A Study of Tacrolimus/Methotrexate and Tocilizumab to Prevent Acute Graft-Versus-Host Disease (AGVD) After Allogeneic Hematopoietic Stem Cell Transplant

NCT02206035 | Completed Phase 2 Results FDA Drug

• 1 other identifier: PRO00023000
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II open label trial designed to evaluate the efficacy of Tac/MTX/Toc in preventing graft versus host disease (GVHD). Outcomes of patients on this clinical trial will be compared to those of contemporary controls from the CIBMTR.

Conditions

Hematopoietic Stem Cell Transplantation

Outcome Measures

Primary Outcomes (1)

• Number of Subjects Not Experiencing Grade II-IV Acute Graph Versus Host Disease (aGVHD)

  This measure is the number of subjects who did not experience grade II-IV aGVHD at or before day 180 comparing recipients of tacrolimus (Tac), methotrexate (MTX), and tocilizumab (Toc) to a contemporary control population abstracted from a database maintained by the Center for International Blood and Marrow Transplant Research (CIBMTR). The staging of aGVHD was according to the criteria of Przepiorka, et al., 1995 which assigns a score to the clinical status of multiple organ systems aggregated to determine the clinical stage. A higher stage indicates more severe aGVHD symptoms and poorer clinical outcome.

  Day 180

Secondary Outcomes (5)

• Score of Depressive Symptoms Using General Depressive Subscale of the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument

  Baseline, Day 28, Day 100 and Day 180

• Score of Anxiety Symptoms Using the Inventory of Depression and Anxiety Symptoms (IDAS) Instrument

  Baseline, Day 28, Day 100 and Day 180

• Score of Fatigue Symptoms Using the Fatigue Symptom Inventory (FSI) Instrument

  Baseline, Day 28, Day 100 and Day 180

• Score of Sleep Symptoms Using the Pittsburgh Sleep Quality Index (PSQI) Instrument

  Baseline, Day 28, Day 100 and Day 180

• Score of Pain Symptoms Using the Brief Pain Inventory (BPI) Instrument (Interference)

  Baseline, Day 28, Day 100 and Day 180

Study Arms (1)

Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)

EXPERIMENTAL

Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant. Methotrexate will be dosed at 15 mg/m2 Day +1 and 10mg/m2 Days +3, +6 and +11. Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1

Drug: Tacrolimus; Drug: Methotrexate; Drug: Tocilizumab

Interventions

Tacrolimus DRUG

Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant.

Also known as: fujimycin, FK506

Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)

Methotrexate DRUG

Methotrexate will be dosed at 15 mg/m2 Day +1 and 10mg/m\^2 Days +3, +6 and +11.

Also known as: Trexall

Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)

Tocilizumab DRUG

Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1.

Also known as: Actemra

Tacrolimus, Methotrexate and Tocilizumab (Tac/MTX/Toc)

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 acute leukemia, chronic myelogenous leukemia, myeloproliferative disease and myelodysplasia with less than 5% of blasts in the bone marrow
• Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, Non-Hodgkin Lymphoma or Hodgkin Disease with chemosensitive disease at time of transplant
• Planned conditioning regimens including combination of busulfan and fludarabine or busulfan and cyclophosphamide
• Transplantation with T-cell-replete grafts
• Bone marrow or mobilized peripheral blood cell grafts
• Patients must have either a sibling donor (6/6 match at human leukocyte antigens (HLA-A, -B and -DRB1) or a unrelated donor (8/8 match at HLA-A, -B, -C and -DRB1)
• Cardiac function: Ejection fraction at rest \>45% for myeloablative conditioning or \>40% for reduced intensity conditioning
• Estimated creatinine clearance greater than 50 mL/minute (using the Cockcroft-Gault formula and actual body weight)
• Pulmonary function: Diffusing Capacity of Lung for Carbon Monoxide (DLCO) ≥40% (adjusted for hemoglobin) and FEV1≥50%
• Liver function: total bilirubin \< 1.5 x the upper limit of normal and alanine aminotransferase (ALT) / aspartate aminotransferase (AST) \< 2.5x the upper normal limit
• Signed informed consent

You may not qualify if:

• Prior allogeneic hematopoietic cell transplant (HCT)
• Karnofsky Performance Score \<70%
• Patients with uncontrolled bacterial, viral or fungal infections (currently taking medication and with progression of infectious disease or no clinical improvement) at time of enrollment
• Prior intolerance or allergy to Tocilizumab
• Use of rituximab, alemtuzumab, anti-thymocyte globulin (ATG) or other monoclonal antibody at time of conditioning regimen
• History of diverticulitis, Crohn's disease or ulcerative colitis
• History of demyelinating disorder
• Pregnant and lactating women
• Patients with a history of rheumatologic disorders who have previously received Tocilizumab
• Eligibility for the Control Arm
• Receive Tac/MTX as the sole GVHD prophylaxis approach
• Receive the same regimens as specified in Table 2.5
• Year of transplant from 2010 to 2013
• \. Karnofsky Performance Score \< 70%
• Data for all eligible patients will be used to constitute the control database for this study

Sponsors & Collaborators

• William R. Drobyski, MD: lead

Study Sites (1)

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (7)

• Watson D, O'Hara MW, Simms LJ, Kotov R, Chmielewski M, McDade-Montez EA, Gamez W, Stuart S. Development and validation of the Inventory of Depression and Anxiety Symptoms (IDAS). Psychol Assess. 2007 Sep;19(3):253-68. doi: 10.1037/1040-3590.19.3.253.

  PMID: 17845118 BACKGROUND

• D'Souza A, Lee S, Zhu X, Pasquini M. Current Use and Trends in Hematopoietic Cell Transplantation in the United States. Biol Blood Marrow Transplant. 2017 Sep;23(9):1417-1421. doi: 10.1016/j.bbmt.2017.05.035. Epub 2017 Jun 9.

  PMID: 28606646 BACKGROUND

• Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995 Jun;15(6):825-8.

  PMID: 7581076 BACKGROUND

• Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, Palmer J, Weisdorf D, Treister NS, Cheng GS, Kerr H, Stratton P, Duarte RF, McDonald GB, Inamoto Y, Vigorito A, Arai S, Datiles MB, Jacobsohn D, Heller T, Kitko CL, Mitchell SA, Martin PJ, Shulman H, Wu RS, Cutler CS, Vogelsang GB, Lee SJ, Pavletic SZ, Flowers ME. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015 Mar;21(3):389-401.e1. doi: 10.1016/j.bbmt.2014.12.001. Epub 2014 Dec 18.

  PMID: 25529383 BACKGROUND

• Hann DM, Jacobsen PB, Azzarello LM, Martin SC, Curran SL, Fields KK, Greenberg H, Lyman G. Measurement of fatigue in cancer patients: development and validation of the Fatigue Symptom Inventory. Qual Life Res. 1998 May;7(4):301-10. doi: 10.1023/a:1024929829627.

  PMID: 9610214 BACKGROUND

• Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213. doi: 10.1016/0165-1781(89)90047-4.

  PMID: 2748771 BACKGROUND

• Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singap. 1994 Mar;23(2):129-38.

  PMID: 8080219 BACKGROUND

MeSH Terms

Interventions

Tacrolimus; Methotrexate; tocilizumab

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

wdrobysk@mcw.edu

414-456-4941

Study Officials

• William Drobyski, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

• Marcelo Pasquini, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

• Jennifer Knight, 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: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 30, 2014
• First Posted: August 1, 2014
• Study Start: December 1, 2014
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2018
• Last Updated: March 9, 2023
• Results First Posted: March 9, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)