Recruiting
Phase 2

Abatacept & Tacrolimus

Sponsor:

Leland Metheny

Code:

NCT06680661

Conditions

Acute Myelogenous Leukemia

Acute Lymphatic Leukemia

Chronic Myelogenous Leukemia

Myelodysplastic Syndromes

Myelodysplastic Syndrome Other

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Interventions

Cyclophosphamide

Fludarabine

Thiotepa

Total Body Irradiation

Double Umbilical Cord Transplant

Study Details

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

Study ID

NCT06680661

Start date

Feb 25, 2025

Status verified date

Jun, 2025

Completion date

Oct 31, 2028

Anticipated

Primary completion date

Oct 29, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

20 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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

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.

Interventions

Cyclophosphamide

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

Fludarabine

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

Thiotepa

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

Total Body Irradiation

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

Double Umbilical Cord Transplant

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

Tacrolimus

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.

Mycophenolate Mofetil

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.

Abatacept

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

Primary outcome measure

  • Severe aGVHD free survival [ Time Frame: 180 days after treatment ]

Central Contacts and Locations

Central contacts

Leland Metheny, MD

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

Locations

University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Recruiting

Cleveland, Ohio, United States, 44106

Contacts

Leland Metheny, MD

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

More Information

Sponsor

Leland Metheny

Last update posted

Jun 4, 2025

Last verified

Jun, 2025

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Leland Metheny on 2025-06-04.