Post-Transplant Cyclophosphamide in Patients Aged >/= 65 Years Undergoing Haploidentical Transplant (GeriBMT)

IIT2022-03-Paquette-GeriBMT: A Phase I Study of De-Escalation of Post-Transplant Cyclophosphamide Dosing in Patients Aged >/= 65 Years Undergoing Conditioning With Fludarabine and Total Body Irradiation 800 cGy

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 >/= 65 years with hematologic malignancies.

Study Overview

• Status: Recruiting
• Conditions: Hematologic Malignancies
• Intervention / Treatment: Drug: Cyclophosphamide

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 Type: Interventional
• Enrollment (Estimated): 26
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Trials Navigator; Phone Number: 310-423-3713; Email: GroupCancerTrialInformation@cshs.org

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars-Sinai Medical Center
      • Sub-Investigator: Akil Merchant, MD
      • Sub-Investigator: Justin Darrah, MD
      • Sub-Investigator: Arash Asher, MD
      • Sub-Investigator: John Chute, MD
      • Sub-Investigator: Robert Vescio, MD
      • Sub-Investigator: Stephen Shiao, MD, PhD
      • Sub-Investigator: Noah Merin, MD, PhD
      • Sub-Investigator: Joshua Sasine, MD, PhD
      • Sub-Investigator: Philip Chang, MD
      • Sub-Investigator: Alan Kwan, MD
      • Sub-Investigator: Hannah Lee, MD
      • Contact: Clinical Trial Recruitment Navigator; Phone Number: 13104232133; Email: GroupCancerTrialInformation@cshs.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient age >/= 65 years
• Patient and related Donor (if applicable) sign the Informed Consent Form for the study. If donor is unrelated, donor does not sign Informed Consent Form and this will not affect recipient study eligibility.
• 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

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
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

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

Collaborators and Investigators

• Sponsor: Ronald Paquette
• Investigators: Principal Investigator: Ronald Paquette, MD, Cedars-Sinai Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2023
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: April 13, 2023
• First Submitted That Met QC Criteria: May 5, 2023
• First Posted (Actual): May 8, 2023

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 1, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Allogeneic Transplantation
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Hematologic Neoplasms; Organic Chemicals; Hydrocarbons; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cyclophosphamide
• Other Study ID Numbers: IIT2022-03-PAQUETTE-GERIBMT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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