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

Sheba Medical Center

Status and phase: Enrolling; Phase 2

Conditions: Graft Versus Host Disease

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

Study type: Interventional

Funder types: Other

Identifiers

NCT03357159

SHEBA-17-4055-AN-CTIL

Details and patient eligibility

About

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)

Enrollment: 30 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

30 participants in 1 patient group

cyclophosphamide and ATLG

Experimental group

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.

Treatment:

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

Drug: Cyclophosphamide