Back to resultsHigh-Dose Post-Transplant Cyclophosphamide, Bortezomib and Abatacept for the Prevention of Graft-versus-Host-Disease (GvHD) Following Allogenic Hematopoietic Stem Cell Transplantation (HSCT) Study
Primary Purpose
Graft-versus-host Disease
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Cyclophosphamide
Abatacept
Bortezomib
Sponsored by
About this trial
This is an interventional treatment trial for Graft-versus-host Disease
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
- ALT and AST <3 x the upper limit of normal
- Total bilirubin <2 x the upper limit of normal (except for Gilbert's syndrome)
- Alkaline phosphatase ≤250 IU/L
- Left Ventricular Ejection Fraction (LVEF) >45%
- Adjusted Carbon Monoxide Diffusing Capacity (DLCO) >50%
- Negative HIV serology
- Negative pregnancy test: Confirmation per negative serum β-human chorionic gonadotropin (β-hCG)
- Willing to comply with all study procedures and be available for the duration of the study.
Exclusion Criteria:
- Pregnant or nursing females or women of reproductive capability who are unwilling to completely abstain from heterosexual sex or practice 2 effective methods of contraception from start of conditioning through 90 days after the last dose of study drug. 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 from the start of conditioning 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 D), 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.
- Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma, an in-situ malignancy, or low-risk prostate cancer after curative therapy.
- 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
- Pregnant women
Sites / Locations
- NYU Langone HealthRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Participants with hematological malignancies
Arm Description
Participants undergoing Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) will receive a combination of cyclophosphamide, known commercially as Cytoxan®, abatacept, known as Orecia® and bortezomib commercially known as Velcade®, to reduce the rate of graft-versus-host disease (GvHD). These medications will be given for GvHD prevention during the transplant process.
Outcomes
Primary Outcome Measures
Phase I:Incidence Dose limiting toxicity (DLT)
Defined as grade 4 non-hematologic toxicity affecting the oral cavity, gastrointestinal tract, lung, heart, liver, kidney, bladder, or central nervous system.
Phase II: Grades II-IV Acute GvHD
The first day of grades II-IV acute GvHD will be recorded for that grade. This end point will be evaluated through day +120 post-transplant.
Secondary Outcome Measures
Chronic GvHD
The diagnosis of chronic GvHD is based on clinical and pathological evaluation by the principal investigator in collaboration with the treating physician.The analysis will be based on the maximum grade of chronic GvHD
Primary graft failure
Incidence of graft failure will be calculated from date of transplant to failure for all subjects who receive a transplant and any prophylactic treatment and from date of completion of prophylactic treatment for all participants that completed treatment
Poor graft function
Incidence of poor graft function will be calculated, from date of transplant to failure for all subjects who receive a transplant and any prophylactic treatment and from date of completion of prophylactic treatment for all participants that completed treatment
Secondary graft failure
Evaluated after engraftment is achieved will be calculated from date of engraftment for all subjects with engraftment
Treatment-related mortality (TRM)
Analyzed based on participants that who received a transplant with any prophylactic treatment and for all subjects who received a transplant and completed prophylactic treatment.
Relapse rate (RR)
Evaluated to day +730 and will be analyzed for all subjects who received a transplant and for all transplanted subjects that completed treatment
GvHD and relapse-free survival (GRFS)
Evaluated to day +730 and considers as successes participants that are without reported GvHD III-IV acute GvHD, chronic GvHD requiring systemic therapy and have not experienced relapse or death after transplant
Overall survival (OS)
Evaluated to day +730 and considers all participants who received a transplant and for all transplanted subjects who completed prophylactic treatment
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05289167
Brief Title
High-Dose Post-Transplant Cyclophosphamide, Bortezomib and Abatacept for the Prevention of Graft-versus-Host-Disease (GvHD) Following Allogenic Hematopoietic Stem Cell Transplantation (HSCT) Study
Official Title
A Phase I-II Study of High-Dose Post-Transplant Cyclophosphamide, Bortezomib and Abatacept for the Prevention of Graft-versus-Host-Disease (GvHD) Following Allogenic Hematopoietic Stem Cell Transplantation (HSCT)
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 13, 2022 (Actual)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
March 2024 (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.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a phase I-II clinical trial. Adult subjects with hematological malignancies undergoing allogeneic HSCT from an HLA matched sibling or ≥7 out of 8 allele level HLA matched unrelated donor are eligible for the study if they meet the criteria defined in our standard operation procedures (SOPs), meet all inclusion criteria, and do not satisfy any exclusion criteria. Subjects will receive a standard of care conditioning regimen. Subjects will receive investigational PTCy, investigational bortezomib and investigational abatacept as GvHD prophylaxis.
