Post-Transplant Cyclophosphamide in Patients Aged >/= 70 Years Undergoing Haploidentical Transplant

Study Overview
=================
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.

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

Conditions
-----------------
Hematologic Malignancies

Intervention / Treatment
-----------------
* Drug: Cyclophosphamide


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: Open-label trial De-escalation of post-transplant cyclophosphamide dosing
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open Arm<br>All patients will receive cyclophosphamide on Day +3 and Day +4 following transplant. | Drug: Cyclophosphamide<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum grade acute GVHD by day +100 by Modified Keystone Criteria | Evaluate the frequency of grade III/IV acute GVHD using Modified Keystone Criteria | 100 days post-transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to neutrophil and platelet engraftment | Days to neutrophil and platelet engraftment since transplant | 60 days post-transplant | 
| Non-Relapse mortality | Rate of treatment-related mortality | 100 days post-transplant | 
| 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. | 1-year post-transplant | 
| Relapse | Percentage of patients who relapse by year 1 | 1-year post-transplant | 
| Overall Survival (OS) | Overall survival at 1 year | 1-year post-transplant | 
| Graft Versus Host Disease (GVHD)-free and Relapse Free Survival | Percentage of patients without relapse or GVHD at 1 year | 1-year post- transplant | 
| 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. | From 60 days prior to transplant to 365 days post-transplant | 
| 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. | From 60 days prior to transplant to 365 days post-transplant | 
| 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. | From 60 days prior to transplant to 365 days post-transplant | 
| 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. | From 60 days prior to transplant to 365 days post-transplant | 
| 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. | From 60 days prior to transplant to 365 days post-transplant | 
| Change in grip strength | Change in grip strength as measured using the Jamar dynamometer (device used to measure grip) | From 60 days prior to transplant to 365 days post-transplant | 
| 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. | From 60 days prior to transplant to 365 days post-transplant | 
| 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. | From 60 days prior to transplant to 365 days post-transplant | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Allogeneic Transplantation