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

March 20, 2026 updated by: Hackensack Meridian Health

A Phase 2 Study of Fludarabine and Intermediate-dose Total Body Irradiation (800 cGy) Followed by Post-transplant Cyclophosphamide in Patients Aged 18-65 Undergoing Allogeneic Stem Cell Transplant for Hematologic Malignancies

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

209

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • Not yet recruiting
        • Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
        • Contact:
          • Pending
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Recruiting
        • John Theurer Cancer Center at Hackensack University Medical Center
        • Contact:
      • Neptune City, New Jersey, United States, 07753
        • Not yet recruiting
        • John Theurer Cancer Center at Jersey Shore University Medical Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental
Fludarabine and Intermediate-dose Total Body Irradiation (800 cGy) Followed by Post-transplant Cyclophosphamide
Drug: Fludarabine
Patients will receive fludarabine administered at the dose of 30 mg/m2 intravenously daily on Days -6 to -2
Other Names:
  • Fludara
  • Oforta
Radiation: Intermediate-dose Total Body Irradiation (TBI)
Patients will receive intermediate-dose total body irradiation (TBI) administered at the dose of 800 cGy in 4 total fractions, 2 fractions per day on Days -2 to -1
Drug: Post-transplant Cyclophosphamide (PTCy)
Patients will receive post-transplant cyclophosphamide (PTCy) administered at the dose of 40 mg/kg intravenously on Days +3 to +4.
Other Names:
  • Cytoxan
Drug: Tacrolimus
Patients will receive tacrolimus administered at a dose adjusted to maintain trough levels between 5-15 ng/mL orally starting on Days +5.
Other Names:
  • Prograf
Drug: Mycophenolate mofetil (MMF)
Patients will receive mycophenolate mofetil (MMF) administered at the standard dose of 15 mg/kg orally three times daily starting on Day +5 to Day +35 or per institutional guidelines.
Other Names:
  • CellCept

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS) at 1-year following treatment with fludarabine plus intermediate-dose total body irradiation (TBI 800 cGy) with post-transplant cyclophosphamide (PTCy)
Time Frame: 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
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.
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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
Time Frame: 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."
Patients will be assessed for chronic GVHD signs and/or symptoms at a minimum of every three months for the first year post-transplant.
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)
Time Frame: 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
TRM is defined as death due to causes unrelated to the underlying disease. Patients relapsing are censored as surviving at the time of relapse.
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
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)
Time Frame: 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, up through a period of 1 year
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."
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, up through a period of 1 year
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)
Time Frame: Patient status (GVHD-free, relapse-free or not) will be reviewed (e.g., throughpatient chart review, patient phone call, etc.) up through a period of 1 year
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.
Patient status (GVHD-free, relapse-free or not) will be reviewed (e.g., throughpatient chart review, patient phone call, etc.) up through a period of 1 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)
Time Frame: 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
Disease status assessment is based on the CIBMTR criterion (see section 8 for more information).
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
Relapse rate at 1-year following treatment with fludarabine plus intermediate-dose total body irradiation (TBI 800 cGy) with post-transplant cyclophosphamide (PTCy)
Time Frame: Patient status (relapse or continued response) will be reviewed (e.g., throughpatient chart review, patient phone call, etc.) up through a period of 1 year
Relapse is based on the CIBMTR criterion (see section 8 for more information).
Patient status (relapse or continued response) will be reviewed (e.g., throughpatient chart review, patient phone call, etc.) up through a period of 1 year
Incidence of Treatment-Emergent Adverse Events with fludarabine plus intermediate-dose total body irradiation (TBI 800 cGy) with post-transplant cyclophosphamide (PTCy)
Time Frame: Following treatment and allogeneic stem cell transplant, all participants will befollowed for safety throughout treatment and the hospital admission as well as longer termsafety 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.
Following treatment and allogeneic stem cell transplant, all participants will befollowed for safety throughout treatment and the hospital admission as well as longer termsafety follow-up assessments every 3 months for a period of approximately 1 year.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hackensack Meridian Health

Investigators

  • Principal Investigator: Michele Donato, MD, Hackensack Meridian Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 6, 2026

Primary Completion (Estimated)

January 1, 2032

Study Completion (Estimated)

January 1, 2032

Study Registration Dates

First Submitted

October 3, 2025

First Submitted That Met QC Criteria

October 3, 2025

First Posted (Actual)

October 9, 2025

Study Record Updates

Last Update Posted (Actual)

March 23, 2026

Last Update Submitted That Met QC Criteria

March 20, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro2025-0254 (HMH)
  • FLU-TBI-800-PTCY (Other Identifier: HMH)

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.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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