Comparing Cyclophosphamide and Abatacept With Standard of Care Treatment Following Stem Cell Transplantation

NCT03680092 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 180383
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate whether the combination of cyclophosphamide and abatacept versus the treatment used in standard of care will reduce the incidence of moderate and severe chronic graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation. GVHD occurs when the cells from your donor (the graft) see your body's cells (the host) as different and attack them.

Conditions

GVHD; Hematologic Neoplasms

Keywords

cancer; Graft-Versus-Host Disease; Hematologic Neoplasms; Abatacept; Cyclophosphamide; GVHD prophylaxis; stem cell transplantation; High risk hematologic malignancy; hematologic malignancy; Allogeneic Hematopoetic Stem Cell Transplantation; GVHD

Outcome Measures

Primary Outcomes (1)

• Occurrence of Moderate and Severe Chronic GVHD at One Year Post Transplant

  The occurrence of moderate and severe chronic GVHD at one year post Chronic GVHD will be diagnosed and staged according to the previously published and widely accepted National Institutes of Health consensus criteria

  through study completion, an average of 1 year

Secondary Outcomes (1)

• GVHD- and Relapse- Free Survival by One Year Post Transplant

  through study completion, an average of 1 year

Study Arms (2)

Cyclophosphamide and abatacept

EXPERIMENTAL

The GVHD prophylaxis regimen on the experimental arm will consist of high dose Cyclophosphamide on Days +3 and +4 followed by abatacept for 6 months. Abatacept at a dose of 10mg/kg will be administered on days +5, +14 and +28, +56, +84, +112, +140, +168

Drug: Cyclophosphamide; Drug: abatacept

methotrexate and tacrolimus

ACTIVE COMPARATOR

The GVHD prophylaxis regimen on the standard of care arm will consist of methotrexate on Days +1,+3, +6 and +11 and tacrolimus

Drug: Methotrexate; Drug: Tacrolimus

Interventions

Cyclophosphamide DRUG

Day 3 and day 4 following transplant. Dosing will be based on patients' actual weight up to 120% of ideal body weight, above which it will be based on adjusted ideal body weight (ideal weight plus 50% of the difference between ideal and actual weight).

Also known as: cytophosphane, Cytoxan, Neosar

Cyclophosphamide and abatacept

abatacept DRUG

Abatacept at a dose of 10mg/kg will be administered on days +5, +14 and +28, +56, +84, +112, +140, +168

Also known as: ORENCIA

Cyclophosphamide and abatacept

Methotrexate DRUG

standard of care Methotrexate 5 mg/m2 on Days 1, 3, 6 and 11

Also known as: Trexall

methotrexate and tacrolimus

Tacrolimus DRUG

Tacrolimus per institutional guidelines

Also known as: Prograf, Astagraf XL, Envarsus XR

methotrexate and tacrolimus

Eligibility Criteria

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

You may qualify if:

• High risk hematologic malignancy justifying the need for an allogeneic hematopoetic stem cell transplantation: AML, ALL, CML in accelerated or blast phase, MDS/MPN, NHL, Hodgkin lymphoma, and multiple myeloma
• Creatinine clearance \> 40
• Adequate hepatic function
• Normal cardiac function (EF \> 50%)

You may not qualify if:

• Patients with hematologic malignancies for which transplant is not the only curative option, such as AML with good or intermediate cytogenetics or molecular markers in CR1 or CML in chronic phase
• Inability to identify an 10/10 HLA-Matched Donor (related or unrelated) or a haploidentical donor
• Active malignant disease relapse
• Active, uncontrolled infection, uncontrolled cardiac angina, symptomatic congestive heart failure
• Life expectancy \<3 months
• Pregnancy or lactation
• Patients may not be receiving any other investigational agents in the last 28 days
• Patients with chronic myeloid leukemia in first chronic phase

Sponsors & Collaborators

• Dimitrios Tzachanis, MD PhD: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Related Publications (1)

• Koura D, Dykes K, Goodman A, Costello C, Mulroney C, Mangan JK, Tanaka TN, Ball ED, Hamdan A, Jeong AR, Mirocha J, Zhang Q, Ogrodnik P, McConnell K, Maroge JJ, Padilla M, Morris GP, Tzachanis D. A prospective clinical trial of GVHD prophylaxis with posttransplant cyclophosphamide and abatacept. Blood Adv. 2025 Aug 26;9(16):4336-4344. doi: 10.1182/bloodadvances.2024015094.

  PMID: 40554429 DERIVED

MeSH Terms

Conditions

Hematologic Neoplasms; Neoplasms; Graft vs Host Disease

Interventions

Cyclophosphamide; Abatacept; Methotrexate; Tacrolimus

Condition Hierarchy (Ancestors)

Neoplasms by Site; Hematologic Diseases; Hemic and Lymphatic Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Macrolides; Lactones

Results Point of Contact

• Title: Dr. Dimitrios Tzachanis
• Organization: University of California, San Diego

dtzachanis@health.ucsd.edu

(858) 822-6600

Study Officials

• Dimitrios Tzachanis, MD PhD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

• Divya Koura, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Clinical Professor of Medicine

Study Record Dates

• First Submitted: September 19, 2018
• First Posted: September 21, 2018
• Study Start: November 26, 2019
• Primary Completion: June 15, 2023
• Study Completion: June 15, 2023
• Last Updated: October 2, 2025
• Results First Posted: October 2, 2024

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)