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

NCT04395222 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 19-08020738
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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).

Conditions

Bone Marrow Transplant; Hematologic Malignancy

Keywords

Tocilizumab; Haplo-Cord Transplant; Allogeneic Transplant; Hematologic Malignancies

Outcome Measures

Primary Outcomes (1)

• Percentage of Subjects With Successful Haplo-derived Neutrophil Engraftment

  This is defined as: 1. Achieve an absolute neutrophil count (ANC) of 500 cells/microL for three consecutive days with the first on or prior to Day +21 post-transplant, AND 2. Absence of a second nadir - a drop in the ANC to \<300 cells/microL for five consecutive days - after initial neutrophil recovery.

  21 days post-transplant

Secondary Outcomes (7)

• Progression-Free Survival

  5 years post-transplant

• Overall Survival

  5 years post-transplant

• Transplant-Related Mortality

  5 years post-transplant

• Proportion of Platelet Engraftment Success

  6 months post-transplant

• Proportion of Failure of the Haplo-Graft

  21 days post-transplant

Study Arms (4)

ATG Group I

EXPERIMENTAL

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.

Drug: Tocilizumab; Drug: Fludarabine; Drug: Melphalan; Drug: Anti-thymocyte globulin (rabbit); Radiation: Total Body Irradiation

ATG Group II

EXPERIMENTAL

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.

Drug: Tocilizumab; Drug: Fludarabine; Drug: Melphalan; Drug: Anti-thymocyte globulin (rabbit); Radiation: Total Body Irradiation

ATG Group III

EXPERIMENTAL

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.

Drug: Tocilizumab; Drug: Fludarabine; Drug: Melphalan; Drug: Anti-thymocyte globulin (rabbit); Radiation: Total Body Irradiation

ATG Group IV

EXPERIMENTAL

* 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.

Drug: Tocilizumab; Drug: Fludarabine; Drug: Melphalan; Radiation: Total Body Irradiation

Interventions

Tocilizumab DRUG

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

Also known as: Actemra

ATG Group I; ATG Group II; ATG Group III; ATG Group IV

Fludarabine 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.

Also known as: Fludara

ATG Group I; ATG Group II; ATG Group III; ATG Group IV

Melphalan DRUG

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

Also known as: Alkeran

ATG Group I; ATG Group II; ATG Group III; ATG Group IV

Total Body Irradiation RADIATION

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

ATG Group I; ATG Group II; ATG Group III; ATG Group IV

Anti-thymocyte globulin (rabbit) DRUG

Anti-thymocyte globulin (ATG) 1.5 mg/kg

Also known as: Thymoglobulin

ATG Group I; ATG Group II; ATG Group III

Eligibility Criteria

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

You may qualify if:

• Subject must have a confirmed diagnosis of one of the following:
• Relapsed or refractory acute leukemia (myeloid or lymphoid)
• Acute leukemia in first remission at high-risk for recurrence
• Chronic myelogenous leukemia in chronic, accelerated phase or blast-crisis
• Myelodysplastic syndromes
• Chronic myeloproliferative disease
• Recurrent, refractory or high-risk malignant lymphoma
• Chronic lymphocytic leukemia, relapsed or with poor prognostic features
• Multiple myeloma
• Other hematological disorder in need of allogeneic transplant (e.g. blastoid dendritic cell neoplasm)
• Age ≥ 18 years.
• Likely to benefit from allogeneic transplant in the opinion of the transplant physician.
• An HLA-identical related or unrelated donor cannot be identified within an appropriate time frame.
• Karnofsky Performance Status (KPS) of ≥ 70%.
• Acceptable organ function as defined below:

You may not qualify if:

• Life expectancy is severely limited by concomitant illness or uncontrolled infection.
• Evidence of chronic active hepatitis or cirrhosis
• Uncontrolled HIV disease.
• Pregnancy or lactation.
• History of complicated diverticulitis, including fistulae, abscess formation or gastrointestinal perforation
• 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.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

tocilizumab; fludarabine; fludarabine phosphate; Melphalan; Antilymphocyte Serum; thymoglobulin; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Radiotherapy; Therapeutics; Investigative Techniques

Results Point of Contact

• Title: Alexandra Gomez Arteaga, MD
• Organization: Weill Cornell Medicine

alg9117@med.cornell.edu

646-962-7950

Study Officials

• Alexandra Gomez Arteaga, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2020
• First Posted: May 20, 2020
• Study Start: October 7, 2020
• Primary Completion: September 28, 2022
• Study Completion (Estimated): June 1, 2027
• Last Updated: January 6, 2026
• Results First Posted: October 23, 2023

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)