Tocilizumab for the Prevention of Graft Versus Host Disease After Cord Blood Transplantation

NCT03434730 | Completed Phase 2 FDA Drug

• 1 other identifier: 17-616
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the research in this study is to make participants' transplant safer by reducing the risk of developing GVHD and GVHD-related complications by giving participants a dose of the drug tocilizumab in addition to the standard approach for GVHD prevention. Tocilizumab reduces the risk of inflammation by blocking the effect of Interleukin-6, a protein that exists in high levels in the blood when there is inflammation. Participants who receive stem cell transplants have high levels of this protein in their blood early after transplant. Therefore, the goal of this study is to reduce the risk of inflammation after transplant with the addition of Tocilizumab. This could decrease the risk of developing GVHD and GVHD-associated complications.

Conditions

Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Acute Leukemia; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Myeloproliferative Disorder; Non Hodgkin Lymphoma; Hodgkin Lymphoma; Leukemia

Keywords

tocilizumab; 17-616; Memorial Sloan Kettering Cancer Center

Outcome Measures

Primary Outcomes (1)

• Incidence of grade II-IV aGVHD by day 100 after study treatment

  100 days post treatment

Study Arms (1)

Adult Participants With High Risk Hematologic Malignancies

EXPERIMENTAL

Radiation: Total Body Irradiation; Drug: Cyclosporine; Drug: Mycophenolate Mofetil; Drug: Tocilizumab; Drug: Filgrastim

Interventions

Total Body Irradiation RADIATION

Participants will receive a total dose of 400 cGy on day -2 and day -1 as 2 fractions (200 cGy x 2). Participants receiving total body irradiation (TBI) are treated in a standing position, and the treatment takes about 20 to 30 minutes.

Also known as: TBI

Adult Participants With High Risk Hematologic Malignancies

Cyclosporine DRUG

Dilute in D5W or NS to make a 2.5 mg/ ml solution. Infuse slowly over approximately 1-4 hours (intermittent infusion) or 24 hours for continuous infusion.

Also known as: Sandimmune

Adult Participants With High Risk Hematologic Malignancies

Mycophenolate Mofetil DRUG

A 1000 mg dose should be placed in 140 ml of D5W. Administer only with D5W, over at least 2 hours.

Also known as: CellCept

Adult Participants With High Risk Hematologic Malignancies

Tocilizumab DRUG

For participants \< 30kg, dilute with 50mL 0.9% sodium chloride. For participants ≥ 30kg, dilute to 100ml with 0.9% sodium chloride. Administer infusion over 60 minutes with infusion set.

Also known as: Acemtra

Adult Participants With High Risk Hematologic Malignancies

Filgrastim DRUG

The single use prefilled syringes contain either 300 mcg or 480 mcg Filgrastim at a fill volume of 0.5 mL or 0.8 mL, respectively. For the prevention/treatment of chemotherapy induced neutropenia, the dose of filgrastim is standardized per body weight: ≤ 60 kg = 300 mcg daily subcutaneously; \> 60 kg = 480 mcg subcutaneously daily.

Also known as: Granulocyte-Colony Stimulating Factor, Neupogen

Adult Participants With High Risk Hematologic Malignancies

Eligibility Criteria

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

You may qualify if:

• I. Acute myelogenous leukemia (AML)
• Complete first remission (CR1) at high risk for relapse such as any of the following:
• Known prior diagnosis of myelodysplasia (MDS) or myeloproliferative disorder
• Therapy-related AML
• White cell count at presentation \> 100,000
• Presence of extramedullary leukemia at diagnosis
• Any unfavorable subtype by FAB or WHO classification
• High-risk cytogenetics (e.g. those associated with MDS, abnormalities of 5, 7, 8, complex karyotype) or high risk molecular abnormalities
• Requirement for 2 or more induction to achieve CR1
• Any patient with newly diagnosed AML with intermediate risk cytogenetics who elects allograft with curative intent over consolidation chemotherapy
• Any patient unable to tolerate consolidation chemotherapy as would have been deemed appropriate by the treating physician
• Other high risk features not defined above
• Complete second remission (CR2)
• Primary refractory or relapsed AML with less than 10% blasts before transplant. Persistent/relapsed AML with cytogenetic, flow cytometric, or molecular aberrations in \>/= 10% of cells are eligible
• II. Acute lymphoblastic leukemia (ALL)

You may not qualify if:

• Indolent NHL or Hodgkin lymphoma with POD after most recent salvage chemotherapy
• Diagnosis of myelofibrosis or other malignancy with moderate-severe bone marrow fibrosis
• Any diagnosis without prior immunosuppressive chemotherapy within 3 months of intended admission for transplant
• Prior checkpoint inhibitors/ blockade in the last 12 months
• Two prior stem cell transplants of any kind
• One prior autologous stem cell transplant within the preceding 12 months
• One prior allogeneic stem cell transplant within the preceding 24 months
• Prior radiation therapy with 400cGy or more of TBI
• Active and uncontrolled infection at time of transplantation
• HIV infection
• Seropositivity for HTLV-1.
• Inadequate performance status/ organ function.
• Pregnancy or breast feeding
• Patient or guardian unable to give informed consent or unable to comply with the treatment protocol including appropriate supportive care, long-term follow-up, and research tests.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• Politikos I, Brown S, Fein JA, Eng S, Casem K, Chinapen S, Quach S, Scaradavou A, Cho C, Dahi P, Giralt SA, Gyurkocza B, Hanash AM, Jakubowski AA, Papadopoulos EB, Perales MA, Ponce DM, Shaffer BC, Tamari R, Young JW, Devlin S, Peled JU, Barker JN. Phase 2 trial of cyclosporine-A, mycophenolate mofetil, and tocilizumab GVHD prophylaxis in cord blood transplantation. Blood Adv. 2025 May 27;9(10):2570-2584. doi: 10.1182/bloodadvances.2024014177.

  PMID: 40423982 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Myeloproliferative Disorders; Lymphoma, Non-Hodgkin; Hodgkin Disease; Leukemia

Interventions

Whole-Body Irradiation; Cyclosporine; Mycophenolic Acid; tocilizumab; Filgrastim; Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Lymphoma

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Investigative Techniques; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Proteins; Biological Factors

Study Officials

• Ioannis Politikos, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2018
• First Posted: February 15, 2018
• Study Start: February 7, 2018
• Primary Completion: April 18, 2025
• Study Completion: April 18, 2025
• Last Updated: April 22, 2025

Record last verified: 2025-04

Locations

US (1)