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

NCT07214688 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: Pro2025-0254FLU-TBI-800-PTCY
• Study Type: interventional
• Target: 209
• Locations: 1 country
• Sites: 3

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.

Conditions

Allogeneic Stem Cell Transplant Recipient

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS) at 1-year following treatment with fludarabine plus intermediate-dose total body irradiation (TBI 800 cGy) with post-transplant cyclophosphamide (PTCy)

  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 Outcomes (7)

• 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

• 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, up through a period of 1 year

• 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.

• 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., 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)

  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

Study Arms (1)

Experimental

EXPERIMENTAL

Fludarabine and Intermediate-dose Total Body Irradiation (800 cGy) Followed by Post-transplant Cyclophosphamide

Drug: Fludarabine; Radiation: Intermediate-dose Total Body Irradiation (TBI); Drug: Post-transplant Cyclophosphamide (PTCy); Drug: Tacrolimus; Drug: Mycophenolate mofetil (MMF)

Interventions

Post-transplant Cyclophosphamide (PTCy) DRUG

Patients will receive post-transplant cyclophosphamide (PTCy) administered at the dose of 40 mg/kg intravenously on Days +3 to +4.

Also known as: Cytoxan

Experimental

Tacrolimus DRUG

Patients will receive tacrolimus administered at a dose adjusted to maintain trough levels between 5-15 ng/mL orally starting on Days +5.

Also known as: Prograf

Experimental

Mycophenolate mofetil (MMF) DRUG

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.

Also known as: CellCept

Experimental

Fludarabine DRUG

Patients will receive fludarabine administered at the dose of 30 mg/m2 intravenously daily on Days -6 to -2

Also known as: Fludara, Oforta

Experimental

Intermediate-dose Total Body Irradiation (TBI) RADIATION

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

Experimental

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hackensack Meridian Health: lead

Study Sites (3)

Lombardi Comprehensive Cancer Center at Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

NOT YET RECRUITING

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

RECRUITING

John Theurer Cancer Center at Jersey Shore University Medical Center

Neptune City, New Jersey, 07753, United States

NOT YET RECRUITING

Related Publications (19)

• Martens MJ, Lian Q, Geller NL, Leifer ES, Logan BR. Sequential monitoring of time-to-event safety endpoints in clinical trials. Clin Trials. 2025 Jun;22(3):267-278. doi: 10.1177/17407745241304119. Epub 2024 Dec 29.

  PMID: 40396502 BACKGROUND

• Wu J, Chen L, Wei J, Weiss H, Chauhan A. Two-stage phase II survival trial design. Pharm Stat. 2020 May;19(3):214-229. doi: 10.1002/pst.1983. Epub 2019 Nov 21.

  PMID: 31749311 BACKGROUND

• Mycophenolate REMS (Risk Evaluation and Mitigation Strategy). https://www.accessdata.fda.gov

  BACKGROUND

• Vaxman I, Muchtar E, Jacob E, Kapoor P, Kumar S, Dispenzieri A, Buadi F, Dingli D, Gonsalves W, Kourelis T, Warsame R, Lacy M, Hogan W, Gertz MA. The Efficacy and Safety of Chemotherapy-Based Stem Cell Mobilization in Multiple Myeloma Patients Who Are Poor Responders to Induction: The Mayo Clinic Experience. Transplant Cell Ther. 2021 Sep;27(9):770.e1-770.e7. doi: 10.1016/j.jtct.2021.06.016. Epub 2021 Jun 18.

  PMID: 34153504 BACKGROUND

• Xhaard A, Rocha V, Bueno B, de Latour RP, Lenglet J, Petropoulou A, Rodriguez-Otero P, Ribaud P, Porcher R, Socie G, Robin M. Steroid-refractory acute GVHD: lack of long-term improved survival using new generation anticytokine treatment. Biol Blood Marrow Transplant. 2012 Mar;18(3):406-13. doi: 10.1016/j.bbmt.2011.06.012. Epub 2011 Jul 4.

  PMID: 21736868 BACKGROUND

• Sengsayadeth S, Wang T, Lee SJ, Haagenson MD, Spellman S, Fernandez Vina MA, Muller CR, Verneris MR, Savani BN, Jagasia M. Cytotoxic T-lymphocyte antigen-4 single nucleotide polymorphisms are not associated with outcomes after unrelated donor transplantation: a center for international blood and marrow transplant research analysis. Biol Blood Marrow Transplant. 2014 Jun;20(6):900-3. doi: 10.1016/j.bbmt.2014.03.005. Epub 2014 Mar 14.

  PMID: 24631737 BACKGROUND

• Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995 Jun;15(6):825-8.

  PMID: 7581076 BACKGROUND

• Lee JW, Cho BS, Lee SE, Eom KS, Kim YJ, Kim HJ, Lee S, Min CK, Cho SG, Min WS, Park CW. The Outcome of Unrelated Hematopoietic Stem Cell Transplants with Total Body Irradiation (800 cGy) and Cyclophosphamide (120 mg/kg) in Adult Patients with Acquired Severe Aplastic Anemia. Biol Blood Marrow Transplant. 2011 Jan;17(1):101-8. doi: 10.1016/j.bbmt.2010.06.014. Epub 2010 Jun 25.

