Back to resultsPost-Transplant Cyclophosphamide in Patients Aged >/= 70 Years Undergoing Haploidentical Transplant (GeriBMT)
Primary Purpose
Hematologic Malignancies
Status
Not yet recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Cyclophosphamide
Sponsored by
About this trial
This is an interventional treatment trial for Hematologic Malignancies focused on measuring Allogeneic Transplantation
Eligibility Criteria
Inclusion Criteria: Patient age >/= 70 years Patient has a related donor who is a human leukocyte antigens (HLA) haploidentical match Patient and Donor sign the Informed Consent Form for the study Patient meets standard criteria for allogeneic stem cell transplant Patient is deemed suitable to receive Flu/TBI 800 conditioning regimen as standard of care transplant Donor is willing to donate peripheral blood stem cells (PBSC) Exclusion Criteria: Patient has a diagnosis of myelofibrosis Patient has high titer antibodies (>10,000 mean fluorescent intensity) against one or more donor HLA antigens Patient has undergone prior autologous or allogeneic stem cell transplant Inability to collect at least 3 x 10^6 CD34+ PBSCs/kg recipient weight from the donor Requiring sedation for cardiac MRIs. Prohibited Implants and/or Devices: Mechanical, magnetic or electrical activated implants (i.e. cardiac pacemakers, neurostimulators and infusion pumps) Ferromagnetic implants and ferromagnetic foreign bodies, such as intracranial, aneurysm clips, shrapnel and intraocular metal chips as these could become dislodged. Subjects with claustrophobia, problems being in enclosed spaces, or inability to lie supine.
Sites / Locations
- Cedars-Sinai Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Open Arm
Arm Description
All patients will receive cyclophosphamide on Day +3 and Day +4 following transplant.
Outcomes
Primary Outcome Measures
Maximum grade acute GVHD by day +100 by Modified Keystone Criteria
Evaluate the frequency of grade III/IV acute GVHD using Modified Keystone Criteria
Secondary Outcome Measures
Time to neutrophil and platelet engraftment
Days to neutrophil and platelet engraftment since transplant
Non-Relapse mortality
Rate of treatment-related mortality
Chronic Graft Versus Host Disease (GVHD) at 1 year
Rate and severity of patients with chronic GVHD at day 365 post-transplantation.
Chronic GVHD is when the donated stem cells attack the body after 100 days post-transplant. Chronic GVHD is defined by NIH Consensus Criteria for chronic GVHD.
Relapse
Percentage of patients who relapse by year 1
Overall Survival (OS)
Overall survival at 1 year
Graft Versus Host Disease (GVHD)-free and Relapse Free Survival
Percentage of patients without relapse or GVHD at 1 year
Change in cardiac function
Change in cardiac (heart) injury defined by any of an increase in T1 time > 500 ms from pre-transplant imaging, T2 time > 5 ms from pre-transplant imaging, or a decrease in left ventricular ejection fraction > 10% of the original measurement to below 53% from post-transplant imaging.
Change in active daily living
Change in function over time as determined by Lawton Activities of Daily Living questionnaire.
- Patients will choose either 0 or 1 to rate their level of function with 1 being the highest level of function.
Change in function
Change in function over time as determined by the Patient-Reported Outcomes Measurement Information System (PROMIS) Cancer Function Brief 3-Dimensional Profile.
- Patients will rate their physical condition and fatigue using an inverse 5-item likert scale where 5 represents the highest level of function or the greatest amount of impact on function.
Change in pain
Change in pain over time as determined by the Patient-Reported Outcomes Measurement Information System (PROMIS) Cancer Function Brief 3-Dimensional Profile.
- Patients will rate their level of pain using a scale from 0 to 10 with 10 being the highest level of pain.
Change in physical function
Change in lower limb functioning over time as evaluated by the Short Physical performance Battery. (SPPB).
- Patients will complete a series of tests evaluating balance, speed and standing capabilities. Patients will be rated using a scale of 0 to 12 where a score of less than 10 indicates mobility limitations.
Change in grip strength
Change in grip strength as measured using the Jamar dynamometer (device used to measure grip)
Change in cognitive function
Change in cognitive function over time using the Patient-Reported Outcomes Measurement Information System (PROMIS) Cognition questionnaire.
-Patients will rate their cognitive ability on a scale of 1 to 5 with 5 representing the least amount of difficulty.
