Clinical trial NCT06799195: Optimizing GVHD Prophylaxis After Allogeneic Hematopoietic Cell Transplantation
Official title: A Phase II Randomized Trial to Optimize GVHD Prophylaxis After Allogeneic Hematopoietic Cell Transplantation in Older Adults With Hematological Malignancies: the PROMISE Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Hematological Malignancies
Graft-versus-Host Disease (GVHD)
Keywords: Allogeneic Hematopoietic Stem Cell Transplantation
GVHD Prophylaxis
Sirolimus
Mycophenolate Mofetil (MMF)
Health-Related Quality of Life (HRQoL)
Randomized Controlled Trial
Lead sponsor: University of Nebraska
Sponsor class: OTHER
First posted: 2025-01-29
Enrollment: 126
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a single-center, randomized, phase II trial comparing two graft-versus-host disease (GVHD) prophylaxis regimens in older adults undergoing allogeneic hematopoietic stem cell transplantation. Participants are randomized into two arms: high-dose (standard care) versus attenuated-dose post-transplant cyclophosphamide (PTCy), both in addition to sirolimus and mycophenolate mofetil (MMF).
Primary purpose: TREATMENT

Brief summary: This study will compare post-transplant health-related quality of life following the use of standard versus attenuated dose of post-transplant cyclophosphamide in addition to two-drug graft-versus-host disease (GVHD) prophylaxis among recipients of allogeneic hematopoietic stem cell transplant.

Detailed description: This is a single-center phase II study of 126 participants (63 per arm) with hematological malignancies. Participants will be randomized to receive high doses (standard arm) or attenuated doses of cyclophosphamide in addition to two-drug GVHD prophylaxis. Participants will be monitored for health-related quality of life \[Functional Assessment of Cancer Therapy-Bone Marrow Transplant, FACT-BMT(1)\], functional outcomes (Karnofsky Performance Scale (KPS), activities of daily living, instrumental activities of daily living, Clock-in-the-Box Test, Fried Frailty Index, fall history, BMI, and Geriatric Depression Scale-15, GVHD, relapse, survival, and toxicities (using Common Terminology Criteria for Adverse Events, CTCAE version 5.0).

Eligibility criteria: Inclusion criteria:

* Adults aged 60 years or older
* Diagnosis of a hematological malignancy or other serious hematological disorder that requires an allogeneic hematopoietic cell transplantation
* Planned to receive any reduced-intensity conditioning regimen (any graft source is acceptable) and availability of human leukocyte antigen (HLA)-matched donor at HLA loci A, B, C, and HLA-DR beta chain antigen (DRB1)
* Karnofsky Performance Status (KPS) of 70% or higher.

Exclusion criteria:

* Previous history of one or more prior allogeneic stem cell transplants (i.e., second or third allogeneic transplant)
* Planned use of high doses of cyclophosphamide (e.g., a total cyclophosphamide dose of approximately 50 mg/kg or more) as part of the conditioning regimen prior to allogeneic stem cell transplant. A lower dose of cyclophosphamide (e.g., fludarabine, cyclophosphamide, and low-dose total body irradiation regimen that uses 2 doses of cyclophosphamide at 14.5 mg/kg) is acceptable.
* Known diagnosis of liver cirrhosis or other advanced liver disease that may impact cyclophosphamide metabolism.
* Diagnosis of myelofibrosis
* Creatinine clearance less than 40 mL/min/1.73 m², which may increase the risk of hemorrhagic cystitis with post-transplant cyclophosphamide (PTCy)
* Systolic cardiac dysfunction with an ejection fraction of less than 45%.
* Use of a haploidentical or mismatched donor.
* Any other condition judged by the physician to increase the risk of toxicities associated with PTCy.

Primary outcomes:
measure: Change in Health-Related Quality of Life as Measured by Functional Assessment of Cancer Therapy-Bone Marrow Transplantation
timeFrame: Baseline and 3 months post-transplant
Secondary outcomes:
measure: Change in Karnofsky Performance Scale
timeFrame: Baseline and 3 months post-transplant
measure: Change in Activities of Daily Living
timeFrame: Baseline and 3 months post-transplant
measure: Change in Instrumental Activities of Daily Living
timeFrame: Baseline and 3 months post-transplant
measure: Change in Fried Frailty Index
timeFrame: Baseline and 3 months post-transplant
measure: Change in Clock-in-the-Box Test
timeFrame: Baseline and 3 months post-transplant
measure: Change in History of Falls
timeFrame: Baseline and 3 months post-transplant
measure: Change in Body Mass Index
timeFrame: Baseline and 3 months post-transplant
measure: Change in Geriatric Depression Scale-15
timeFrame: Baseline and 3 months post-transplant
measure: Gaft-Versus-Host Disease-Free, Relapse-Free Survival
timeFrame: From date of transplant to 1 year post-transplant
measure: Overall Survival at 1 Year Post-Transplant and Event-Free Survival
timeFrame: From date of transplant to 1 year post-transplant
measure: Cumulative Incidence of Transplant-Related Mortality
timeFrame: From date of transplant to 1 year post-transplant
measure: Cumulative Incidence of Grade II-IV Acute GVHD
timeFrame: From date of transplant to 1 year post-transplant
measure: Cumulative Incidence of Chronic GVHD
timeFrame: From date of transplant to 1 year post-transplant
measure: To determine the cumulative incidence and kinetics of hematologic recovery (neutrophil and platelet) among the two treatment arms
timeFrame: From date of transplant to day +28 and day +100 post-transplant
measure: Incidence of Grade III or Higher Adverse Events
timeFrame: From date of transplant to day +100 post-transplant
measure: Cumulative Incidence of Grade II or Higher Infections
timeFrame: From date of transplant to 6 months post-transplant
Other outcomes:
Locations:
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
Study officials:
affiliation: University of Nebraska
name: Vijaya R Bhatt, MBBS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Luznik L, Pasquini MC, Logan B, Soiffer RJ, Wu J, Devine SM, Geller N, Giralt S, Heslop HE, Horowitz MM, Jones RJ, Litzow MR, Mendizabal A, Muffly L, Nemecek ER, O'Donnell L, O'Reilly RJ, Palencia R, Schetelig J, Shune L, Solomon SR, Vasu S, Ho VT, Perales MA. Randomized Phase III BMT CTN Trial of Calcineurin Inhibitor-Free Chronic Graft-Versus-Host Disease Interventions in Myeloablative Hematopoietic Cell Transplantation for Hematologic Malignancies. J Clin Oncol. 2022 Feb 1;40(4):356-368. doi: 10.1200/JCO.21.02293. Epub 2021 Dec 2.
citation: Korngold R, Sprent J. Lethal graft-versus-host disease after bone marrow transplantation across minor histocompatibility barriers in mice. Prevention by removing mature T cells from marrow. J Exp Med. 1978 Dec 1;148(6):1687-98. doi: 10.1084/jem.148.6.1687.
citation: Wingard JR, Majhail NS, Brazauskas R, Wang Z, Sobocinski KA, Jacobsohn D, Sorror ML, Horowitz MM, Bolwell B, Rizzo JD, Socie G. Long-term survival and late deaths after allogeneic hematopoietic cell transplantation. J Clin Oncol. 2011 Jun 1;29(16):2230-9. doi: 10.1200/JCO.2010.33.7212. Epub 2011 Apr 4.
citation: McQuellon RP, Russell GB, Cella DF, Craven BL, Brady M, Bonomi A, Hurd DD. Quality of life measurement in bone marrow transplantation: development of the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) scale. Bone Marrow Transplant. 1997 Feb;19(4):357-68. doi: 10.1038/sj.bmt.1700672.