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

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ClinicalTrials.gov Identifier: NCT03357159
Recruitment Status : Recruiting
First Posted : November 29, 2017
Last Update Posted : September 19, 2019
Sponsor:
Information provided by (Responsible Party):
Prof Arnon Nagler, Sheba Medical Center

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)

Condition or disease Intervention/treatment Phase
Graft Versus Host Disease Drug: Cyclophosphamide Drug: anti-human T-lymphocyte immunoglobulin (ATLG) Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Intervention 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)
Primary Purpose: Treatment
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
Actual Study Start Date : September 6, 2018
Estimated Primary Completion Date : December 1, 2019
Estimated Study Completion Date : December 1, 2020


Arm Intervention/treatment
Experimental: 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.
Drug: 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.

Drug: anti-human T-lymphocyte immunoglobulin (ATLG)
15mg/kg total (5mg/kg day) on days -3 to -1 pre transplantation




Primary Outcome Measures :
  1. Overal survival [ Time Frame: 24 months ]
    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.

  2. Disease-free survival [ Time Frame: 24 months ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03357159


Contacts
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Contact: Arnon Nagler, MD 972-3-530-58-30 Arnon.Nagler@sheba.health.gov.il
Contact: Avichai Shimoni, MD ashimoni@sheba.health.gov.il

Locations
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Israel
Chaim Sheba Medical Center Recruiting
Ramat Gan, Israel, 57261
Contact: Arnon Nagler, M.D.         
Contact: , M.D.         
Sponsors and Collaborators
Sheba Medical Center
Investigators
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Principal Investigator: Arnon Nagler, MD Sheba Medical Center

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Responsible Party: 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, Sheba Medical Center
ClinicalTrials.gov Identifier: NCT03357159     History of Changes
Other Study ID Numbers: SHEBA-17-4055-AN-CTIL
First Posted: November 29, 2017    Key Record Dates
Last Update Posted: September 19, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Prof Arnon Nagler, Sheba Medical Center:
anti thymocyte globulin
cyclophospamide
graft-versus-host disease
stem cell transplantation
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases
Cyclophosphamide
Antilymphocyte Serum
Immunoglobulins
Antibodies
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists