Thiotepa-based Conditioning Regimen With De-escalated Post-graft Cyclophosphamide for Allogeneic Stem Cell Transplantation in Hematologic Malignancies

NCT07565220 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: HCC 26-008
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This phase 1 trial will investigate the safety and effectiveness of Thiotepa, Busulfan, and Fludarabine (TBF) conditioning regimen with post-transplant cyclophosphamide (PTCy) in HLA-matched related or unrelated donor allogeneic stem cell transplantation (alloSCT).

Conditions

Acute Myeloid Leukemia (AML); Acute Leukemia; Myelodysplastic Syndrome(MDS); High-risk Myeloproliferative Neoplasm (MPN); Acute Lymphocytic Leukemia (ALL)

Keywords

allogeneic hematopoietic stem cell transplantation; HLA; graft-versus-host disease (GVHD)

Outcome Measures

Primary Outcomes (1)

• GVHD-free, relapse-free survival (GRFS)

  Graft Versus Host Disease (GVHD)-free, relapse-free survival (GRFS) is defined by survival without a qualifying event including Death, Relapse of primary disease, Grade III-IV acute graft-versus-host disease (GVHD), graded via MAGIC criteria, Chronic moderate or severe GVHD requiring systemic immunosuppression, graded via NIH consensus criteria.

  At 1 year

Secondary Outcomes (10)

• Median time to neutrophil engraftment

  Up to 30 days

• Median time to platelet engraftment

  Up to 30 days

• Frequency of severe mucositis

  Up to 30 days post-transplant

• Frequency of total parental nutrition

  Up to 30 days post-transplant

• Frequency of severe pulmonary complications requiring ICU-level support

  Up to 30 days

Study Arms (2)

Cohort 1: T1FluBu2 (low-intensity)

EXPERIMENTAL

Thiotepa: 5 mg/kg - administered on Day -5 prior to PBSC infusion Fludarabine: 30 mg/m2/day - administered on Day -4, Day -3, Day -2 and Day -1 prior to PBSC infusion Busulfan: 3.2 mg/kg/day IV - administered on Day -4 and Day -3 prior to PBSC infusion PBSC infusion: given on Day 0

Drug: Thiotepa; Drug: Fludarabine; Drug: Busulfan; Procedure: PBSC infusion

Cohort 2: T2FluBu2 (high-intensity)

EXPERIMENTAL

Thiotepa: 5 mg/kg - administered on Day -5 prior to PBSC infusion Fludarabine: 40 mg/m2/day - administered on Day -4, Day -3, Day -2 and Day -1 prior to PBSC infusion Busulfan: 3.2 mg/kg/day IV - administered on Day -4 and Day -3 prior to PBSC infusion PBSC infusion: given on Day 0

Drug: Thiotepa; Drug: Fludarabine; Drug: Busulfan; Procedure: PBSC infusion

Interventions

Thiotepa DRUG

Thiotepa is an alkylating agent used in combination with other chemotherapy agents to treat cancer.

Also known as: Tepadina

Cohort 1: T1FluBu2 (low-intensity); Cohort 2: T2FluBu2 (high-intensity)

Fludarabine DRUG

Fludarabine is a chemotherapy drug used in the treatment of chronic lymphocytic leukemia. It acts at DNA polymerase alpha, ribonucleotide reductase and DNA primase, results in the inhibition of DNA synthesis, and destroys the cancer cells.

Cohort 1: T1FluBu2 (low-intensity); Cohort 2: T2FluBu2 (high-intensity)

Busulfan DRUG

Busulfan is a chemotherapy drug used in preparation for a stem cell transplant.

Cohort 1: T1FluBu2 (low-intensity); Cohort 2: T2FluBu2 (high-intensity)

PBSC infusion PROCEDURE

Peripheral Blood Stem Cell (PBSC) infusion is a medical procedure used to replace diseased or damaged stem cells in patients, particularly after cancer treatments.

