Fludarabine and Intermediate-dose TBI Followed by PTCy in Patients Undergoing Allo Transplant for Heme Malignancies

Not Applicable

Not yet recruiting

• Conditions: Allogeneic Stem Cell Transplant Recipient
• Interventions: Drug: Fludarabine; Radiation: Intermediate-dose Total Body Irradiation (TBI); Drug: Post-transplant Cyclophosphamide (PTCy); Drug: Tacrolimus; Drug: Mycophenolate mofetil (MMF)

• Registration Number: NCT07214688
• Lead Sponsor: Hackensack Meridian Health

Brief Summary

The Flu-TBI 800 trial is a prospective, single-arm, multicenter, interventional phase 2 study to evaluate whether fludarabine plus intermediate-dose total body irradiation (TBI 800 cGy) with post-transplant cyclophosphamide (PTCy) (experimental regimen) improves the 1-year survival of allogeneic stem cell transplant recipients.

Detailed Description

Patients who meet all the inclusion criteria for the study will be enrolled to receive a conditioning regimen consisting of fludarabine, administered at a dose of 30 mg/m2 daily on Days -6 to -2, plus intermediate-dose total body irradiation (TBI), administered at a dose of 800 cGy in 4 total fractions, 2 fractions on Days -2 and and 2 fractions on day -1, followed by an infusion of hematopoietic stem cells on Day 0. GVHD prophylaxis will consist of post-transplant cyclophosphamide (PTCy), administered at a dose of 40 mg/kg on Days +3 and +4, as well as tacrolimus (starting on Day +5) and mycophenolate mofetil (on Days +5 to +35).

Study Timeline

• Status Verified: 2025-10
• Study First Submitted: 2025-10-03
• Study First Submitted QC: 2025-10-03
• Last Update Submitted: 2025-10-03
• Study First Posted: 2025-10-09
• Last Update Posted: 2025-10-09
• Study Start: 2025-10-15
• Primary Completion: 2031-10-15
• Study Completion: 2031-10-15

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 209

Inclusion Criteria

• Patients ages 18-65 years.

• Patients with a diagnosis of one of the following hematologic malignancies:

• Acute myeloid leukemia or chronic myeloid leukemia with no circulating blasts and less than 5% blasts in the bone marrow;

• Myelodysplastic syndrome with less than 5% blasts in the bone marrow by IHC or flow cytometry whichever is highest;

• Myeloproliferative neoplasms with less than 5% blast in the marrow and peripheral blood;

• Acute lymphoblastic leukemia in CR (CIBMTR criteria); or Lymphoma in CR (CIBMTR criteria).

• Patients who are eligible for allogeneic stem cell transplant per Transplant Program SOPs.

• Patients with a Karnofsky performance status (KPS) of ≥60%.

• Patients with adequate organ function defined by:

  • Cardiac: LVEF ≥50%
  • Pulmonary: DLCO ≥50% of predicted
  • Hepatic: Bilirubin ≤1.5x ULN, ALT/AST ≤2.5x ULN
  • Renal: Creatinine clearance ≥50 mL/min

• All participants of reproductive potential must use effective contraception following allogeneic hematopoietic stem cell transplantation (allo-HSCT), in accordance with guidelines from the American Society for Transplantation and Cellular Therapy (ASTCT), the FDA, and other expert bodies.

• For Male Participants:

  ○ Male participants must use effective contraception for at least 12 months after transplant, and longer if receiving immunosuppressive or cytotoxic medications. Chemotherapy and radiation can cause DNA damage to sperm, and even if fertility returns, mutations may persist for months. In cases where drugs such as mycophenolate mofetil (MMF) or lenalidomide are used, FDA guidance requires contraception for at least 90 days after discontinuation. Sperm cryopreservation should be offered prior to conditioning. Participants must avoid fathering a child during this time frame.15-17

• For Female Participants:

  • Female participants of childbearing potential are required to use highly effective contraception for a minimum of 12 to 24 months post-transplant, or longer if still receiving immunosuppressive or teratogenic therapy. For drugs such as MMF, sirolimus, or ruxolitinib, contraception must continue for 3 months after the last dose.
  • A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements.15-17

• Patients with a suitable donor for allogeneic stem cell transplant defined by:

  • Matched sibling donors willing to donate mobilized peripheral blood (PBSC) or bone marrow (BM), meeting all institutional criteria for donation;
  • Unrelated donors at >7/8 (i.e., mismatched at only one of the HLA-A, HLA-B, HLA-C, and HLA-DRB1 loci) willing to donate mobilized PBSC or BM, and medically eligible to donate cells according to National Marrow Donor Program criteria; or Related Haploidentical donors willing to donate PBSC or BM and meeting criteria for donation.

• Patients who are able to comply with follow-up visits and treatment plans.

• Patients who are able to give informed consent.

