Pralatrexate With Bendamustine and Total-Body Irradiation Followed by Donor Stem Cell Transplant for the Treatment of Relapsed or Refractory T-Cell Non-Hodgkin Lymphoma

NCT07225985 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: RG1125830NCI-2025-07661FHIRB0021079
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects and best dose of pralatrexate in combination with bendamustine and total-body irradiation (TBI) followed by a donor stem cell transplant in treating patients with T-cell non-Hodgkin lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Pralatrexate may block the growth of cancer cells and cause them to die. It is a type of dihydrofolate reductase (DHFR) inhibitor. Bendamustine may damage the DNA in cancer cells and cause them to die. It is a type of alkylating agent and a type of antimetabolite. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. TBI is a type of radiation therapy that is given to the entire body. Giving pralatrexate with bendamustine and TBI before a donor stem cell transplant may help kill cancer cells in the body and help make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow.

Conditions

Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (2)

• Incidence and severity of treatment-emergent adverse events and treatment-emergent serious adverse events (Phase 1)

  In addition, clinically significant laboratory abnormalities, changes in vital signs, and changes in physical examination following allogeneic hematopoietic cell transplantation (allo-HCT). Will be graded according to Common Terminology Criteria for Adverse Events version 5.0. Will be summarized by grades and put in different tables by dose.

  From pralatrexate dosing on day -6 to 28 days post-transplant

• Proportion of enrolled patients with T-cell non-Hodgkin lymphoma who successfully proceed to allogeneic-hematopoietic cell transplant (HCT) (Phase 2)

  Will compare it with the historical rate of 31%.

  Up to 2 years post-transplant

Secondary Outcomes (10)

• Non-relapse mortality (NRM) (Phase 1)

  Up to day 100 post-transplant

• Incidence and severity of grade II-IV acute graft-versus-host disease (GVHD) (Phase 2)

  Up to day 100 post-transplant

• Incidence and severity of grade III-IV acute GVHD (Phase 2)

  Up to day 100 post-transplant

• Incidence and severity of chronic GVHD requiring systemic immunosuppressive therapy (Phase 2)

  At 1 year post-transplant

• Disease response rate (Phase 2)

  At day 100 post-transplant

Study Arms (1)

Treatment (pralatrexate, bendamustine, TBI, PBSC HCT)

EXPERIMENTAL

Patients receive pralatrexate IV over 3-5 minutes on day -6, bendamustine IV over 60 minutes on days -5, -4, and -3, and TBI on day -1 or 0. Patients then undergo PBSC HCT on day 0. Patients also undergo ECHO or MUGA and lumbar puncture during screening, PET-CT, MRI, bone marrow biopsy/aspiration, and blood sample collection throughout the study. In addition, patients may undergo chest X-rays as clinically indicated.

Drug: Bendamustine; Drug: Pralatrexate; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Chest Radiography; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Procedure: Peripheral Blood Stem Cell Transplantation; Procedure: Positron Emission Tomography; Other: Questionnaire Administration; Radiation: Total-Body Irradiation; Procedure: Biospecimen Collection

Interventions

Bendamustine DRUG

Given IV

Also known as: SDX 105, SDX-105, SDX105

Treatment (pralatrexate, bendamustine, TBI, PBSC HCT)

Pralatrexate DRUG

Given IV

Also known as: 10-propargyl-10-deazaaminopterin, Difolta, Folotyn, PDX

Treatment (pralatrexate, bendamustine, TBI, PBSC HCT)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy/aspiration

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (pralatrexate, bendamustine, TBI, PBSC HCT)

Computed Tomography PROCEDURE

Undergo PET-CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (pralatrexate, bendamustine, TBI, PBSC HCT)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Treatment (pralatrexate, bendamustine, TBI, PBSC HCT)

Lumbar Puncture PROCEDURE

Undergo lumbar puncture

Also known as: LP, Spinal Tap

Treatment (pralatrexate, bendamustine, TBI, PBSC HCT)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo PBSC HCT

Also known as: PBPC transplantation, PBSCT, Peripheral Blood, Peripheral Blood Progenitor Cell Transplantation, PERIPHERAL BLOOD STEM CELL TRANSPLANT, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation

Treatment (pralatrexate, bendamustine, TBI, PBSC HCT)

Positron Emission Tomography PROCEDURE

Undergo PET-CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Treatment (pralatrexate, bendamustine, TBI, PBSC HCT)

Questionnaire Administration OTHER

Ancillary studies

Treatment (pralatrexate, bendamustine, TBI, PBSC HCT)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: SCT_TBI, TBI, Total Body Irradiation, Whole Body, Whole Body Irradiation, Whole-Body Irradiation

Treatment (pralatrexate, bendamustine, TBI, PBSC HCT)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow biopsy/aspiration

Treatment (pralatrexate, bendamustine, TBI, PBSC HCT)