Cohort 1: T1FluBu2 (low-intensity); Cohort 2: T2FluBu2 (high-intensity)

Eligibility Criteria

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

You may qualify if:

• Patients must be considered appropriate candidates for either the low- or high-intensity conditioning regimen for allogeneic hematopoietic stem cell transplantation based on the following age-related criteria:
• Age 50-70 years old or
• Age 18-49 and unfit for a conventional myeloablative conditioning regimen per the treating physician
• Patients have one of the following diagnoses:
• Acute lymphocytic leukemia (ALL) in first or subsequent morphological remission (\<5% marrow blasts by morphology).
• Acute myeloid leukemia (AML) in first or subsequent morphological remission (\<5% marrow blasts by morphology) with or without hematologic recovery.
• Other acute leukemia or related neoplasm (including but not limited to 'mixed phenotype' 'biphenotypic', 'acute undifferentiated' or 'ambiguous lineage' acute leukemia, blastic plasmacytoid dendritic cell neoplasm, lymphoblastic lymphoma, Burkitt leukemia/lymphoma, mast cell leukemia or chronic myeloid leukemia with blast crisis) in first or subsequent morphological remission (\<5% marrow blasts by morphology) with or without hematologic recovery.
• Myelodysplastic syndrome (MDS) with a history of excess blasts, with \>5% marrow blasts by morphology after receiving at least one cycle of treatment, including but not limited to hypomethylating agent, BCL-2 inhibitor, cytoreductive chemotherapy.
• High-risk myeloproliferative neoplasm (MPN) with no evidence of high-grade bone marrow fibrosis or massive splenomegaly at the time of enrollment.
• Patients with an 8/8 HLA-matched (HLA-A, B, C, DRB1) related or unrelated donor capable of donating peripheral blood stem cells (PBSC)
• Provision of signed and dated informed consent form
• Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception prior to study entry, during the course of the study, and until tacrolimus or other immunosuppressive therapy for GVHD is discontinued (whichever is later). An additional contraceptive method, such as a barrier method (e.g., condom), is required. In addition, men must agree not to donate sperm and women must agree not to donate eggs (ova, oocyte) for the purpose of reproduction during these same periods.
• Female subjects of childbearing potential must not be pregnant or breastfeeding at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria is met:
• Permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \> 45 years-of-age in the absence of other biological or physiological causes). Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff.

You may not qualify if:

• Subjects will be excluded from the study if they meet any of the following criteria.
• For high-intensity regimen:
• Poor performance status with Karnofsky Score \<70%
• Center for International Blood and Marrow Transplant Research (CIBMTR) hematopoietic cell transplant co-morbidity index (HCT-CI) score \>5
• Patients with active central nervous system (CNS) involvement refractory to intrathecal chemotherapy and/or standard craniospinal radiation.
• Patients who are positive for HIV-1, HIV-2, HTLV1 or HTLV2.
• Patients with uncontrolled infections for whom alloSCT is considered contraindicated by the consulting infectious disease physician.
• Patients with organ dysfunction, including:
• Renal insufficiency creatinine clearance \<45 ml/min/1.72m2 measured by 24-hr urine specimen
• Left ventricular ejection fraction \<45%
• Diffusing capacity of the lung for carbon monoxide (DLCO) corrected \<50% or FEV1 \<50%
• Liver function abnormality: total bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) \>5 times the upper limit of normal should be evaluated by a gastroenterologist. If a gastroenterologist considers that alloSCT is contraindicated, the patient will be excluded from the protocol.
• Patients who have received previous allogeneic transplantation.
• Patients with a life expectancy \<12 months due to co-existing diseases other than hematologic malignancies.
• Patients with any other significant medical conditions that would make them unsuitable for transplantation, as determined by the PI.

Sponsors & Collaborators

• Sawa Ito, MD: lead

Study Sites (1)

UMPC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Graft vs Host Disease

Interventions

Thiotepa; fludarabine; Busulfan

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Sawa M Ito, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amy Rogers, RN, BSN

CONTACT

412-623-4036; rodgera@upmc.edu

Linda Elias, RN, BSN

CONTACT

412-623-6037; eliaslj@upmc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine, Malignant Hematology and Medical Oncology

Study Record Dates

• First Submitted: April 27, 2026
• First Posted: May 4, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): November 1, 2030
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)