Change in mental health
Change in mental health over time using the Patient-Reported Outcomes Measurement Information System (PROMIS) 29 Depression Questionnaire.
- Patients will rate their level of depression on a scale of 1 to 5 with 5 representing the greatest level of depression.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05849207
Brief Title
Post-Transplant Cyclophosphamide in Patients Aged >/= 70 Years Undergoing Haploidentical Transplant
Acronym
GeriBMT
Official Title
IIT2022-03-Paquette-GeriBMT: A Phase I Study of De-Escalation of Post-Transplant Cyclophosphamide Dosing in Patients Aged >/= 70 Years Undergoing Conditioning With Fludarabine and Total Body Irradiation 800 cGy
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 30, 2023 (Anticipated)
Primary Completion Date
July 1, 2027 (Anticipated)
Study Completion Date
July 1, 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Ronald Paquette
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
The purpose of this phase 1 study is to determine the optimal dose of the immune suppressive drug, cyclophosphamide, following standard allogeneic stem cell transplant in patients aged >/= 70 years with hematologic malignancies.
Detailed Description
The patients will receive a standard dose, or a reduced amount of the immune suppressive drug, cyclophosphamide, that is routinely administered after the transplant procedure. The following procedures will be performed: cardiac MRI scans and/or transthoracic echocardiogram (TTE); laboratory tests, geriatric assessments and tests to measure strength and stability.
Participation in the study is expected to last up to one year with follow-up visits occurring on Day +30, Day +100, Day +180 and Day +365 following allogenic stem cell transplant.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematologic Malignancies
Keywords
Allogeneic Transplantation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Open-label trial
De-escalation of post-transplant cyclophosphamide dosing
Masking
None (Open Label)
Allocation
N/A
Enrollment
26 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Open Arm
Arm Type
Experimental
Arm Description
All patients will receive cyclophosphamide on Day +3 and Day +4 following transplant.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Cyclophosphamide will be administered at 50, 40, 32, or 25 mg/k/d intravenous infusion (IV) continuously for two days starting 60-72 hours after transplant.
Primary Outcome Measure Information:
Title
Maximum grade acute GVHD by day +100 by Modified Keystone Criteria
Description
Evaluate the frequency of grade III/IV acute GVHD using Modified Keystone Criteria
Time Frame
100 days post-transplant
Secondary Outcome Measure Information:
Title
Time to neutrophil and platelet engraftment
Description
Days to neutrophil and platelet engraftment since transplant
Time Frame
60 days post-transplant
Title
Non-Relapse mortality
Description
Rate of treatment-related mortality
Time Frame
100 days post-transplant
Title
Chronic Graft Versus Host Disease (GVHD) at 1 year
Description
Rate and severity of patients with chronic GVHD at day 365 post-transplantation.
Chronic GVHD is when the donated stem cells attack the body after 100 days post-transplant. Chronic GVHD is defined by NIH Consensus Criteria for chronic GVHD.
Time Frame
1-year post-transplant
Title
Relapse
Description
Percentage of patients who relapse by year 1
Time Frame
1-year post-transplant
Title
Overall Survival (OS)
Description
Overall survival at 1 year
Time Frame
1-year post-transplant
Title
Graft Versus Host Disease (GVHD)-free and Relapse Free Survival
Description
Percentage of patients without relapse or GVHD at 1 year
Time Frame
1-year post- transplant
Title
Change in cardiac function
Description
Change in cardiac (heart) injury defined by any of an increase in T1 time > 500 ms from pre-transplant imaging, T2 time > 5 ms from pre-transplant imaging, or a decrease in left ventricular ejection fraction > 10% of the original measurement to below 53% from post-transplant imaging.
Time Frame
From 60 days prior to transplant to 365 days post-transplant
Title
Change in active daily living
Description
Change in function over time as determined by Lawton Activities of Daily Living questionnaire.
- Patients will choose either 0 or 1 to rate their level of function with 1 being the highest level of function.
Time Frame
From 60 days prior to transplant to 365 days post-transplant
Title
Change in function
Description
Change in function over time as determined by the Patient-Reported Outcomes Measurement Information System (PROMIS) Cancer Function Brief 3-Dimensional Profile.
- Patients will rate their physical condition and fatigue using an inverse 5-item likert scale where 5 represents the highest level of function or the greatest amount of impact on function.
