ABBA CORD: dCBT w/ Abatacept for aGVHD Prophylaxis

NCT06680661 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CASE1924
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to see if adding abatacept to tacrolimus and MMF prevents or reduces the chances of acute graft versus host disease which is a complication that can occur after transplant in participants with blood cancer. The usual therapy for graft versus host disease prevention after a cord blood transplant includes tacrolimus and MMF. The main question this clinical trial aims to answer is whether or not abatacept will be safe and effective in reducing aGVHD rates in dCBT. Participants will:

• Partake in exams, tests, and procedures as part of usual cancer care.
• Partake in conditioning, which is the treatment that is given before a transplant.
• Have a cord blood transplant.
• Partake in radiation following the transplant.

Conditions

Acute Myelogenous Leukemia; Acute Lymphatic Leukemia; Chronic Myelogenous Leukemia; Myelodysplastic Syndromes; Myelodysplastic Syndrome Other; Chronic Myelomonocytic Leukemia; Lymphoma; Hodgkin Lymphoma

Keywords

Chronic Myelomonocytic Lymphoma; Umbilical Cord Blood Transplant; Double Umbilical Cord Transplant; Cord blood

Outcome Measures

Primary Outcomes (1)

• Severe aGVHD free survival

  To assess severe aGVHD (grade III-IV acute GVHD) free survival (SGFS) at T+180.

  180 days after treatment

Secondary Outcomes (23)

• Non-relapse mortality

  1 year post transplant

• Overall Survival

  1 year post transplant

• Rate of relapse

  1 year post transplant

• Disease free survival

  1 year post transplant

• Incidence of chronic GVHD

  1 year post transplant

Study Arms (1)

Cy/Flu/Thio/TBI + dCBT + Tac/MMF + Abatacept

EXPERIMENTAL

Cyclophosphamide (Cy), fludarabine (Flu), thiotepa (Thio), and total body irradiation (TBI) is the preparative regimen for Double Umbilical Cord Transplant (dCBT). Graft-versus-host disease prophylaxis will consist of tacrolimus (Tac) and mycophenolate mofetil (MMF). Abatacept will be administered.

Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Thiotepa; Radiation: Total Body Irradiation; Biological: Double Umbilical Cord Transplant; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Drug: Abatacept

Interventions

Cyclophosphamide DRUG

Cyclophosphamide (Cy) is one part of the conditioning regimen. 50 mg/kg beginning on day -6.

Cy/Flu/Thio/TBI + dCBT + Tac/MMF + Abatacept

Fludarabine DRUG

Fludarabine (Flu) is one part of the conditioning regimen. 150 mg/m2 (30 mg/m2 per day on days -6 to -2)

Cy/Flu/Thio/TBI + dCBT + Tac/MMF + Abatacept

Thiotepa DRUG

Thiotepa (Thio) is one part of the conditioning regimen.10 mg/kg (5 mg/kg per day on days -5 and -4)

Cy/Flu/Thio/TBI + dCBT + Tac/MMF + Abatacept

Total Body Irradiation RADIATION

400 cGy (200 cGy per day on days -2 and -1).

Cy/Flu/Thio/TBI + dCBT + Tac/MMF + Abatacept

Double Umbilical Cord Transplant BIOLOGICAL

Cord blood is a regulated biologic. Selection of cord blood units will be based on published guidelines.

Cy/Flu/Thio/TBI + dCBT + Tac/MMF + Abatacept

Tacrolimus DRUG

Tacrolimus will be administered post transplant. Graft-versus-host disease prophylaxis will consist of tacrolimus and mycophenolate mofetil (MMF), starting on day-5. Tacrolimus will continue at least until day 180 and then be tapered off.

Cy/Flu/Thio/TBI + dCBT + Tac/MMF + Abatacept

Mycophenolate Mofetil DRUG

MMF will be administered post transplant. Graft-versus-host disease prophylaxis will consist of tacrolimus and mycophenolate mofetil (MMF), starting on day-5. MMF will continue until day 30.

Cy/Flu/Thio/TBI + dCBT + Tac/MMF + Abatacept

Abatacept DRUG

Abatacept at a dose of 10mg/kg will be given on days T-1, T+5, T+14 and T+28.

Cy/Flu/Thio/TBI + dCBT + Tac/MMF + Abatacept

Eligibility Criteria

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

You may qualify if:

• Patients with the following hematologic malignancies:
• Acute myelogenous leukemia (AML): High-risk and intermediate-risk AML including:
• Antecedent hematological disease (e.g., myelodysplasia (MDS))
• Treatment-related leukemia
• Complete Remission (CR1) with poor or intermediate-risk cytogenetics or molecular markers (e.g. Flt 3 mutation, 11q23, del 5, del 7, complex cytogenetics)
• CR2 or CR3
• Induction failure or 1st relapse with \< 10% blasts in the marrow
• Acute lymphoblastic leukemia (ALL):
• High-risk CR1 including:
• Poor-risk cytogenetics (e.g., Philadelphia chromosome t(9;22)or 11q23 rearrangements)
• Philadelphia chromosome-like ALL
• Presence of minimal disease by flow cytometry after 2 or more cycles of chemotherapy
• No CR within 4 weeks of initial treatment
• Induction failure with \< 10% blasts in the marrow
• CR2 or CR3

You may not qualify if:

• Patients with inadequate Organ Function as defined by:
• Creatinine clearance \< 50ml/min
• Bilirubin \> 2X institutional upper limit of normal unless Gilbert syndrome
• AST (SGOT) \> 3X institutional upper limit of normal
• ALT (SGPT) \> 3X institutional upper limit of normal
• Pulmonary function: DLCOc \< 60% normal
• Cardiac: left ventricular ejection fraction \< 50
• Patients with uncontrolled inter-current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant or breastfeeding women are excluded from this study because chemotherapy involved with RIC have the significant potential for teratogenic or abortifacient effects.
• Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data.
• Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.
• Presence of donor-specific antibodies against chosen graft source.
• Hematopoietic Cell Transplantation Comorbidity index (HCT-CI) \> 5.
• Prior autologous or allogenic stem cell transplant within the preceding 12 months.

Sponsors & Collaborators

• Leland Metheny: lead

Study Sites (1)

University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic; Lymphoma; Hodgkin Disease

Interventions

Cyclophosphamide; fludarabine; Thiotepa; Whole-Body Irradiation; Tacrolimus; Mycophenolic Acid; Abatacept

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myelodysplastic-Myeloproliferative Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Radiotherapy; Therapeutics; Investigative Techniques; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Study Officials

• Leland Metheny, MD

  University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Leland Metheny, MD

CONTACT

216-844-0139; Leland.Metheny@uhhospitals.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr. Leland Metheny

Model Details: Approximately 20 subjects will be enrolled in this trial: 7 patients will be accrued for the Stage 1. Stage 1 must be complete and the 7th patient reach T+180 prior to enrolling 13 additional patients to Stage 2.

Study Record Dates

• First Submitted: October 31, 2024
• First Posted: November 8, 2024
• Study Start: February 25, 2025
• Primary Completion (Estimated): October 29, 2027
• Study Completion (Estimated): October 31, 2028
• Last Updated: June 4, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Compiled and analyzed patient data will be published upon study completion. Publisher may request Protocol and Statistical Analysis Plan.

Locations

US (1)