Abatacept added to standard drugs to prevent acute graft‑versus‑host disease after double umbilical cord blood transplant
ABBA CORD: Double Umbilical Cord Blood Transplants With Abatacept for Graft Versus Host Disease Prophylaxis
This phase 2 trial will test whether adding abatacept to tacrolimus and MMF can prevent or reduce acute graft‑versus‑host disease in people with blood cancers getting a double umbilical cord blood transplant.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 20 (estimated) |
| Ages | 18 Years to 65 Years |
| Sex | All |
| Sponsor | Case Comprehensive Cancer Center Academic / other |
| Drugs / interventions | chemotherapy, radiation |
| Locations | 1 site (Cleveland, Ohio) |
| Trial ID | NCT06680661 on ClinicalTrials.gov |
What this trial studies
This phase 2 interventional trial adds abatacept to standard GVHD prophylaxis with tacrolimus and mycophenolate mofetil in patients receiving double umbilical cord blood transplants. Participants receive conditioning (cyclophosphamide, fludarabine, thiotepa, and total body irradiation as indicated), the cord blood grafts, and routine post‑transplant exams and testing. The rationale is that double cord blood transplants have high rates of acute GVHD due to HLA disparity, and prior work with abatacept (ABA2) reduced aGVHD in HLA‑mismatched unrelated donor transplants. The study aims to test the safety of abatacept in this setting and see if it lowers rates of grade II–IV and grade III–IV aGVHD compared with historical expectations.
Who should consider this trial
Good fit: Patients with hematologic malignancies who lack an HLA‑matched adult donor and are scheduled to receive a double umbilical cord blood transplant with the specified conditioning regimen are the intended candidates.
Not a fit: Patients who will receive an HLA‑matched adult donor transplant, are not receiving a double cord blood graft, or have contraindications to abatacept or uncontrolled active infections are unlikely to benefit from this approach.
Why it matters
Potential benefit: If successful, adding abatacept could substantially reduce severe acute GVHD after double cord blood transplant, lowering complications and transplant‑related morbidity and mortality.
How similar studies have performed: A prior ABA2 study showed abatacept reduced aGVHD in HLA‑mismatched unrelated donor transplants, but abatacept has not been widely tested specifically in double cord blood transplants.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
* 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
* Myelodysplastic syndromes (MDS), Intermediate, High or Very High Risk by the revised international prognostic scoring system or treatment related MDS.
* Bi-phenotypic or mixed-phenotypic acute leukemia in:
* CR.
* Induction failure or 1st relapse with \< 10% blasts in the marrow.
* Chronic Myelogenous Leukemia (CML) in second chronic phase after accelerated or blast crisis.
* Chronic Myelomonocytic Leukemia (CMML)
* Hodgkin's Lymphoma that is relapsed or refractory
* Age \> or equal to 18 years, \< or equal to 70yrs
* KPS \> or equal to 80 for Flu/Cy/Thio/TBI; KPS \> 60 for Flu/Treo/TBI
* Patients without a suitable HLA-matched related or unrelated donor
* Patient with the following CB units:
* At least two 4-8/8 HLA high resolution matched CB units. Both must have a cell dose of 1.5x107 TNC/kg each and 1.5x105 CD34+/kg
* A minimum of 1 CB unit as back up.
* Concurrent Therapy for Extramedullary Leukemia or CNS Lymphoma: Concurrent therapy or prophylaxis for testicular leukemia, CNS leukemia, and CNS lymphoma including standard intrathecal chemotherapy and/or radiation therapy will be allowed as clinically indicated. Such treatment may continue until the planned course is completed. Subjects must be in CNS remission at the time of protocol enrollment if there is a history of CNS involvement. Maintenance therapy after transplant is allowed.
* Subjects must have the ability to understand and the willingness to sign a written informed consent document.
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of \< 1% per year during the treatment period and for 12 months after the last dose of abatacept.
* A woman is considered to be of childbearing potential if she is \< 60 years old, postmenarcheal, has not reached a postmenopausal state (\< 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
* Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
* For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures with female partners of reproductive potential, and agreement to refrain from donating sperm, as defined below:
* With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of \< 1% per year during the treatment period and for 12 months after the last dose of abatacept. Men must refrain from donating sperm during this same period. With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 12 months after the last dose of abatacept.
* The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
Exclusion Criteria:
* 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.
Where this trial is running
Cleveland, Ohio
- University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center — Cleveland, Ohio, United States (Recruiting)
Study contacts
- Principal investigator: Leland Metheny, MD — University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
- Study coordinator: Leland Metheny, MD
- Email: Leland.Metheny@uhhospitals.org
- Phone: 216-844-0139
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.