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

Phase 1
Active, not recruiting
Conditions
Interventions
Registration Number
NCT05289167
Lead Sponsor
NYU Langone Health
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 exclusi...

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 mat...

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
74
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.
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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Participants with hematological malignanciesAbataceptParticipants 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.
Participants with hematological malignanciesCyclophosphamideParticipants 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.
Participants with hematological malignanciesBortezomibParticipants 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.
Primary Outcome Measures
NameTimeMethod
Phase I:Incidence Dose limiting toxicity (DLT)Day+1 to Day +120

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 GvHDDay+1 to Day +120

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
NameTimeMethod
Poor graft functionDay +1 to Day +30

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 failureDay +1

Evaluated after engraftment is achieved will be calculated from date of engraftment for all subjects with engraftment

Relapse rate (RR)Day +1 to Day +730

Evaluated to day +730 and will be analyzed for all subjects who received a transplant and for all transplanted subjects that completed treatment

Primary graft failureDay +1 to Day +30

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

Treatment-related mortality (TRM)Day +1 to Day +730

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.

Chronic GvHDDay +1 to Day +365

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

GvHD and relapse-free survival (GRFS)Day +1 to Day +730

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)Day +1 to Day +730

Evaluated to day +730 and considers all participants who received a transplant and for all transplanted subjects who completed prophylactic treatment

Trial Locations

Locations (1)

NYU Langone Health

🇺🇸

New York, New York, United States

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