HIgh Dose Thymoglobulin Instead of Cyclosporine With a Low Dose of Thymoglobulin for GVHD Prophylaxis

NCT03456817 | Terminated Phase 2

• 1 other identifier: ATG2017
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out whether compared to our standard low dose ATG with CSA, the high dose ATG with low-dose CSA minimizes the chances of relapse and chronic GVHD, without increasing the chances of other transplant complications.

Conditions

Graft-versus-host-disease; Relapse

Outcome Measures

Primary Outcomes (1)

• moderate/severe chronic GVHD- and relapse-free survival (cGFRS) at 2 years post transplant

  cGRFS will be compared between the study patients and the historical/concurrent controls using a Cox proportional hazards model to determine if administering high dose ATG + MTX and low dose CSA will be associated with improved cGRFS compared to historical/concurrent controls (4.5 mg/kg ATG + MTX + CSA).

  2 years

Secondary Outcomes (1)

• quality of life

  approximately 2 years (21 to 27 months) post transplant

Study Arms (2)

Treatment Arm - High dose ATG, Low dose CSA

EXPERIMENTAL

High dose ATG will be infused on days -4, -3, -2, -1 and 0. Before each infusion of ATG (thymoglobulin), patient will receive medications preventing side effects from the ATG, including diphenhydramine (Benadryl), an antipyretic (ibuprofen or acetaminophen) and methylprednisolone (Solumedrol). The high dose ATG will be given into patient's vein via central venous catheter. Each infusion of ATG will take 4-8 hours. CSA (cyclosporine A) will be given from day 21. Standard dose methotrexate will be given.

Drug: Treatment Arm - high dose ATG

Control Arm - Standard of care

OTHER

Low dose ATG (thymoglobulin) will be infused on days -2, -1 and 0, and CSA (cyclosporine A) will be given from day -1 through day 84. Standard dose methotrexate will also be given.

Drug: Control Arm - standard of care

Interventions

Treatment Arm - high dose ATG DRUG

Patients agreeing to high dose ATG will be treated with 2 mg/kg daily on days -4 to 0. On days -4, -3 \& -2, ATG will be infused after fludarabine \& busulfan infusion. ATG will be infused over a minimum of 6 hrs on day -4 \& over at least 4 hrs on days -3, -2, -1 \& 0. Dose is based on actual body wt, \& rounded to nearest vial-Thymoglobulin is supplied in 25 mg vials, except if rounding would result in \>5% difference from calculated dose. Foothills Medical Center Unit 57 standard practice followed for ATG infusion. ATG premeds include methylprednisolone, diphenhydramine, and an antipyretic. Meperidine 25-50 mg IVPB every 4 hours will be given as needed for rigors. MTX is given 15 mg/m2 IV on day +1 \& 10 mg/m2 on days +3, +6 \& +11 posttransplant. First dose of methotrexate is given on day +1, at least 24 hrs following end of infusion of stem cell product.

Treatment Arm - High dose ATG, Low dose CSA

Control Arm - standard of care DRUG

The historical controls will have received and the concurrent controls will receive our standard GVHD prophylaxis, ie, ATG 4.5 mg/kg i.v. (0.5 mg/kg on day -2, 2.0 mg/kg on day -1 and 2.0 mg/kg on day 0), MTX (15 mg/m2 i.v. on day 1 and 10 mg/m2 i.v. on days 3, 6 and 11) and CSA (2.5 mg/kg twice a day i.v. starting from day -1, adjusting dose to target trough plasma CSA levels of 200-400 microg/L, switching to oral formulation before discharge from peritransplant hospitalization, targeting the trough plasma levels of 200-400 microg/L until day 56, and tapering to zero between day 56 and 84).

Control Arm - Standard of care

Eligibility Criteria

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

You may qualify if:

• First allogeneic HCT, performed for a hematologic malignancy, using filgrastim-mobilized peripheral blood stem cells (PBSC).
• Conditioning with fludarabine 50 mg/m2 daily on day -6 to -2, busulfan approximately 3.2 mg/kg daily on day -5 to -2 with PK adjustment (target AUC of 3750 uM\*min/L) and total body irradiation (TBI) 2 Gy x 2 given typically on day -1 and/or day 0 (before graft infusion), ie, our standard myeloablative conditioning.79 Dose and schedule adjustments per Investigator discretion are permitted.
• Planned GVHD prophylaxis with our standard of low-dose ATG (4.5 mg/kg) + MTX + high-dose CSA.
• HLA matched sibling donor, or ≥7/8 HLA allele-matched unrelated donor (maximum 1 allele mismatch at HLA-A, B, C, or DRB1).
• Age \>17 years.

You may not qualify if:

• Nonmyeloablative conditioning.
• Cord blood or marrow graft.
• Myelofibrosis being the primary indication for HCT.
• Previous autologous or allogeneic HCT.
• Total Bilirubin \>1.5-fold above upper normal limit (UNL), ALT \>2.0-fold above UNL, or alkaline phosphatase \>2.5-fold above UNL.
• HIV positive by a serologic test that includes detection of both antibody and antigen)
• Increased risk of tuberculosis, defined as patient requiring an anti-tuberculosis drug peritransplant. All patients with a history of tuberculosis (active or latent) or contact with a person with active tuberculosis will be evaluated by an infectious disease specialist to determine whether treatment or prophylaxis of tuberculosis with an anti-tuberculosis drug peritransplant is needed. The infectious disease specialist will order tests (eg, Mantoux tuberculin skin test or interferon gamma release test) as needed to arrive at the decision on whether an anti-tuberculosis drug peritransplant is needed.
• High risk of cytomegalovirus (CMV) disease or recurrent CMViremia based on donor negative AND recipient positive CMV serostatus.2 If recipient serostatus was determined since the presentation of his/her hematologic malignancy more than once and the results are discrepant, the determination performed \>4 weeks after a transfusion of platelets or plasma (or before transfusions of platelets or plasma were initiated) is considered valid. If unclear, the CMV serostatus determination will be at the discretion of the treating Investigator
• High risk of PTLD based on donor positive AND recipient negative Epstein-Barr virus (EBV) serostatus (EBNA1 or VCA IgG)80
• Hypersensitivity to rabbit blood protein, Thymoglobulin or a Thymoglobulin excipient.
• Severe obesity, defined as body mass index ≥40 kg/m2.81 The reason is that obese patients are at risk of achieving a high ATG area under the time vs concentration curve (AUC).82 This could lead to substantial toxicity (e.g., death due to an infection) when using the studied high dose (10 mg/kg) of ATG.
• Contraindication to methotrexate:
• Hypersensitivity to methotrexate or to any ingredient in the formulation or component of the container.
• Females of childbearing potential who are pregnant, breastfeeding or unwilling to use adequate contraception from the time of enrolment until at least day 100 posttransplant.

Sponsors & Collaborators

• AHS Cancer Control Alberta: lead

Study Sites (1)

Tom Baker Cancer Centre/Arthur J.E. Child Comprehensive Cancer Centre

Calgary, Alberta, Canada

Location

MeSH Terms

Conditions

Graft vs Host Disease; Recurrence

Condition Hierarchy (Ancestors)

Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jan Storek, MD

  Tom Baker Cancer Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2018
• First Posted: March 7, 2018
• Study Start: July 1, 2020
• Primary Completion: May 31, 2025
• Study Completion: May 31, 2025
• Last Updated: July 18, 2025

Record last verified: 2025-07

Locations

CA (1)