Time Frame
From 60 days prior to transplant to 365 days post-transplant
Title
Change in pain
Description
Change in pain over time as determined by the Patient-Reported Outcomes Measurement Information System (PROMIS) Cancer Function Brief 3-Dimensional Profile.
- Patients will rate their level of pain using a scale from 0 to 10 with 10 being the highest level of pain.
Time Frame
From 60 days prior to transplant to 365 days post-transplant
Title
Change in physical function
Description
Change in lower limb functioning over time as evaluated by the Short Physical performance Battery. (SPPB).
- Patients will complete a series of tests evaluating balance, speed and standing capabilities. Patients will be rated using a scale of 0 to 12 where a score of less than 10 indicates mobility limitations.
Time Frame
From 60 days prior to transplant to 365 days post-transplant
Title
Change in grip strength
Description
Change in grip strength as measured using the Jamar dynamometer (device used to measure grip)
Time Frame
From 60 days prior to transplant to 365 days post-transplant
Title
Change in cognitive function
Description
Change in cognitive function over time using the Patient-Reported Outcomes Measurement Information System (PROMIS) Cognition questionnaire.
-Patients will rate their cognitive ability on a scale of 1 to 5 with 5 representing the least amount of difficulty.
Time Frame
From 60 days prior to transplant to 365 days post-transplant
Title
Change in mental health
Description
Change in mental health over time using the Patient-Reported Outcomes Measurement Information System (PROMIS) 29 Depression Questionnaire.
- Patients will rate their level of depression on a scale of 1 to 5 with 5 representing the greatest level of depression.
Time Frame
From 60 days prior to transplant to 365 days post-transplant
10. Eligibility
Sex
All
Minimum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patient age >/= 70 years
Patient has a related donor who is a human leukocyte antigens (HLA) haploidentical match
Patient and Donor sign the Informed Consent Form for the study
Patient meets standard criteria for allogeneic stem cell transplant
Patient is deemed suitable to receive Flu/TBI 800 conditioning regimen as standard of care transplant
Donor is willing to donate peripheral blood stem cells (PBSC)
Exclusion Criteria:
Patient has a diagnosis of myelofibrosis
Patient has high titer antibodies (>10,000 mean fluorescent intensity) against one or more donor HLA antigens
Patient has undergone prior autologous or allogeneic stem cell transplant
Inability to collect at least 3 x 10^6 CD34+ PBSCs/kg recipient weight from the donor
Requiring sedation for cardiac MRIs.
Prohibited Implants and/or Devices:
Mechanical, magnetic or electrical activated implants (i.e. cardiac pacemakers, neurostimulators and infusion pumps)
Ferromagnetic implants and ferromagnetic foreign bodies, such as intracranial, aneurysm clips, shrapnel and intraocular metal chips as these could become dislodged.
Subjects with claustrophobia, problems being in enclosed spaces, or inability to lie supine.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Amy Oppenheim
Phone
310-423-3713
Email
Amy.Oppenheim@cshs.org
First Name & Middle Initial & Last Name or Official Title & Degree
Nadia Nassaj
Phone
310-423-7735
Email
mehrnoosh.nassaj@cshs.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ronald Paquette, MD
Organizational Affiliation
Cedars-Sinai Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amy Oppenheim
Phone
310-423-3713
Email
Amy.Oppenheim@cshs.org
First Name & Middle Initial & Last Name & Degree
Nadia Nassaj
Phone
310-423-7735
Email
mehrnoosh.nassaj@cshs.org
First Name & Middle Initial & Last Name & Degree
John Chute, MD
First Name & Middle Initial & Last Name & Degree
Justin Darrah, MD
First Name & Middle Initial & Last Name & Degree
Akil Merchant, MD
First Name & Middle Initial & Last Name & Degree
Noah Merin, MD, PhD
First Name & Middle Initial & Last Name & Degree
Joshua Sasine, MD, PhD
First Name & Middle Initial & Last Name & Degree
Robert Vescio, MD
First Name & Middle Initial & Last Name & Degree
Arash Asher, MD
First Name & Middle Initial & Last Name & Degree
Philip Chang, MD
First Name & Middle Initial & Last Name & Degree
Alan Kwan, MD
First Name & Middle Initial & Last Name & Degree
Stephen Shiao, MD, PhD
First Name & Middle Initial & Last Name & Degree
Hannah Lee, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Post-Transplant Cyclophosphamide in Patients Aged >/= 70 Years Undergoing Haploidentical Transplant
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