical Center

OTHER_GOV

Sponsor Role lead

Responsible Party

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Prof Arnon Nagler

M.D., M.Sc, Professor of Medicine Tel Aviv University, Director Hematology Division, Chair Israeli BMT Association,Chair of the ALWP of the EBMT, Co-Chair Scientific Council of the EBMT Chaim Sheba Medical Center

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Arnon Nagler, MD

Role: PRINCIPAL_INVESTIGATOR

Sheba Medical Center

Locations

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Chaim Sheba Medical Center

Ramat Gan, , Israel

Site Status RECRUITING

Countries

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Israel

Central Contacts

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Arnon Nagler, MD

Role: CONTACT

972-3-530-58-30

Avichai Shimoni, MD

Role: CONTACT

Facility Contacts

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Arnon Nagler, M.D.

Role: primary

M.D.

Role: backup

Other Identifiers

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SHEBA-17-4055-AN-CTIL

Identifier Type: -

Identifier Source: org_study_id