PROACTIVE: Preventing Acute/Chronic GVHD With TocIlizumab Combined With GVHD Prophylaxis Post allogEneic Transplant

NCT03699631 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: PRO326941K08HL143189-01A15P30CA008748
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II open-label trial designed to evaluate the efficacy of tocilizumab in improving GVHD-free/relapse-free survival (GRFS) after allogeneic hematopoietic cell transplantation (alloHCT) for hematologic malignancy.

Conditions

Hematologic Malignancy

Outcome Measures

Primary Outcomes (1)

• The Number of Patients With GVHD/Relapse-free (GRFS) Survival

  GRFS is defined as survival without grade III-IV acute graft versus host disease (GVHD), systemic therapy requiring chronic GVHD, relapse, or death at 12 months after matched related/unrelated donor bone marrow or peripheral blood allogeneic hematopoietic cell transplantation (alloHCT) using myeloablative conditioning (MAC). Patients who are alive without GVHD will be censored at the last follow-up.

  Day 365

Study Arms (1)

Tacrolimus/Methotrexate/Tocilizumab

EXPERIMENTAL

Patients enrolled on the clinical trial will receive tacrolimus initiating at Day -1 at doses to maintain therapeutic levels per institutional preference and continued until at least Day +90 post-transplant. Methotrexate will be administered intravenously and dosed at 15 mg/m2 Day +1 and 10 mg/m2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg on Day -1 and at day +100 (+/- 14 days).

Drug: Tacrolimus; Drug: Methotrexate; Drug: Tocilizumab

Interventions

Tacrolimus DRUG

Tacrolimus will be given intravenously at a dose of 0.03 mg/kg/day starting Day -3. Subsequent dosing will be based on blood levels.

Also known as: Prograf

Tacrolimus/Methotrexate/Tocilizumab

Methotrexate DRUG

Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic cell infusion.

Also known as: Trexall

Tacrolimus/Methotrexate/Tocilizumab

Tocilizumab DRUG

Tocilizumab will be administered intravenously (IV) at a dose of 8 mg/kg (maximum dose of 800 mg) once on the Day -1 approximately 24 hours prior to the estimated time of the hematopoietic cell infusion, and subsequently, on Day +100 (+/- 14 days, i.e., Days +86 to +114) post-alloHCT. The infusion will be administered over 60 minutes through a dedicated IV line and must not be administered by IV bolus.

Also known as: Actemra

Tacrolimus/Methotrexate/Tocilizumab

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years.
• Patients with any hematologic malignancy for which alloHCT is indicated. Patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) must be in complete remission at the time of alloHCT(\<5% blasts in the bone marrow, normal maturation of all cellular components in the bone marrow and absence of extramedullary disease).
• Myeloablative conditioning (MAC) regimen, based on Center for International Blood and Marrow Transplant Research (CIBMTR) criteria.
• T cell-replete peripheral blood graft.
• Patients must have a matched related or unrelated donor (at least 6/6 match at human leukocyte antigens (HLA) -A, -B and -C for related donors and at least 8/8 match at HLA-A, -B, -C and -DRB1 for unrelated donors).
• Cardiac function: Left ventricular ejection fraction ≥45% for myeloablative conditioning.
• Estimated creatinine clearance ≥40 mL/minute (using the Cockcroft-Gault formula and actual body weight).
• Pulmonary function: Diffusing capacity of the lungs for carbon monoxide (DLCO) ≥40% (adjusted for hemoglobin) and Forced Expiratory Volume (FEV1) ≥50%.
• Liver function: total bilirubin \<3 x upper limit of normal and alanine aminotransferase (ALT) / aspartate aminotransferase (AST) \<5 x upper normal limit.
• Signed informed consent: Voluntary written consent must be given before patient registration and performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
• Female patient: A negative pregnancy test will be required for women of child bearing potential. Breast-feeding or lactation is not permitted.
• Planned posttransplant maintenance therapy is allowed.

You may not qualify if:

• Prior allogeneic HCT.
• Active central nervous system (CNS) involvement with malignancy.
• Patients receiving cord blood or haploidentical allograft.
• Patients undergoing in vivo or ex vivo T cell-depleted alloHCT.
• Karnofsky Performance Score \<60%.
• Patients with uncontrolled bacterial, viral or fungal infections (currently on treatment and with progression of infectious disease or no clinical improvement) at time of enrollment.
• Active hepatitis B or C virus infection or known human immunodeficiency virus (HIV) positive.
• Prior intolerance or allergy to tocilizumab.
• Use of rituximab, alemtuzumab, anti-thymocyte globulin (ATG) or other monoclonal antibody planned as part of conditioning regimen for GVHD prophylaxis.
• History of diverticulitis, Crohn's disease or ulcerative colitis.
• History of demyelinating disorder.
• Any current uncontrolled cardiovascular conditions, including uncontrolled ventricular arrhythmias, New York Heart Association (NYHA) class III or IV congestive heart failure, uncontrolled angina, or electrocardiographic evidence of active ischemia or active conduction system abnormalities.
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.

Sponsors & Collaborators

• Medical College of Wisconsin: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Chhabra S, Szabo A, Clurman A, McShane K, Waters N, Eastwood D, Samanas L, Fei T, Armijo G, Abedin S, Longo W, Hari P, Hamadani M, Shah NN, Runaas L, Jerkins JH, Van den Brink M, Peled JU, Drobyski WR. Mitigation of gastrointestinal graft-versus-host disease with tocilizumab prophylaxis is accompanied by preservation of microbial diversity and attenuation of enterococcal domination. Haematologica. 2023 Jan 1;108(1):250-256. doi: 10.3324/haematol.2022.281309. No abstract available.

  PMID: 36106394 RESULT

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

Tacrolimus; Methotrexate; tocilizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: William Drobyski, MD
• Organization: Froedtert and the Medical College of Wisconsin

wdrobyski@mcw.edu

414-805-6700

Study Officials

• William R Drobyski, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 5, 2018
• First Posted: October 9, 2018
• Study Start: November 6, 2018
• Primary Completion: March 2, 2022
• Study Completion: April 1, 2023
• Last Updated: April 19, 2023
• Results First Posted: April 19, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)