Chest Radiography PROCEDURE

Undergo chest X-rays

Also known as: Chest X-ray

Treatment (pralatrexate, bendamustine, TBI, PBSC HCT)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (pralatrexate, bendamustine, TBI, PBSC HCT)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Treatment (pralatrexate, bendamustine, TBI, PBSC HCT)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (pralatrexate, bendamustine, TBI, PBSC HCT)

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years with an HCT-Comorbidity Index (CI) ≤ 5 for patients over 60 years
• T-cell non-Hodgkin lymphoma (T-NHL) (2022 World Health Organization \[WHO\] criteria) including primary cutaneous T-NHL that is in untreated or unsuccessfully treated first or subsequent relapse. Patients in morphologic remission (i.e. \< 5% blasts in the bone marrow, if involved) but evidence of minimal residual disease (MRD) by positron emission tomography-computed tomography (PET-CT), multiparameter flow cytometry, cytogenetics/fluorescence in situ hybridization (FISH), or molecular means will be eligible for trial participation
• The use of bridging chemotherapy prior to initiation of study treatment is allowed. Patients with symptoms/signs of hyperleukocytosis, white blood cells (WBC) \> 100,000/µL, or with concern for other complications of high tumor burden of high tumor dynamics (e.g. disseminated intravascular coagulation) can be treated with leukapheresis or may receive a cycle of salvage chemotherapy prior to start of study treatment
• Karnofsky score ≥ 70; Eastern Cooperative Oncology Group (ECOG) 0-1
• Adequate cardiac function defined as absence of decompensated congestive heart failure and/or uncontrolled arrhythmia and left ventricular ejection fraction ≥ 45%
• Bilirubin ≤ 2.5 x institutional upper limit of normal unless elevation is thought to be due to hepatic infiltration by lymphoma, Gilbert's syndrome, or hemolysis
• Adequate pulmonary function defined as absence of oxygen (O2) requirements and either diffusion capacity of the lung for carbon monoxide (DLCO) corrected ≥ 70%mmHg or DLCO corrected 60-69%mmHg and partial pressure of oxygen (pO2) ≥ 70mmHg
• Creatinine clearance ≥ 60 mL/min
• Prior autologous HCT is permissible if relapse occurred \> 6 months after HCT
• A human leukocyte antigen (HLA)-matched sibling/unrelated donor mismatched unrelated donor or haploidentical donor for collection of stimulated peripheral blood stem cells must be identified and readily available
• If the patient has received pralatrexate or bendamustine before and has been sensitive to this regimen, defined as MRD negative complete response (CR) immediately after receiving the treatment and which lasts ≥ 1 year, eligibility will be determined on a case-by-case basis by the study principal investigator (PI)
• Ability to understand and sign a written informed consent document (or legal representative)
• RELATED DONOR: Related to the patient and genotypically or phenotypically identical for HLA-A, B, C, DRB1 and DQB1. Phenotypic identity must be confirmed by high-resolution typing
• MATCHED UNRELATED DONOR: Matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing; OR
• MATCHED UNRELATED DONOR: Mismatched for a single allele without antigen mismatching at HLA-A, B, or C as defined by high resolution typing but otherwise matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing

You may not qualify if:

• Active central nervous system (CNS) disease
• Concomitant illness associated with a likely survival of \< 1 year
• Active systemic fungal, bacterial, viral, or other infection, unless disease is under treatment with antimicrobials and/or controlled or stable. Patients with fever thought to be likely secondary to myeloid malignancy are eligible
• Known hypersensitivity or contraindication to any study drug used in this trial
• Pregnancy or lactation
• Concurrent treatment with any other approved or investigational anti-lymphoma agent at the time of starting conditioning
• HAPLOIDENTICAL DONOR: Since detection of anti-donor-specific antibodies (anti-DSA) is associated with higher graft rejection rate, patients will be screened for anti-DSA pre-transplant. Patient with DSA mean fluorescent intensity (MFI) \< 5000 after desensitization treatment, will be considered eligible to participate in the study

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, T-Cell

Interventions

Bendamustine Hydrochloride; 10-propargyl-10-deazaaminopterin; Biopsy; X-Rays; Spinal Puncture; Magnetic Resonance Spectroscopy; Peripheral Blood Stem Cell Transplantation; Whole-Body Irradiation; Specimen Handling

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Spectrum Analysis; Chemistry Techniques, Analytical; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Radiotherapy

Study Officials

• Lorenzo Iovino, MD, PhD

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lorenzo Iovino, MD, PhD

CONTACT

206-667-4475; liovino@fredhutch.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2025
• First Posted: November 10, 2025
• Study Start: April 27, 2026
• Primary Completion (Estimated): September 30, 2030
• Study Completion (Estimated): November 15, 2030
• Last Updated: April 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)