Exclusion Criteria

• Hematopoietic cell transplantation comorbidity index above 3.
• Patients with a Karnofsky performance status (KPS) of <60%.
• Patients with active infections or other contraindications for allogeneic stem cell transplant.
• Patients who are unable or unwilling to give informed consent.
• Patients who have received a prior allogeneic transplant.
• Patients who are unable to comply with follow-up visits and treatment plans.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental	Fludarabine	Fludarabine and Intermediate-dose Total Body Irradiation (800 cGy) Followed by Post-transplant Cyclophosphamide
Experimental	Intermediate-dose Total Body Irradiation (TBI)	Fludarabine and Intermediate-dose Total Body Irradiation (800 cGy) Followed by Post-transplant Cyclophosphamide
Experimental	Post-transplant Cyclophosphamide (PTCy)	Fludarabine and Intermediate-dose Total Body Irradiation (800 cGy) Followed by Post-transplant Cyclophosphamide
Experimental	Tacrolimus	Fludarabine and Intermediate-dose Total Body Irradiation (800 cGy) Followed by Post-transplant Cyclophosphamide
Experimental	Mycophenolate mofetil (MMF)	Fludarabine and Intermediate-dose Total Body Irradiation (800 cGy) Followed by Post-transplant Cyclophosphamide

Primary Outcome Measures

Name	Time	Method
Overall survival (OS) at 1-year following treatment with fludarabine plus intermediate-dose total body irradiation (TBI 800 cGy) with post-transplant cyclophosphamide (PTCy)	Patient status (dead or alive) will be reviewed (e.g., through patient chart review, patient phone call, etc.) up through a period of 1 year and we will collect this data.	OS is defined as the time from the first dose of study treatment to the time of death due to any cause. Patients who are still alive will be censored at the date last known alive of the data cut-off date (if applicable), whichever is earlier.

Secondary Outcome Measures

Name	Time	Method
Transplant-related mortality (TRM) at 1-year following treatment with fludarabine plus intermediate-dose total body irradiation (TBI 800 cGy) with post-transplant cyclophosphamide (PTCy)	Patient status (dead or alive) will be reviewed (e.g., through patient chart review, patient phone call, etc.) up through a period of 1 year and we will collect this data.	TRM is defined as death due to causes unrelated to the underlying disease. Patients relapsing are censored as surviving at the time of relapse.
Incidence of grade III-IV acute GVHD following treatment with fludarabine plus intermediate-dose total body irradiation (TBI 800 cGy) with post-transplant cyclophosphamide (PTCy)	Patients will be assessed for acute GVHD symptoms weekly from day +7 until day +100. If acute GVHD symptoms remain active after day +100, weekly GVHD documentation will be encouraged until symptom(s) resolution, as per HMH's SOP BMT 500 15.	Acute GVHD will be assessed using the Przepiorka criteria,13 Modified Glucksberg/Keystone criteria, and Center for International Blood and Marrow Transplant Research (CIBMTR) severity index (A-D) according to HMH's standard operating procedure (SOP), "Management of Acute Graft versus Host Disease, BMT 500 15."
Incidence of chronic GVHD at 1-year following treatment with fludarabine plus intermediate-dose total body irradiation (TBI 800 cGy) with post-transplant cyclophosphamide (PTCy)	Patients will be assessed for chronic GVHD signs and/or symptoms at a minimum of every three months for the first year post-transplant.	Chronic GVHD will be assessed based on the 2014 National Institutes of Health (NIH) Consensus Conference Criteria according to HMH's SOP, "Chronic Graft Versus Host Disease, BMT 500 11."
GVHD-free, relapse-free survival (GRFS) at 1-year following treatment with fludarabine plus intermediate-dose total body irradiation (TBI 800 cGy) with post-transplant cyclophosphamide (PTCy)	Patient status (GVHD-free, relapse-free or not) will be reviewed (e.g., through patient chart review, patient phone call, etc.) up through a period of 1 year and we will collect this data.	GVHD-free, relapse-free survival (GRFS) is a composite endpoint that includes grades 3-4 acute GVHD, chronic GVHD requiring systemic therapy, relapse, or death in the first post-transplant year.
Disease status assessment 2-4 months following treatment with fludarabine plus intermediate-dose total body irradiation (TBI 800 cGy) with post-transplant cyclophosphamide (PTCy)	Patient disease status assessments (e.g., PET-CT, bone marrow, peripheral blood, etc.) will be reviewed (e.g., through patient chart review, etc.) up through a period of 2-4 months following treatment and we will collect this data.	Disease status assessment is based on the CIBMTR criterion (see section 8 for more information).
Relapse rate at 1-year following treatment with fludarabine plus intermediate-dose total body irradiation (TBI 800 cGy) with post-transplant cyclophosphamide (PTCy)	Patient status (relapse or continued response) will be reviewed (e.g., through patient chart review, patient phone call, etc.) up through a period of 1 year and we will collect this data.	Relapse is based on the CIBMTR criterion (see section 8 for more information).
Safety of treatment with fludarabine plus intermediate-dose total body irradiation (TBI 800 cGy) with post-transplant cyclophosphamide (PTCy)	Following treatment and allogeneic stem cell transplant, all participants will be followed for safety throughout treatment and the hospital admission as well as longer term safety follow-up assessments every 3 months for a period of approximately 1 year.	Adverse events (AEs) will be assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 or severity grade when CTCAE grading does not exist. Grade 1 to 5 will be used to characterize the severity of the AE. If CTCAE grading does not exist for an AE, the severity of mild, moderate, severe, life-threatening and death due to the AE, corresponding respectively to Grades 1 - 5, will be used. This grading system applies except for hematological toxicity where grade 4 cytopenias are anticipated in transplant recipients.

Trial Locations

Locations (3)

Lombardi Comprehensive Cancer Center at Georgetown University Medical Center; 🇺🇸 Washington D.C., District of Columbia, United States

John Theurer Cancer Center at Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States

John Theurer Cancer Center at Jersey Shore University Medical Center; 🇺🇸 Neptune City, New Jersey, United States