Cyclophosphamide, Abatacept, and Tacrolimus for GvHD Prevention

Phase 1

Completed

Conditions: Graft-versus-host Disease

Interventions: Drug: Cyclophosphamide, Abatacept, and Tacrolimus for GvHD Prevention

Registration Number: NCT04503616

Lead Sponsor: NYU Langone Health

Brief Summary: This is a single arm, open label, optimal 2-stage Simon design phase Ib-II clinical trial. Adult patients with hematological malignancies undergoing allogeneic HSCT from first- or second-degree haploidentical donor are eligible for the study if they meet the standard criteria defined in our institutional standard operation procedures (SOPs), meet all inclusion criteria, and do not satisfy any exclusion criteria. Patients will receive non-myeloablative, reduced-intensity or myeloablative conditioning regimen followed by peripheral blood hematopoietic stem cells. Patients will receive cyclophosphamide, abatacept, and short-duration tacrolimus for GvHD prophylaxis.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 46

Inclusion Criteria

Age ≥ 18 years
Karnofsky score ≥ 70%
No evidence of progressive bacterial, viral, or fungal infection
Creatinine clearance > 50 mL/min/1.72m2
Total bilirubin, ALT and 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 HIV serology
Negative pregnancy test: confirmation per negative serum β-human chorionic gonadotropin (β-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 (see Appendix E), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any 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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HSCT Patients	Cyclophosphamide, Abatacept, and Tacrolimus for GvHD Prevention	Adult patients with hematological malignancies undergoing HLA-haploidentical HSCT from first-or second-degree family donors.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Grade II-IV Acute GvHD by Day +120	120 days	The first day of grade II-IV acute GvHD will be used to calculate the cumulative incidence. The cumulative incidence will be defined as the percentage of participants with grade II-IV acute GvHD. The diagnosis of acute GvHD is based on clinical and pathological evaluation by the principal investigator in collaboration with the treating physician. Overall Grades of Acute GvHD: 0 = none; 1. = mild; 2. = moderate; 3. = severe; 4. = life threatening

Secondary Outcome Measures

Name	Time	Method
Cumulative Incidence of Chronic GvHD	Day 365	The first day of chronic GvHD will be used to calculate the cumulative incidence of chronic GvHD. This endpoint will be evaluated through day +365 post-transplant.
Cumulative Incidence of Primary Graft Failure	Day 45	Graft failure is defined as failure to achieve neutrophil engraftment by day +28 or lack of donor chimerism \> 50% by day 45, not due to the underlying malignancy.
Cumulative Incidence of Poor Graft Function	Day 28	Poor Graft Function defined by at least 2 of the following 3 criteria: Hemoglobin \< 8 g/dL, ANC \< 0.5 x 109/L, and platelets \< 20 x 109/L. The cytopenia must be unexplained (such as by disease relapse) and unresponsive to cytokines and must last at least 4 weeks.
Incidence of Secondary Graft Failure	Day 730	Evaluated following engraftment through day +730. Secondary Graft Failure defined as poor graft function associated with donor chimerism \< 5%.
Number of Treatment-Related Deaths	Day 730	Number of participant deaths not attributable to disease relapse or progression. Will be evaluated to day +730.
Relapse Rate	Day 730	Evaluated to day +730 and defined as the percentage of patients in whom the disease for which transplant is performed becomes evident by methods of disease detection after the transplant.
GvHD and Relapse-Free Survival (GRFS)	Day 730	Evaluated to day +730 and defined as the percentage of participants who are without reported grade III-IV acute GvHD, without chronic GvHD requiring systemic therapy, and have not experienced relapse or death.
Overall Survival	Day 730	Evaluated to day +730 and defined as percentage of participants alive at the end of the study's evaluation period.