GeriBMT: Post-Transplant Cyclophosphamide in Patients Aged >/=70 Years Undergoing Haploidentical Transplant
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Open Arm All patients will receive cyclophosphamide on Day +3 and Day +4 following transplant. |
Drug: Cyclophosphamide
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.
|
Outcome Measures
Primary Outcome Measures
- Maximum grade acute GVHD by day +100 by Modified Keystone Criteria [100 days post-transplant]
Evaluate the frequency of grade III/IV acute GVHD using Modified Keystone Criteria
Secondary Outcome Measures
- Time to neutrophil and platelet engraftment [60 days post-transplant]
Days to neutrophil and platelet engraftment since transplant
- Non-Relapse mortality [100 days post-transplant]
Rate of treatment-related mortality
- Chronic Graft Versus Host Disease (GVHD) at 1 year [1-year post-transplant]
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 [1-year post-transplant]
Percentage of patients who relapse by year 1
- Overall Survival (OS) [1-year post-transplant]
Overall survival at 1 year
- Graft Versus Host Disease (GVHD)-free and Relapse Free Survival [1-year post- transplant]
Percentage of patients without relapse or GVHD at 1 year
- Change in cardiac function [From 60 days prior to transplant to 365 days post-transplant]
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 [From 60 days prior to transplant to 365 days post-transplant]
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 [From 60 days prior to transplant to 365 days post-transplant]
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 [From 60 days prior to transplant to 365 days post-transplant]
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 [From 60 days prior to transplant to 365 days post-transplant]
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 [From 60 days prior to transplant to 365 days post-transplant]
Change in grip strength as measured using the Jamar dynamometer (device used to measure grip)
- Change in cognitive function [From 60 days prior to transplant to 365 days post-transplant]
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 [From 60 days prior to transplant to 365 days post-transplant]
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.
Eligibility Criteria
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
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cedars-Sinai Medical Center | Los Angeles | California | United States | 90048 |
Sponsors and Collaborators
- Ronald Paquette
Investigators
- Principal Investigator: Ronald Paquette, MD, Cedars-Sinai Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IIT2022-03-PAQUETTE-GERIBMT