Detailed Description
The study will have a phase I and phase II potions. The phase I portion will employ a 3+3 dose escalation design to define the maximum tolerated dose (MTD) of abatacept added to PTCy and bortezomib following HSCT. The phase II portion will consist of two single arm, open label, optimal 2-stage Simon design studies conducted in two separate strata for HLA matched and HLA mismatched donor transplants. Adult patients with hematological malignancies undergoing allogeneic HSCT from an HLA matched sibling or ≥7 out of 8 allele level HLA matched unrelated 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. Subjects will receive a standard of care conditioning regimen followed by peripheral blood hematopoietic stem cells. Subjects with unrelated donors will also receive rabbit anti-thymocyte globulin (rATG). Subjects will receive investigational PTCy, investigational bortezomib and investigational abatacept as GvHD prophylaxis. The phase II portion dose of abatacept will be the MTD as determined in the phase I portion of the study. In the phase II portions, subjects will be stratified based on whether they receive a matched sibling or matched unrelated (matched) donor transplant and ≥7 out of 8, allele level matched (mismatched) unrelated donor transplant.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft-versus-host Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
74 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Participants with hematological malignancies
Arm Type
Experimental
Arm Description
Participants undergoing Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) will receive a combination of cyclophosphamide, known commercially as Cytoxan®, abatacept, known as Orecia® and bortezomib commercially known as Velcade®, to reduce the rate of graft-versus-host disease (GvHD). These medications will be given for GvHD prevention during the transplant process.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan®
Intervention Description
50 mg/kg IV over 1 hour on Day +3 and +4
Intervention Type
Drug
Intervention Name(s)
Abatacept
Other Intervention Name(s)
Orecia®
Intervention Description
Dose level 0: 10 mg/kg IV over 30 minutes on day +5
Dose level 1: 10mg/kg IV over 30 minutes on day +5 and +14
Dose level 2: 10mg/kg IV over 30 minutes on day +5, +14, and +28
Intervention Type
Drug
Intervention Name(s)
Bortezomib
Other Intervention Name(s)
Velcade®
Intervention Description
1.3 mg/m2 IV 6 hours after graft infusion completion and 72 hours thereafter.
Primary Outcome Measure Information:
Title
Phase I:Incidence Dose limiting toxicity (DLT)
Description
Defined as grade 4 non-hematologic toxicity affecting the oral cavity, gastrointestinal tract, lung, heart, liver, kidney, bladder, or central nervous system.
Time Frame
Day+1 to Day +120
Title
Phase II: Grades II-IV Acute GvHD
Description
The first day of grades II-IV acute GvHD will be recorded for that grade. This end point will be evaluated through day +120 post-transplant.
Time Frame
Day+1 to Day +120
Secondary Outcome Measure Information:
Title
Chronic GvHD
Description
The diagnosis of chronic GvHD is based on clinical and pathological evaluation by the principal investigator in collaboration with the treating physician.The analysis will be based on the maximum grade of chronic GvHD
Time Frame
Day +1 to Day +365
Title
Primary graft failure
Description
Incidence of graft failure will be calculated from date of transplant to failure for all subjects who receive a transplant and any prophylactic treatment and from date of completion of prophylactic treatment for all participants that completed treatment
Time Frame
Day +1 to Day +30
Title
Poor graft function
Description
Incidence of poor graft function will be calculated, from date of transplant to failure for all subjects who receive a transplant and any prophylactic treatment and from date of completion of prophylactic treatment for all participants that completed treatment
Time Frame
Day +1 to Day +30
Title
Secondary graft failure
Description
Evaluated after engraftment is achieved will be calculated from date of engraftment for all subjects with engraftment
Time Frame
Day +1
Title
Treatment-related mortality (TRM)
Description
Analyzed based on participants that who received a transplant with any prophylactic treatment and for all subjects who received a transplant and completed prophylactic treatment.
Time Frame
Day +1 to Day +730
Title
Relapse rate (RR)
Description
Evaluated to day +730 and will be analyzed for all subjects who received a transplant and for all transplanted subjects that completed treatment
Time Frame
Day +1 to Day +730
Title
GvHD and relapse-free survival (GRFS)
Description
Evaluated to day +730 and considers as successes participants that are without reported GvHD III-IV acute GvHD, chronic GvHD requiring systemic therapy and have not experienced relapse or death after transplant
Time Frame
Day +1 to Day +730
Title
Overall survival (OS)
Description
Evaluated to day +730 and considers all participants who received a transplant and for all transplanted subjects who completed prophylactic treatment
Time Frame
Day +1 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
ALT and AST <3 x the upper limit of normal
Total bilirubin <2 x the upper limit of normal (except for Gilbert's syndrome)
Alkaline phosphatase ≤250 IU/L
Left Ventricular Ejection Fraction (LVEF) >45%
Adjusted Carbon Monoxide Diffusing Capacity (DLCO) >50%
Negative HIV serology
Negative pregnancy test: Confirmation per negative serum β-human chorionic gonadotropin (β-hCG)
Willing to comply with all study procedures and be available for the duration of the study.
Exclusion Criteria:
Pregnant or nursing females or women of reproductive capability who are unwilling to completely abstain from heterosexual sex or practice 2 effective methods of contraception from start of conditioning through 90 days after the last dose of study drug. 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 from the start of conditioning 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 D), 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.
Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma, an in-situ malignancy, or low-risk prostate cancer after curative therapy.
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
Pregnant women
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kelsey Stocker
Phone
646-501-4723
Email
kelsey.stocker@nyulangone.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ahmad Al-Homsi, MD
Organizational Affiliation
NYU Langone Health
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
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kelsey Stocker
Phone
646-501-4723
Email
kelsey.stocker@nyulangone.org
First Name & Middle Initial & Last Name & Degree
Ahmad Al-Homsi, MD
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Information only to approved study team
Learn more about this trial
High-Dose Post-Transplant Cyclophosphamide, Bortezomib and Abatacept for the Prevention of Graft-versus-Host-Disease (GvHD) Following Allogenic Hematopoietic Stem Cell Transplantation (HSCT) Study
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