Tocilizumab for Blood Cancer Post-Transplant Care

Recruiting in Palo Alto (17 mi)

Overseen byKoen van Besien, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Weill Medical College of Cornell University

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 6 Jurisdictions

Trial Summary

What is the purpose of this trial?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).

Eligibility Criteria

Adults with certain blood cancers or disorders needing a bone marrow transplant, who can't find a matching donor quickly. They should be in relatively good health with decent organ function and no severe allergies to tocilizumab or similar drugs. Pregnant women, those with uncontrolled infections, HIV, or serious liver issues are excluded.

Inclusion Criteria

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: Serum bilirubin: <2.0 mg/dL, ALT (SGPT) <3x upper limit of normal (ULN), Creatinine Clearance: >50 mL/min/1.73m2 (eGFR as estimated by the modified MDRD equation), Left ventricular ejection fraction >40%, Pulmonary diffusion capacity >40% predicted, Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

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.

Participant Groups

The trial is testing if replacing anti-thymocyte globulin (ATG) with tocilizumab in the pre-transplant treatment regimen can improve immune recovery and reduce relapse while maintaining low graft failure and GVHD rates. It includes Fludarabine, Total Body Irradiation, Melphalan as part of the conditioning.

4Treatment groups

Experimental Treatment

Group I: ATG Group IVExperimental Treatment4 Interventions

* 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 II: ATG Group IIIExperimental Treatment5 Interventions

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 III: ATG Group IIExperimental Treatment5 Interventions

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 IV: ATG Group IExperimental Treatment5 Interventions

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.

Tocilizumab is already approved in European Union, United States, Canada, Japan, Australia for the following indications:

🇪🇺 Approved in European Union as Actemra for: