Skip to main content

High-Dose Cyclophosphamide, Abatacept, and Tacrolimus for the Prevention of Graft Versus Host Disease following Donor Stem Cell Transplantation in Patients with Hematologic Cancers

Trial Status: Active

This phase Ib / II trial investigates the effect of combination therapy with high-dose cyclophosphamide, abatacept, and tacrolimus to prevent the occurrence of graft versus host disease (GvHD) after donor stem cell transplantation in patients with hematologic (blood) cancers. GvHD is a condition that occurs when donated stem cells or bone marrow (the graft) see the healthy tissues in the patient’s body (the host) as foreign and attack them. T cells play a key role in the development of GvHD. Cyclophosphamide, abatacept and tacrolimus may be effective in preventing GvHD development by inhibiting the growth, replication or activity of T cells.

Inclusion Criteria

  • Patients with hematological malignancies undergoing an allogeneic transplant with a conditioning regimen, using an eligible human leukocyte antigen (HLA)-haploidentical related donor
  • Karnofsky score >= 70%
  • No evidence of progressive bacterial, viral, or fungal infection
  • Creatinine clearance > 50 mL/min/1.72 m^2
  • Total bilirubin < 2 x the upper limit of normal (except for diagnosed Gilbert’s syndrome)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2 x the upper limit of normal (except for diagnosed Gilbert’s syndrome)
  • Alkaline phosphatase =< 250 IU/L
  • Left ventricular ejection fraction (LVEF) > 45%
  • Adjusted carbon monoxide diffusing capacity (DLCO) > 60%
  • Negative human immunodeficiency virus (HIV) serology
  • Negative pregnancy test: confirmation per negative serum beta-human chorionic gonadotropin (B-hCG) for women of childbearing age and potential

Exclusion Criteria

  • Donors are excluded in case of donor-specific HLA antibodies or positive cross-match
  • Pregnant or nursing females or women of child bearing age or potential, who are unwilling to completely abstain from heterosexual sex or practice 2 effective methods of contraception from the first dose of conditioning regimen through day +180. A woman of reproductive capability is one who has not undergone a hysterectomy (removal of the womb), has not had both ovaries removed, or has not been post-menopausal (stopped menstrual periods) for more than 24 months in a row
  • Male subjects who refuse to practice effective barrier contraception during the entire study treatment period and through a minimum of 90 days after the last dose of study drug, or completely abstain from heterosexual intercourse. This must be done even if they are surgically sterilized (i.e., post-vasectomy)
  • Inability to provide informed consent
  • Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
  • Known allergies to any of the components of the investigational treatment regimen
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study
  • Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial
  • Prisoners

New York

New York
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Status: ACTIVE
Contact: Ahmad Samer Al-Homsi
Phone: 646-501-4848

PRIMARY OBJECTIVE:

I. Estimate the incidence of grades II-IV acute GvHD in patients receiving cyclophosphamide, abatacept, and tacrolimus as GvHD prophylaxis.

SECONDARY OBJECTIVES:

I. Estimate the incidence of the following: chronic GvHD, primary graft failure, poor graft function, and secondary graft failure, treatment-related mortality (TRM), relapse rate (RR), GvHD and relapse free survival (GRFS), overall survival (OS).

II. Assess immune reconstitution by quantifying CD3+, CD4+, CD8+, and CD19+ in comparison to established reference data.

OUTLINE:

CONDITIONING: Patients receive a standard of care myeloablative, reduced-intensity, or nonmyeloablative conditioning regimen between days -6 and -1 per the treating physician.

TRANSPLANT: Patients receive peripheral blood CD34+ cells via infusion on day 0.

GVHD PROPHYLAXIS: Patients receive cyclophosphamide intravenously (IV) over 1 hour on days 3 and 4, abatacept IV over 30 minutes on days 5, 14, and 28, and tacrolimus IV continuously starting on day 5. Patients may receive tacrolimus orally (PO) twice daily (BID) when they are able to. Treatment with tacrolimus continues for up to day 60, then tapered over a period of 4 weeks in the absence of GvHD.

After completion of study, patients are followed up weekly until day 100, monthly until day 180, then every 3 months until day 730.

Trial Phase Phase I/II

Trial Type Prevention

Lead Organization
Laura and Isaac Perlmutter Cancer Center at NYU Langone

Principal Investigator
Ahmad Samer Al-Homsi

  • Primary ID s20-00136
  • Secondary IDs NCI-2020-05582
  • Clinicaltrials.gov ID NCT04503616