Tocilizumab for the Prevention of Graft Failure and GVHD in Haplo-Cord Transplantation
Condition: Hematologic Malignancy; Bone Marrow Transplant
MeSH terms: Neoplasms; Hematologic Neoplasms
Intervention: Tocilizumab; Fludarabine; Melphalan; Anti-thymocyte globulin (rabbit); Total Body Irradiation
Intervention description: Tocilizumab 8 mg/kg intravenously administered as a single dose on Day -1 of transplant conditioning regimen; Fludarabine 30 mg/m2 intravenously administered on Day -7, Day -6, Day -5, Day -4, Day -3 of transplant conditioning regimen if under the age of 60. If over the age of 60, Fludarabine 30 mg/m2 intravenously administered on Day -5, Day -4 and Day -3 of transplant conditioning regimen.; Melphalan 140 mg/m2 intravenously administered on Day -2 of transplant conditioning regimen.; Anti-thymocyte globulin (ATG) 1.5 mg/kg; Total Body Irradiation (TBI) 2 Gray, administered on Day -4 and Day -3 of transplant conditioning regimen
Intervention MeSH terms: Fludarabine; Melphalan; Thymoglobulin; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Tocilizumab; Haplo-Cord Transplant; Allogeneic Transplant; Hematologic Malignancies

Summary:

      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:

        Inclusion Criteria:

          1. Subject must have a confirmed diagnosis of one of the following:

               1. Relapsed or refractory acute leukemia (myeloid or lymphoid)

               2. Acute leukemia in first remission at high-risk for recurrence

               3. Chronic myelogenous leukemia in chronic, accelerated phase or blast-crisis

               4. Myelodysplastic syndromes

               5. Chronic myeloproliferative disease

               6. Recurrent, refractory or high-risk malignant lymphoma

               7. Chronic lymphocytic leukemia, relapsed or with poor prognostic features

               8. Multiple myeloma

               9. Other hematological disorder in need of allogeneic transplant (e.g. blastoid
                  dendritic cell neoplasm)

          2. Age ≥ 18 years.

          3. Likely to benefit from allogeneic transplant in the opinion of the transplant
             physician.

          4. An HLA-identical related or unrelated donor cannot be identified within an appropriate
             time frame.

          5. Karnofsky Performance Status (KPS) of ≥ 70%.

          6. Acceptable organ function as defined below:

               1. Serum bilirubin: <2.0 mg/dL

               2. ALT (SGPT) <3x upper limit of normal (ULN)

               3. Creatinine Clearance: >50 mL/min/1.73m2 (eGFR as estimated by the modified MDRD
                  equation)

               4. Left ventricular ejection fraction >40%

               5. Pulmonary diffusion capacity >40% predicted

          7. Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          1. Life expectancy is severely limited by concomitant illness or uncontrolled infection.

          2. Evidence of chronic active hepatitis or cirrhosis

          3. Uncontrolled HIV disease.

          4. Pregnancy or lactation.

          5. History of complicated diverticulitis, including fistulae, abscess formation or
             gastrointestinal perforation

          6. 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.