Preemptive Therapy of GVHD

NCT01994824 | Terminated Phase 2

• 1 other identifier: PreemptiveATG
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Graft-vs-host disease (GVHD) causes substantial mortality, morbidity and poor quality of life after blood or marrow transplantation (BMT). In Alberta, we use antithymocyte globulin (ATG, given on days -2, -1 and 0) in addition to methotrexate and cyclosporine for GVHD prophylaxis. In spite of that, \~40% patients develop significant GVHD (grade 2-4 acute GVHD or chronic GVHD needing systemic immunosuppressive therapy). ATG at the dose we typically use (4.5 mg/kg) is relatively non-toxic. At higher doses, ATG could increase the likelihood of posttransplant infections or relapse. Thus an extra dose of ATG (on top of the routine 4.5 mg/kg) might be justified only for patients at high risk of developing significant GVHD. In our experience, low serum level of interleukin-15 (IL15) and high serum level of interleukin-2 receptor alpha (IL2Ra) on day 7 predict development of significant GVHD. Here we will test whether, compared to historical/concurrent controls, an extra dose of ATG (3 mg/kg on day 8) given to patients with low IL15 or high IL2Ra on day 7 reduces the incidence of significant GVHD, and improves survival free of relapse and GVHD, and quality of life.

Conditions

Graft-vs-host Disease

Outcome Measures

Primary Outcomes (1)

• Cumulative incidence of significant GVHD

  2 years

Secondary Outcomes (2)

• Survival free of relapse and significant GVHD

  2 years

• Quality of life measured by SF36

  2 years

Study Arms (1)

Intervention arm

EXPERIMENTAL

Transplant recipients will have IL15 and IL2Ra measured on day 7. If at risk for significant GVHD, the patient will get rabbit antithymocyte globulin, 3 mg/kg on day 8. Patients from this intervention/experimental arm will be compared to historical and concurrent controls (no ATG on day 8).

Drug: rabbit antithymocyte globulin

Interventions

rabbit antithymocyte globulin DRUG

Thymoglobulin, 3 mg/kg, will be given on day 8 posttransplant to patients at high risk of significant GVHD per day 7 IL15 and IL2Ra levels.

Also known as: Thymoglobulin

Intervention arm

Eligibility Criteria

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

You may qualify if:

• First allogeneic hematopoietic cell transplantation (second transplants are rare, typically performed for relapse of leukemia, in which case the likelihood of relapse is high, and there is the theoretical risk of increasing the likelihood further with ATG).
• Conditioning including ATG 4.5 mg/kg (the predictive value of IL15 and IL2Ra levels was determined in patients whose conditioning included 4.5 mg/kg or ATG).
• Age \>17 (the predictive value of IL15 and IL2Ra levels has not been studied in children).

You may not qualify if:

• Nonmyeloablative conditioning (possible risk of ATG increasing relapse).
• Active viral infection (risk of worsening of the viral infection with ATG).
• Neutropenic fever with hypotension. In such case, the ATG can be given on day 9 (instead of day 8) if patient no longer has hypotension.
• Hypoxemia. In such case, the ATG can be given on day 9 (instead of day 8) if patient no longer has hypoxemia.
• History of anaphylactic reaction to Thymoglobulin or another rabbit blood protein.

Sponsors & Collaborators

• University of Calgary: lead
• University of Alberta: collaborator
• Alberta Health services: collaborator

Study Sites (1)

Alberta Health Services-CancerControl / University of Calgary / University of Alberta (Edmonton)

Calgary, Alberta, T2N 4N1, Canada

Location

Related Publications (1)

• Khanolkar RA, Kalra A, Kinzel M, Pratt LM, Dharmani-Khan P, Chaudhry A, Williamson TS, Daly A, Morris DG, Khan FM, Storek J. A biomarker-guided, prospective, phase 2 trial of pre-emptive graft-versus-host disease therapy using anti-thymocyte globulin. Cytotherapy. 2021 Nov;23(11):1007-1016. doi: 10.1016/j.jcyt.2021.06.003. Epub 2021 Aug 6.

  PMID: 34373186 DERIVED

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

thymoglobulin

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• Jan Storek, MD, PhD

  University of Calgary

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 20, 2013
• First Posted: November 26, 2013
• Study Start: January 1, 2014
• Primary Completion: June 30, 2017
• Study Completion: September 27, 2021
• Last Updated: November 30, 2023

Record last verified: 2023-11

Locations

CA (1)