PROACTIVE: Preventing Acute/Chronic GVHD With TocIlizumab Combined With GVHD Prophylaxis Post allogEneic Transplant
Condition: Hematologic Malignancy
MeSH terms: Hematologic Neoplasms
Intervention: Tacrolimus; Methotrexate; Tocilizumab
Intervention description: 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.; 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.; 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.
Intervention MeSH terms: Methotrexate; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age ≥18 years.

          2. 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).

          3. Myeloablative conditioning (MAC) regimen, based on Center for International Blood and
             Marrow Transplant Research (CIBMTR) criteria.

          4. T cell-replete peripheral blood graft.

          5. 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).

          6. Cardiac function: Left ventricular ejection fraction ≥45% for myeloablative
             conditioning.

          7. Estimated creatinine clearance ≥40 mL/minute (using the Cockcroft-Gault formula and
             actual body weight).

          8. Pulmonary function: Diffusing capacity of the lungs for carbon monoxide (DLCO) ≥40%
             (adjusted for hemoglobin) and Forced Expiratory Volume (FEV1) ≥50%.

          9. Liver function: total bilirubin <3 x upper limit of normal and alanine
             aminotransferase (ALT) / aspartate aminotransferase (AST) <5 x upper normal limit.

         10. 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.

         11. Female patient: A negative pregnancy test will be required for women of child bearing
             potential. Breast-feeding or lactation is not permitted.

         12. Planned posttransplant maintenance therapy is allowed.

        Exclusion Criteria:

          1. Prior allogeneic HCT.

          2. Active central nervous system (CNS) involvement with malignancy.

          3. Patients receiving cord blood or haploidentical allograft.

          4. Patients undergoing in vivo or ex vivo T cell-depleted alloHCT.

          5. Karnofsky Performance Score <60%.

          6. 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.

          7. Active hepatitis B or C virus infection or known human immunodeficiency virus (HIV)
             positive.

          8. Prior intolerance or allergy to tocilizumab.

          9. Use of rituximab, alemtuzumab, anti-thymocyte globulin (ATG) or other monoclonal
             antibody planned as part of conditioning regimen for GVHD prophylaxis.

         10. History of diverticulitis, Crohn's disease or ulcerative colitis.

         11. History of demyelinating disorder.

         12. 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.

         13. Any serious medical or psychiatric illness that could, in the investigator's opinion,
             potentially interfere with the completion of treatment according to this protocol.