Tocilizumab for Blood Cancer Post-Transplant Care

Overseen By Meredith Mullane, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Weill Medical College of Cornell University

Disqualifiers: Uncontrolled infection, Hepatitis, HIV, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

21 Participants Needed

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).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Tocilizumab for blood cancer post-transplant care?

Tocilizumab has been shown to be effective in treating rheumatoid arthritis, a condition involving inflammation, by blocking a protein called interleukin-6 (IL-6) that contributes to inflammation. This suggests it might help manage inflammation-related issues in other conditions, like post-transplant care for blood cancer. ^{1 2 3 4 5}

Is tocilizumab safe for humans?

Tocilizumab, also known as Actemra or RoActemra, has been generally well tolerated in clinical trials for conditions like juvenile idiopathic arthritis and rheumatoid arthritis. Common side effects include infections like upper respiratory tract infections, and some patients may experience serious infections or changes in blood tests, such as low white blood cell counts and elevated liver enzymes. ^{2 6 7 8 9}

How is the drug Tocilizumab unique for blood cancer post-transplant care?

Tocilizumab is unique because it targets and blocks the interleukin-6 receptor, which plays a role in inflammation, making it different from other treatments that focus on directly attacking cancer cells. This mechanism can help manage complications like graft-versus-host disease after a transplant, which is not directly addressed by standard cancer therapies. ^{10 11 12 13 14}

Research Team

Alexandra Gomez Arteaga, MD

Principal Investigator

Weill Medical College of Cornell University

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.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning and Transplantation

Participants undergo conditioning with fludarabine, melphalan, total body irradiation, and receive tocilizumab and potentially anti-thymocyte globulin (ATG) as part of the transplant regimen

7 days

Daily visits for conditioning regimen

Post-Transplant Monitoring

Participants are monitored for successful neutrophil engraftment and absence of second nadir

3 weeks

Frequent visits for monitoring engraftment

Follow-up

Participants are monitored for progression-free survival, overall survival, and graft-versus-host disease

5 years

Treatment Details

Interventions

• Tocilizumab

Trial Overview 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.

Participant Groups

Group I: ATG Group IV Experimental Treatment 4 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 III Experimental Treatment 5 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 II Experimental Treatment 5 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 I Experimental Treatment 5 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 for the following indications:

Approved in European Union as Actemra for:

• Rheumatoid Arthritis
• Systemic Juvenile Idiopathic Arthritis
• Polyarticular Juvenile Idiopathic Arthritis
• Giant Cell Arteritis
• Cytokine Release Syndrome
• COVID-19

Approved in United States as Actemra for:

• Rheumatoid Arthritis
• Systemic Juvenile Idiopathic Arthritis
• Polyarticular Juvenile Idiopathic Arthritis
• Giant Cell Arteritis
• Cytokine Release Syndrome
• COVID-19

Approved in Canada as Actemra for:

• Rheumatoid Arthritis
• Systemic Juvenile Idiopathic Arthritis
• Polyarticular Juvenile Idiopathic Arthritis
• Giant Cell Arteritis
• Cytokine Release Syndrome
• COVID-19

Approved in Japan as Actemra for:

• Rheumatoid Arthritis
• Systemic Juvenile Idiopathic Arthritis
• Polyarticular Juvenile Idiopathic Arthritis
• Giant Cell Arteritis
• Cytokine Release Syndrome
• COVID-19

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Findings from Research

Tocilizumab is a humanized monoclonal antibody that targets the interleukin-6 receptor, showing efficacy in treating conditions like Castleman disease and various types of arthritis, with approval in Japan and the European Union for these uses.

The drug is currently under review by the US FDA for moderate-to-severe rheumatoid arthritis and has potential applications for other IL-6 related disorders, such as Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab. Venkiteshwaran, A.[2021]

In a study of 53 patients with rheumatoid arthritis, tocilizumab (TCZ) demonstrated high effectiveness, with 75.5% achieving remission or low disease activity at 24 weeks and 87.3% at 52 weeks.

The switch from intravenous to subcutaneous administration of TCZ did not affect its effectiveness, and the treatment was found to be safe with a low adverse event rate of 13.6 events per 100 patient-years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of effectiveness, safety and optimization of tocilizumab in a cohort of patients with rheumatoid arthritis in clinical practice. Mena-Vázquez, N., Manrique-Arija, S., Rojas-Giménez, M., et al.[2022]

In a 2-year study involving 556 patients with active rheumatoid arthritis, tocilizumab (TCZ) combined with methotrexate was effective in achieving sustained remission, with 50.4% of patients able to discontinue TCZ after reaching this state.

While most patients (84.0%) who stopped TCZ experienced a flare in their condition, they responded well to reintroduction of the drug, and minimal radiographic progression was observed, indicating that TCZ is both effective and relatively safe for long-term management of rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and radiographic outcomes at 2 years and the effect of tocilizumab discontinuation following sustained remission in the second and third year of the ACT-RAY study. Huizinga, TW., Conaghan, PG., Martin-Mola, E., et al.[2022]

Tocilizumab is an effective treatment for systemic and polyarticular juvenile idiopathic arthritis (JIA) in children aged 2 years and older, showing significant improvement in patient responses compared to placebo in two phase III trials involving patients aged 2-17 years.

The drug was generally well tolerated, with infections being the most common adverse events; however, there was an approximately 11% annual risk of serious infections, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab: a review of its use in the treatment of juvenile idiopathic arthritis. Frampton, JE.[2021]

In a study of 188 patients aged 2-17 with polyarticular-course juvenile idiopathic arthritis (JIA), tocilizumab (TCZ) demonstrated high efficacy over 2 years, with JIA-ACR50/70/90 response rates of 80.3%, 77.1%, and 59.6% respectively, and over half of the patients achieving inactive disease by week 104.

The safety profile of TCZ was consistent with previous reports, with adverse event rates of 406.5 per 100 patient-years and serious infections at 5.2 per 100 patient-years, indicating that TCZ is a relatively safe option for long-term treatment of JIA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Tocilizumab for Polyarticular-Course Juvenile Idiopathic Arthritis in the Open-Label Two-Year Extension of a Phase III Trial. Brunner, HI., Ruperto, N., Zuber, Z., et al.[2021]

Tocilizumab, an interleukin-6 receptor antagonist, has shown significant clinical improvements in rheumatoid arthritis patients at doses greater than 4 mg/kg, with the most effective dose being 8 mg/kg, which also reduces joint damage as seen in radiographic measures.

While tocilizumab is effective, it is associated with common adverse effects such as liver function abnormalities, infections, and neutropenia, highlighting the need for further research to better understand its safety profile and optimal use in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab: an interleukin-6 receptor inhibitor for the treatment of rheumatoid arthritis. Plushner, SL.[2016]

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Clinical and radiographic outcomes at 2 years and the effect of tocilizumab discontinuation following sustained remission in the second and third year of the ACT-RAY study. [2022]

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Efficacy and Safety of Tocilizumab for Polyarticular-Course Juvenile Idiopathic Arthritis in the Open-Label Two-Year Extension of a Phase III Trial. [2021]

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