Tocilizumab for the Prevention of Graft Failure and GVHD in Haplo-Cord Transplantation

NCT ID: NCT04395222

Last Updated: 2026-01-06

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-07
• Study Completion Date: 2027-06-30

Brief Summary

The purpose of this study is to evaluate the safety of reducing and ultimately eliminating anti-thymocyte globulin (ATG) from the haplo-cord transplant conditioning regimen and replacing it with tocilizumab, an IL-6 receptor monoclonal antibody, to improve immune reconstitution and reduce relapse while preserving low rates of graft failure and graft versus host disease (GVHD).

Detailed Description

This study is a prospective phase II non-inferiority study investigating tocilizumab as a potential alternative to anti-thymocyte globulin (ATG) in haplo-cord transplantation. It is a single-center study based at Weill Cornell Medicine/NewYork Presbyterian Hospital.

The hypothesis is that tocilizumab is a safe and effective alternative to ATG in haplo-cord transplantation, facilitating transient engraftment of the haplo-identical stem cell graft without prolonged neutropenia or second nadir prior to durable cord engraftment while also preventing graft versus host disease (GVHD).

This study plans to enroll patients with hematologic malignancies in need of alternate donor transplant. All subjects will be conditioned with fludarabine, melphalan and total body irradiation (TBI), followed by a single dose of tocilizumab 8 mg/kg on Day -1. Patients will be enrolled into 4 successive cohorts, initially administering the current standard 3 doses of ATG 1.5 mg/kg (total 4.5 mg/kg). In the absence of safety signals, we will drop one dose of ATG in successive cohorts until the drug ultimately has been eliminated.

The primary endpoint of the study is successful haplo-derived neutrophil engraftment. Treatment will only be of interest if there is evidence that this rate is greater than 60%. If there are 4 or fewer successes, that dose group will be deemed unacceptable and the next higher ATG dose for which there were 5 or more success will be expanded.

Conditions

Hematologic Malignancy; Bone Marrow Transplant

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ATG Group I

Anti-thymocyte Globulin (ATG) 1.5 mg/kg administered on Day -5, Day -3 and Day -1 of the transplant conditioning regimen.

• Fludarabine 30mg/m2 administered on Day -7 through Day -3 of transplant conditioning regimen (if under 60 years old), or on Day -5 through Day -3 of transplant conditioning regimen (if over 60 years old)
• Melphalan 140 mg/m2 administered on Day -2 of transplant conditioning regimen.
• Total Body Irradiation 2 Gray administered on Day -4, Day -3 of transplant conditioning regimen.
• Tocilizumab 8 mg/kg administered on Day -1 of transplant conditioning regimen.

Group Type: EXPERIMENTAL

Tocilizumab

Intervention Type: DRUG

Tocilizumab 8 mg/kg intravenously administered as a single dose on Day -1 of transplant conditioning regimen

Fludarabine

Intervention Type: DRUG

Fludarabine 30 mg/m2 intravenously administered on Day -7, Day -6, Day -5, Day -4, Day -3 of transplant conditioning regimen if under the age of 60. If over the age of 60, Fludarabine 30 mg/m2 intravenously administered on Day -5, Day -4 and Day -3 of transplant conditioning regimen.

Melphalan

Intervention Type: DRUG

Melphalan 140 mg/m2 intravenously administered on Day -2 of transplant conditioning regimen.

Anti-thymocyte globulin (rabbit)

Intervention Type: DRUG

Anti-thymocyte globulin (ATG) 1.5 mg/kg

Total Body Irradiation

Intervention Type: RADIATION

Total Body Irradiation (TBI) 2 Gray, administered on Day -4 and Day -3 of transplant conditioning regimen

ATG Group II

Anti-thymocyte Globulin (ATG) 1.5 mg/kg administered on Day -5, and Day -3 of the transplant conditioning regimen.

• Fludarabine 30mg/m2 administered on Day -7 through Day -3 of transplant conditioning regimen (if under 60 years old), or on Day -5 through Day -3 of transplant conditioning regimen (if over 60 years old)
• Melphalan 140 mg/m2 administered on Day -2 of transplant conditioning regimen.
• Total Body Irradiation 2 Gray administered on Day -4, Day -3 of transplant conditioning regimen.
• Tocilizumab 8 mg/kg administered on Day -1 of transplant conditioning regimen.

Group Type: EXPERIMENTAL

Tocilizumab

Intervention Type: DRUG

Tocilizumab 8 mg/kg intravenously administered as a single dose on Day -1 of transplant conditioning regimen

Fludarabine

Intervention Type: DRUG

Fludarabine 30 mg/m2 intravenously administered on Day -7, Day -6, Day -5, Day -4, Day -3 of transplant conditioning regimen if under the age of 60. If over the age of 60, Fludarabine 30 mg/m2 intravenously administered on Day -5, Day -4 and Day -3 of transplant conditioning regimen.

Melphalan

Intervention Type: DRUG

Melphalan 140 mg/m2 intravenously administered on Day -2 of transplant conditioning regimen.

Anti-thymocyte globulin (rabbit)

Intervention Type: DRUG

Anti-thymocyte globulin (ATG) 1.5 mg/kg

Total Body Irradiation

Intervention Type: RADIATION

Total Body Irradiation (TBI) 2 Gray, administered on Day -4 and Day -3 of transplant conditioning regimen

ATG Group III

Anti-thymocyte Globulin (ATG) 1.5 mg/kg administered on Day -5 of the transplant conditioning regimen.

• Fludarabine 30mg/m2 administered on Day -7 through Day -3 of transplant conditioning regimen (if under 60 years old), or on Day -5 through Day -3 of transplant conditioning regimen (if over 60 years old)
• Melphalan 140 mg/m2 administered on Day -2 of transplant conditioning regimen.
• Total Body Irradiation 2 Gray administered on Day -4, Day -3 of transplant conditioning regimen.
• Tocilizumab 8 mg/kg administered on Day -1 of transplant conditioning regimen.

Group Type: EXPERIMENTAL

Tocilizumab

Intervention Type: DRUG

Tocilizumab 8 mg/kg intravenously administered as a single dose on Day -1 of transplant conditioning regimen

Fludarabine

Intervention Type: DRUG

Fludarabine 30 mg/m2 intravenously administered on Day -7, Day -6, Day -5, Day -4, Day -3 of transplant conditioning regimen if under the age of 60. If over the age of 60, Fludarabine 30 mg/m2 intravenously administered on Day -5, Day -4 and Day -3 of transplant conditioning regimen.

Melphalan

Intervention Type: DRUG

Melphalan 140 mg/m2 intravenously administered on Day -2 of transplant conditioning regimen.

Anti-thymocyte globulin (rabbit)

Intervention Type: DRUG

Anti-thymocyte globulin (ATG) 1.5 mg/kg

Total Body Irradiation

Intervention Type: RADIATION

Total Body Irradiation (TBI) 2 Gray, administered on Day -4 and Day -3 of transplant conditioning regimen

ATG Group IV

• Fludarabine 30mg/m2 administered on Day -7 through Day -3 of transplant conditioning regimen (if under 60 years old), or on Day -5 through Day -3 of transplant conditioning regimen (if over 60 years old)
• Melphalan 140 mg/m2 administered on Day -2 of transplant conditioning regimen.
• Total Body Irradiation 2 Gray administered on Day -4, Day -3 of transplant conditioning regimen.
• Tocilizumab 8 mg/kg administered on Day -1 of transplant conditioning regimen.

Group Type: EXPERIMENTAL

Tocilizumab

Intervention Type: DRUG

Tocilizumab 8 mg/kg intravenously administered as a single dose on Day -1 of transplant conditioning regimen

Fludarabine

Intervention Type: DRUG

Fludarabine 30 mg/m2 intravenously administered on Day -7, Day -6, Day -5, Day -4, Day -3 of transplant conditioning regimen if under the age of 60. If over the age of 60, Fludarabine 30 mg/m2 intravenously administered on Day -5, Day -4 and Day -3 of transplant conditioning regimen.

Melphalan

Intervention Type: DRUG

Melphalan 140 mg/m2 intravenously administered on Day -2 of transplant conditioning regimen.

Total Body Irradiation

Intervention Type: RADIATION

Total Body Irradiation (TBI) 2 Gray, administered on Day -4 and Day -3 of transplant conditioning regimen

Interventions

Tocilizumab

Tocilizumab 8 mg/kg intravenously administered as a single dose on Day -1 of transplant conditioning regimen

Intervention Type: DRUG

Fludarabine

Fludarabine 30 mg/m2 intravenously administered on Day -7, Day -6, Day -5, Day -4, Day -3 of transplant conditioning regimen if under the age of 60. If over the age of 60, Fludarabine 30 mg/m2 intravenously administered on Day -5, Day -4 and Day -3 of transplant conditioning regimen.

Intervention Type: DRUG

Melphalan

Melphalan 140 mg/m2 intravenously administered on Day -2 of transplant conditioning regimen.

Intervention Type: DRUG

Anti-thymocyte globulin (rabbit)

Anti-thymocyte globulin (ATG) 1.5 mg/kg

Intervention Type: DRUG

Total Body Irradiation

Total Body Irradiation (TBI) 2 Gray, administered on Day -4 and Day -3 of transplant conditioning regimen

Intervention Type: RADIATION

Other Intervention Names

Actemra; Fludara; Alkeran; Thymoglobulin

Eligibility Criteria

Inclusion Criteria

1. Subject must have a confirmed diagnosis of one of the following:

1. Relapsed or refractory acute leukemia (myeloid or lymphoid)

2. Acute leukemia in first remission at high-risk for recurrence

3. Chronic myelogenous leukemia in chronic, accelerated phase or blast-crisis

4. Myelodysplastic syndromes

5. Chronic myeloproliferative disease

6. Recurrent, refractory or high-risk malignant lymphoma

7. Chronic lymphocytic leukemia, relapsed or with poor prognostic features

8. Multiple myeloma

9. Other hematological disorder in need of allogeneic transplant (e.g. blastoid dendritic cell neoplasm)

2. Age ≥ 18 years.

3. Likely to benefit from allogeneic transplant in the opinion of the transplant physician.

4. An HLA-identical related or unrelated donor cannot be identified within an appropriate time frame.

5. Karnofsky Performance Status (KPS) of ≥ 70%.

6. Acceptable organ function as defined below:

1. Serum bilirubin: <2.0 mg/dL

2. ALT (SGPT) <3x upper limit of normal (ULN)

3. Creatinine Clearance: >50 mL/min/1.73m2 (eGFR as estimated by the modified MDRD equation)

4. Left ventricular ejection fraction >40%

5. Pulmonary diffusion capacity >40% predicted

7. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

1. Life expectancy is severely limited by concomitant illness or uncontrolled infection.

2. Evidence of chronic active hepatitis or cirrhosis

3. Uncontrolled HIV disease.

4. Pregnancy or lactation.

5. History of complicated diverticulitis, including fistulae, abscess formation or gastrointestinal perforation

6. History of allergic reactions attributed to compounds of similar chemical or biological composition as tocilizumab, including known allergies to Chinese hamster ovary cell products or other recombinant human or humanized antibodies.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alexandra Gomez Arteaga, MD

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

Weill Cornell Medical College

New York, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

19-08020738

Identifier Type: -

Identifier Source: org_study_id