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Cyclophosphamide, Abatacept, and Tacrolimus for the Prevention of GvHD

Primary Purpose

Graft Vs Host Disease

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cyclophosphamide
Abatacept
Tacrolimus
Sponsored by
NYU Langone Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Graft Vs Host Disease focused on measuring Haploidentical Hematopoietic Stem Cell Transplantation

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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, Alanine Aminotransferase and Aspartate Aminotransferase < 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

Sites / Locations

  • NYU Langone HealthRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Reduced-Dose Post-Transplant Cyclophosphamide, Abatacept, and Short-Duration Tacrolimus

Arm Description

Participants to receive: Cyclophosphamide 25 mg/kg IV over 1 hour on Day 3 and Day 4 following transplant Abatacept 10 mg/kg IV on Day 5, Day 14, Day 28, and Day 56 following transplant Tacrolimus 0.02 mg/kg IV by continuous infusion, starting on Day 5 following transplant. May switch to oral administration when tolerated, adjusted to maintain a drug level between 5-12ng/mL. Tacrolimus treatment is continued until Day 60 and then tapered over a period of 4 weeks in the absence of GvHD.

Outcomes

Primary Outcome Measures

Cumulative Incidence of Grades II-IV Acute GvHD
The first day of acute GvHD of any grade is used to calculate the cumulative incidence for that grade. The diagnosis of acute GvHD is based on clinical and pathological evaluation by the principal investigator in collaboration with the treating physician.

Secondary Outcome Measures

Cumulative Incidence of Chronic GvHD
The first day of chronic GvHD is used to calculate the cumulative incidence of chronic GvHD. The diagnosis of chronic GvHD is based on clinical and pathological evaluation by the principal investigator in collaboration with the treating physician.
Number of Participants Presenting with Primary Graft Failure
Primary graft failure is defined as failure to achieve neutrophil engraftment by Day 28 after transplant or lack of donor chimerism greater than 50% by Day 45, not due to the underlying malignancy.
Number of Participants Presenting with Poor Graft Function
Poor graft function is defined by at least 2 of the following 3 criteria: Hemoglobin less than 8 g/dL, absolute neutrophil count less than 0.5 x 109/L, and platelets less than 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.
Number of Participants Presenting with Secondary Graft Failure
Secondary graft failure is defined as poor graft function associated with donor chimerism less than 5%.
Treatment-Related Mortality (TRM) Rate
The proportion of participant deaths not attributable to disease relapse or progression.
Relapse Rate (RR)
The proportion of participants in whom the disease for which transplant was performed is evident by methods of disease detection.
GvHD and Relapse-Free Survival (GRFS) Rate
The proportion of participants who are without reported grade III-IV acute GvHD, chronic GvHD requiring systemic therapy and have not experienced relapse or death.
Overall Survival (OS) Rate
The proportion of participants who are alive at the end of the study's evaluation period.

Full Information

First Posted
November 10, 2022
Last Updated
October 3, 2023
Sponsor
NYU Langone Health
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1. Study Identification

Unique Protocol Identification Number
NCT05621759
Brief Title
Cyclophosphamide, Abatacept, and Tacrolimus for the Prevention of GvHD
Official Title
Phase II Single-Arm Open-Label Study Of Reduced-Dose Post-Transplant Cyclophosphamide, Abatacept, and Short-Duration Tacrolimus for the Prevention of Graft-Versus-Host Disease (GVHD) Following Haploidentical Hematopoietic Stem Cell Transplantation (HSCT)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 23, 2022 (Actual)
Primary Completion Date
August 23, 2024 (Anticipated)
Study Completion Date
August 23, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NYU Langone Health

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a single arm, open label, phase 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 dosed reduced cyclophosphamide, abatacept, and short-duration tacrolimus for GvHD prophylaxis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft Vs Host Disease
Keywords
Haploidentical Hematopoietic Stem Cell Transplantation

