Abatacept as GVHD Prophylaxis Phase 2

NCT01743131 | Completed Phase 2 Results DMC

• 3 other identifiers: IRB00058187Abatacept Phase 2, Aba2R01FD004099
• Study Type: interventional
• Target: 186
• Locations: 2 countries
• Sites: 14

Brief Summary

This is a phase II multi-center, randomized, double blind, placebo-controlled trial. The investigators are doing this study to see if a new drug, abatacept, can be used together with a calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate to provide better protection against Acute Graft versus Host Disease (aGvHD) without causing more infections.

Conditions

Graft vs Host Disease; Malignancy

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Cumulative Incidence of Severe aGVHD at Day +100 Post-transplant

  The primary analysis will consist of estimating the cumulative incidence of severe aGVHD at day +100 post-transplant in the standard and investigational study arms. All registered patients will be considered for this analysis. The primary null hypothesis of the study is that there will be no difference in severe aGVHD between the investigational and standard GVHD prophylaxis arms. The primary outcome will be assessed in a final analysis to be performed after the last enrolled patient has been followed for 100 days post-transplant. The cumulative incidence and confidence interval will be calculated. The cumulative incidence will be compared between treatment arms using logistic regression models. Relapse will be considered a competing risk for aGVHD to negate the effect of measures, such as withdrawal of immune suppression and donor-lymphocyte infusion, often used in response to relapse.

  First 100 days after transplant

Secondary Outcomes (3)

• A Cumulative Incidence of Relapse, Non-relapse Mortality, Acute GVHD Grade III-IV, cGVHD Requiring Systemic Therapy, Overall Survival and GRFS Will be Computed.

  5 years post-transplant

• Percentage of Participants With Severe (Grade III-IV) aGVHD Free Survival (GFS) up to Day +180

  First 180 days after transplant

• Rate of Severe (Grade III-IV) aGVHD (Based on Adjudicated aGVHD Events) up to Day +180

  First 180 days after transplant

Study Arms (2)

Standard GVHD Prophylxis + Placebo

PLACEBO COMPARATOR

Standard GVHD prophylaxis and placebo. Standard GVHD prophylaxis is calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.

Drug: placebo

Standard GVHD Prophylxis + Abatacept

EXPERIMENTAL

Standard GVHD prophylaxis and abatacept (investigational product). Standard GVHD prophylaxis is calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate.

Drug: Abatacept

Interventions

Abatacept DRUG

Arm B-investigational prophylaxis with abatacept, a calcineurin inhibitor and methotrexate

Also known as: Orencia

Standard GVHD Prophylxis + Abatacept

placebo DRUG

Standard GVHD Prophylxis + Placebo

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be at least 6 years old and weigh 20 kg.
• Must have a willing unrelated adult donor (bone marrow or peripheral blood). Donors may have a single mismatch (i.e. be a 7/8) and this mismatch may be at the allele or antigen level; however, donors with allele level disparity should be given preference over those with antigen level disparity. The use of mismatched donors in which disparity is only in the host versus graft direction (because of recipient homozygosity) is discouraged because of the potentially heightened risk for graft rejection. Centers may perform extended typing (e.g. DQB1 and DPB1) according to institutional practices and use these results in selecting donors; however, it is recommended that this extending typing be used only to select between donors who are equally well matched with the recipient at the A, B, C and DRB1.
• All patients and/or their parents or legal guardians must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
• Must have a high risk hematologic malignancy as defined below:
• Acute myeloid leukemia (AML).
• Myelodysplastic syndrome
• (i) Adult patients (≥21 years) must meet criteria for intermediate, high or very high-risk disease based on the World Health Organization classification based prognostic scoring system.
• Intermediate risk (2 points), high risk (3-4 points), very high risk (4-5 points)
• RA = refractory anemia, RARS = refractory anemia with ringed sideroblasts, RCMD = refractory cytopenia with multilineage dysplasia, RCMD-RS = refractory cytopenia with multilineage dysplasia and ringed sideroblasts, RAEB-1 = refractory anemia with excess of blasts-1 (5-9% blasts), RAEB-2 = refractory anemia with excess of blasts-2 (10-19% blasts).
• \*Karyotype: Good = normal, -Y, del(5q), del(20q), Poor = complex (≥ 3 abnormalities), chromosome 7 anomalies, Intermediate = other abnormalities.
• \*RBC transfusion requirement = having ≥ 1 RBC transfusion every 8 weeks over a 4-month period.
• (ii) Pediatric patients with MDS, regardless of subtype, will be eligible.
• (c) Acute lymphoblastic leukemia (ALL). (i) Given the poor prognosis of adults (≥21 years) with ALL, adults in 1st or greater complete remission will be eligible.. CR is defined as an M1 marrow (\<5% blasts), no evidence of extramedullary disease, and an absolute neutrophil count ≥ 1.0 x 109/L. Complete remissions without platelet recovery (CRp) will be considered remissions (ii) Given the generally good prognosis of children (\<21 years) with ALL, they will have to meet one of the criteria listed below. Additionally, children who are enrolled on a COG ALL trial for newly diagnosed or relapsed disease will have to meet the criteria for BMT outlined in that trial. CR is defined as an M1 marrow (\<5% blasts), no evidence of extramedullary disease, and an absolute neutrophil count ≥ 1.0 x 109/L. Complete remissions without platelet recovery (CRp) will be considered remissions.
• In 1st complete remission with a very high risk for relapse.
• Haplodiploidy (\<44 chromosomes)

