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

NCT03357159 | Unknown Phase 2

• 1 other identifier: SHEBA-17-4055-AN-CTIL
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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)

Conditions

Graft Versus Host Disease

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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.

  24 months

• 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.

  24 months

Study Arms (1)

cyclophosphamide and ATLG

EXPERIMENTAL

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.

Drug: Cyclophosphamide; Drug: anti-human T-lymphocyte immunoglobulin (ATLG)

Interventions

Cyclophosphamide 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.

cyclophosphamide and ATLG

anti-human T-lymphocyte immunoglobulin (ATLG) DRUG

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

cyclophosphamide and ATLG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with MDS/AML
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sheba Medical Center: lead

Study Sites (1)

Chaim Sheba Medical Center

Ramat Gan, 57261, Israel

RECRUITING

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Arnon Nagler, MD

  Sheba Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Arnon Nagler, MD

CONTACT

972-3-530-58-30; Arnon.Nagler@sheba.health.gov.il

Avichai Shimoni, MD

CONTACT

ashimoni@sheba.health.gov.il

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: 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

Model Details: 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.

Study Record Dates

• First Submitted: October 9, 2017
• First Posted: November 29, 2017
• Study Start: September 6, 2018
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: November 28, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)