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
92 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Reduced-Dose Post-Transplant Cyclophosphamide, Abatacept, and Short-Duration Tacrolimus
Arm Type
Experimental
Arm Description
Participants to receive: Cyclophosphamide 25 mg/kg IV over 1 hour on Day 3 and Day 4 following transplant Abatacept 10 mg/kg IV on Day 5, Day 14, Day 28, and Day 56 following transplant Tacrolimus 0.02 mg/kg IV by continuous infusion, starting on Day 5 following transplant. May switch to oral administration when tolerated, adjusted to maintain a drug level between 5-12ng/mL. Tacrolimus treatment is continued until Day 60 and then tapered over a period of 4 weeks in the absence of GvHD.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
Nitrogen mustard alkylating agent produced by Bristol-Myers Squibb.
Intervention Type
Drug
Intervention Name(s)
Abatacept
Other Intervention Name(s)
Prograf
Intervention Description
Calcineurin-inhibitor produced by Astellas.
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Other Intervention Name(s)
Orencia
Intervention Description
Selective T cell co-stimulation modulator produced by Bristol-Myers Squibb.
Primary Outcome Measure Information:
Title
Cumulative Incidence of Grades II-IV Acute GvHD
Description
The first day of acute GvHD of any grade is used to calculate the cumulative incidence for that grade. The diagnosis of acute GvHD is based on clinical and pathological evaluation by the principal investigator in collaboration with the treating physician.
Time Frame
Up to Day 120
Secondary Outcome Measure Information:
Title
Cumulative Incidence of Chronic GvHD
Description
The first day of chronic GvHD is used to calculate the cumulative incidence of chronic GvHD. The diagnosis of chronic GvHD is based on clinical and pathological evaluation by the principal investigator in collaboration with the treating physician.
Time Frame
Up to Day 365
Title
Number of Participants Presenting with Primary Graft Failure
Description
Primary graft failure is defined as failure to achieve neutrophil engraftment by Day 28 after transplant or lack of donor chimerism greater than 50% by Day 45, not due to the underlying malignancy.
Time Frame
Up to Day 45
Title
Number of Participants Presenting with Poor Graft Function
Description
Poor graft function is defined by at least 2 of the following 3 criteria: Hemoglobin less than 8 g/dL, absolute neutrophil count less than 0.5 x 109/L, and platelets less than 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.
Time Frame
Up to Day 30
Title
Number of Participants Presenting with Secondary Graft Failure
Description
Secondary graft failure is defined as poor graft function associated with donor chimerism less than 5%.
Time Frame
Up to Day 730
Title
Treatment-Related Mortality (TRM) Rate
Description
The proportion of participant deaths not attributable to disease relapse or progression.
Time Frame
Up to Day 730
Title
Relapse Rate (RR)
Description
The proportion of participants in whom the disease for which transplant was performed is evident by methods of disease detection.
Time Frame
Up to Day 730
Title
GvHD and Relapse-Free Survival (GRFS) Rate
Description
The proportion of participants who are without reported grade III-IV acute GvHD, chronic GvHD requiring systemic therapy and have not experienced relapse or death.
Time Frame
Up to Day 730
Title
Overall Survival (OS) Rate
Description
The proportion of participants who are alive at the end of the study's evaluation period.
Time Frame
Up to Day 730

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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, Alanine Aminotransferase and Aspartate Aminotransferase < 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Emma Futamura
Phone
212-731-6217
Email
Emma.Futamura@nyulangone.org
First Name & Middle Initial & Last Name or Official Title & Degree
Kiselle Mangalindan
Phone
347-429-0296
Email
KiselleAnne.Mangalindan@nyulangone.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jaime Suarez Londono
Organizational Affiliation
NYU Langone Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Only available to study team members.

Learn more about this trial

Cyclophosphamide, Abatacept, and Tacrolimus for the Prevention of GvHD

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