  PMID: 20601037 BACKGROUND

• Sanchez-Petitto G, Huang Y, Bezerra E, et al. Comparison of Two Myeloablative Total-Body Irradiation (MAC-TBI) Regimens: 1200 Cgy Vs 800 Cgy of TBI for Allogeneic Stem Cell Transplantation in Adults with Hematological Malignancies. Blood. 2024;144(Supplement 1):7303-7303. doi:10.1182/blood-2024-194146

  BACKGROUND

• Sterling CH, Hughes MS, Tsai HL, et al. Non-myeloablative allogeneic blood or marrow transplantation (AlloBMT) with post-transplant cyclophosphamide (PTCy) for peripheral T- cell lymphoma (PTCL): Improved outcomes with peripheral blood (PB) allografts and increased total body irradiation (TBI) to 400 cGV. J Clin Oncol. 2022;40(16_suppl):7047- 7047. doi:10.1200/JCO.2022.40.16_suppl.7047

  BACKGROUND

• Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M, Martin PJ, Sandmaier BM, Marr KA, Appelbaum FR, Storb R, McDonald GB. Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med. 2010 Nov 25;363(22):2091-101. doi: 10.1056/NEJMoa1004383.

  PMID: 21105791 BACKGROUND

• Ciurea S, Zhang M, Kanakry C. CNIs versus post-transplant cyclophosphamide-based GVHD prophylaxis in haploidentical transplantation. Blood. 2020;137(4):444-455.

  BACKGROUND

• Kanakry CG, Tsai HL, Bolanos-Meade J, Smith BD, Gojo I, Kanakry JA, Kasamon YL, Gladstone DE, Matsui W, Borrello I, Huff CA, Swinnen LJ, Powell JD, Pratz KW, DeZern AE, Showel MM, McDevitt MA, Brodsky RA, Levis MJ, Ambinder RF, Fuchs EJ, Rosner GL, Jones RJ, Luznik L. Single-agent GVHD prophylaxis with posttransplantation cyclophosphamide after myeloablative, HLA-matched BMT for AML, ALL, and MDS. Blood. 2014 Dec 11;124(25):3817-27. doi: 10.1182/blood-2014-07-587477. Epub 2014 Oct 14.

  PMID: 25316679 BACKGROUND

• Bolanos-Meade J, Hamadani M, Wu J, Al Malki MM, Martens MJ, Runaas L, Elmariah H, Rezvani AR, Gooptu M, Larkin KT, Shaffer BC, El Jurdi N, Loren AW, Solh M, Hall AC, Alousi AM, Jamy OH, Perales MA, Yao JM, Applegate K, Bhatt AS, Kean LS, Efebera YA, Reshef R, Clark W, DiFronzo NL, Leifer E, Horowitz MM, Jones RJ, Holtan SG; BMT CTN 1703 Investigators. Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis. N Engl J Med. 2023 Jun 22;388(25):2338-2348. doi: 10.1056/NEJMoa2215943.

  PMID: 37342922 BACKGROUND

• Luznik L, O'Donnell PV, Fuchs EJ. Post-transplantation cyclophosphamide for tolerance induction in HLA-haploidentical bone marrow transplantation. Semin Oncol. 2012 Dec;39(6):683-93. doi: 10.1053/j.seminoncol.2012.09.005.

  PMID: 23206845 BACKGROUND

• Scott BL, Pasquini MC, Logan BR, Wu J, Devine SM, Porter DL, Maziarz RT, Warlick ED, Fernandez HF, Alyea EP, Hamadani M, Bashey A, Giralt S, Geller NL, Leifer E, Le-Rademacher J, Mendizabal AM, Horowitz MM, Deeg HJ, Horwitz ME. Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes. J Clin Oncol. 2017 Apr 10;35(11):1154-1161. doi: 10.1200/JCO.2016.70.7091. Epub 2017 Feb 13.

  PMID: 28380315 BACKGROUND

• Copelan EA. Hematopoietic stem-cell transplantation. N Engl J Med. 2006 Apr 27;354(17):1813-26. doi: 10.1056/NEJMra052638. No abstract available.

  PMID: 16641398 BACKGROUND

• Baron F, Labopin M, Blaise D. Reduced-intensity conditioning versus myeloablative conditioning allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia: A study from the Acute Leukemia Working Party of the EBMT. Blood. 2017;129(4):448-456.

  BACKGROUND

• Gyurkocza B, Rezvani A, Storb RF. Allogeneic hematopoietic cell transplantation: the state of the art. Expert Rev Hematol. 2010 Jun;3(3):285-99. doi: 10.1586/ehm.10.21.

  PMID: 20871781 BACKGROUND

MeSH Terms

Interventions

fludarabine; fludarabine phosphate; Cyclophosphamide; Tacrolimus; Mycophenolic Acid

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Study Officials

• Michele Donato, MD

  Hackensack Meridian Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Oncology Clinical Research Referral Office

CONTACT

551-996-1777; OncologyResearchReferral@hmhn.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2025
• First Posted: October 9, 2025
• Study Start: January 6, 2026
• Primary Completion (Estimated): January 1, 2032
• Study Completion (Estimated): January 1, 2032
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)