You may not qualify if:

• Prior allogeneic HSCT.
• The patient is enrolled on a COG trial that uses criteria for unrelated donor HSCT, which conflict with our eligibility criteria.
• The patient is enrolled on a COG trial that utilizes unrelated donor HSCT and requires that patients be transplanted using an approach specified by the protocol that is in conflict with the approach specified in this protocol.
• Availability of a willing and suitable HLA identical related donor.
• Uncontrolled viral, bacterial, fungal or protozoal infection at the time of study enrollment.
• HIV infection.
• Serious psychiatric disease including schizophrenia, bipolar disorder and severe depression.
• Any patient with a known or suspected inherited predisposition to cancer should be discussed with the study team prior to screening for eligibility.
• Patients with a known inherited or constitutional predisposition to transplant morbidities, including, but not limited to Fanconi Anemia, Dyskeratosis Congenita, Shwachman-Diamond Syndrome and Down Syndrome will be excluded.
• Patients with known inherited or constitutional predisposition to non-hematologic cancers including, but not limited to Li-Fraumeni syndrome, BRCA1 and BRCA2 mutations will be excluded.
• Patients with an inherited predisposition to leukemia or otherwise hematologic malignancies that have not been associated with predisposition to transplant morbidities or non-hematologic cancers will not be excluded.
• Known inherited or constitutional predisposition to cancer including, but not limited to Li-Fraumeni syndrome, Down syndrome and BRCA1 and BRCA2 mutations.
• Incompletely treated active tuberculosis Infection.
• Pregnancy (positive serum b-HCG) or breastfeeding.
• Estimated GFR of \< 50 mL/min/1.73m2.

Sponsors & Collaborators

• Boston Children's Hospital: lead
• FDA Office of Orphan Products Development: collaborator

Study Sites (14)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Children's Healthcare of Atlanta at Egleston

Atlanta, Georgia, 30322, United States

Location

Emory University/Winship Cancer Center

Atlanta, Georgia, 30322, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Washington University

St Louis, Missouri, 63141, United States

Location

Michael Grimley

Cincinnati, Ohio, 45229, United States

Location

University of Utah

Salt Lake City, Utah, 84113, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98101, United States

Location

Children's and Women's Health Center of BC

Vancouver, British Columbia, V6H 3V4, Canada

Location

Related Publications (2)

• Takahashi T, Watkins B, Bratrude B, Neuberg D, Hebert K, Betz K, Yu A, Choi SW, Davis J, Duncan C, Giller R, Grimley M, Harris AC, Jacobsohn D, Lalefar N, Farhadfar N, Pulsipher MA, Shenoy S, Petrovic A, Schultz KR, Yanik GA, Blazar BR, Horan JT, Langston A, Kean LS, Qayed M. The Adverse Event Landscape of Stem Cell Transplant: Evidence for AGVHD Driving Early Transplant Associated Toxicities. Transplant Cell Ther. 2025 Feb;31(2):109.e1-109.e13. doi: 10.1016/j.jtct.2024.03.030. Epub 2024 Apr 6.

  PMID: 38583802 DERIVED

• Takahashi T, Al-Kofahi M, Jaber M, Bratrude B, Betz K, Suessmuth Y, Yu A, Neuberg DS, Choi SW, Davis J, Duncan C, Giller R, Grimley M, Harris AC, Jacobsohn D, Lalefar N, Farhadfar N, Pulsipher MA, Shenoy S, Petrovic A, Schultz KR, Yanik GA, Blazar BR, Horan JT, Watkins B, Langston A, Qayed M, Kean LS. Higher abatacept exposure after transplant decreases acute GVHD risk without increasing adverse events. Blood. 2023 Aug 24;142(8):700-710. doi: 10.1182/blood.2023020035.

  PMID: 37319437 DERIVED

MeSH Terms

Conditions

Graft vs Host Disease; Neoplasms

Interventions

Abatacept

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Results Point of Contact

• Title: Dr. Leslie Kean
• Organization: Boston Children's Hospital

leslie.kean@childrens.harvard.edu

404-376-0187

Study Officials

• Leslie Kean, MD, PhD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: December 4, 2012
• First Posted: December 6, 2012
• Study Start: February 1, 2013
• Primary Completion: June 30, 2018
• Study Completion: March 30, 2024
• Last Updated: December 11, 2025
• Results First Posted: June 17, 2020

Record last verified: 2025-12

Locations

US (13); CA (1)