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Recurrent T-Cell Non-Hodgkin LymphomaPhase 1/2NCT07225985

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

A Phase 1/2 study testing Bendamustine, Pralatrexate and Bone Marrow Aspiration in people with Recurrent T-Cell Non-Hodgkin Lymphoma and Refractory T-Cell Non-Hodgkin Lymphoma, run by Fred Hutchinson Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Bendamustine, Pralatrexate and Bone Marrow Aspiration
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteUnited States
Study dates
27 Apr 2026to 15 Nov 2030
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 32Show fewer
  • 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
  • An 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
  • MATCHED UNRELATED DONOR: Donors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment. The recommended procedure for patients with 10 of 10 HLA allele level (phenotypic) match is to obtain panel reactive antibody (PRA) screens to class I and class II antigens for all patients before HCT. If the PRA shows > 10% activity, then flow cytometric or B and T cell cytotoxic cross matches should be obtained. The donor should be excluded if any of the cytotoxic cross match assays are positive. For those patients with an HLA Class I allele mismatch, flow cytometric or B and T cell cytotoxic cross matches should be obtained regardless of the PRA results. A positive anti-donor cytotoxic crossmatch is an absolute donor exclusion.
  • MATCHED UNRELATED DONOR: Patient and donor pairs homozygous at a mismatched allele in the graft rejection vector are considered a two-allele mismatch, i.e., the patient is A*0101 and the donor is A*0102, and this type of mismatch is not allowed.
  • MISMATCHED UNRELATED DONOR: HLA-matching must be based on results of high resolution typing at HLA-A, -B, -C, -DRB1, and -DQ
  • MISMATCHED UNRELATED DONOR: Mismatch for one HLA class I antigen with or without an additional mismatch for one HLA-class I allele but matched for HLA-DRB1 and HLA-DQ
  • MISMATCHED UNRELATED DONOR: Mismatched for two HLA class I alleles but matched for HLA-DRB1 and HLA-DQ
  • MISMATCHED UNRELATED DONOR: HLA class I HLA-A, -B, -C allele matched donors allowing for any one or two DRB1 and/or DQB1 antigen/allele mismatch
  • MISMATCHED UNRELATED DONOR: If the patient is homozygous at the mismatch HLA class I locus or II locus, the donor must be heterozygous at that locus and one allele must match the patient (i.e., patient is homozygous A*01:01 and donor is heterozygous A*01:01, A*02:01). This mismatch will be considered a one-antigen mismatch for rejection only
  • HAPLOIDENTICAL DONOR: Donors must be haploidentical relatives of the patients. Donor-recipient compatibility will be tested through HLA typing at high resolution for the HLA loci (-A, -B, -C, -DRB1, -DQB1). Donor and recipient should share at least 5/10 HLA loci
  • HAPLOIDENTICAL DONOR: Age ≥ 18 years
  • HAPLOIDENTICAL DONOR: Weight ≥ 40 kg
  • HAPLOIDENTICAL DONOR: Donor must meet the selection criteria as defined by the Foundation of the Accreditation of Cell Therapy (FACT) and will be screened per the American Association of Blood Banks (AABB) guidelines
  • HAPLOIDENTICAL DONOR: In case of more available haploidentical donors, selection criteria should include, in this order:
  • For cytomegalovirus (CMV) seronegative recipients, a CMV seronegative donor
  • Red blood cell compatibility
  • Red blood cell (RBC) cross match compatible
  • Minor ABO incompatibility
  • Major ABO incompatibility

Who cannot join

  • 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 lymphoid 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Lorenzo Iovino, MD, PhD contact

206-667-4475

liovino@fredhutch.org

United States1 site, 1 recruiting

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

    Lorenzo Iovino, MD, PhD, 206-667-4475, liovino@fredhutch.org

    Lorenzo Iovino, MD, PhD

    Recruiting

Other trials in United States

About this study

Official title: Pralatrexate and Bendamustine With 3 Gy TBI as a New Reduced Intensity Conditioning (RIC) Regimen for Allogeneic HCT for T-Cell Lymphoma Patients Who Are in Untreated R/R, or in Remission With MRD

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.

Read the detailed description

OUTLINE:

This is a phase I dose-escalation study of pralatrexate in combination with bendamustine and TBI followed by a phase II expansion study.

Patients receive pralatrexate intravenously (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 peripheral blood stem cell (PBSC) HCT on day 0. Patients also undergo echocardiography (ECHO) or multi-gated acquisition scan (MUGA) and lumbar puncture during screening, positron emission tomography-computed tomography (PET-CT), magnetic resonance imaging (MRI), bone marrow biopsy/aspiration, and blood sample collection throughout the study. In addition, patients may undergo chest X-rays as clinically indicated.

After completion of study treatment, patients are followed up at 6 and 9 months and at 1, 1.5 and 2 years.

Being tested
Bendamustine, Pralatrexate, Bone Marrow Aspiration, Bone Marrow Biopsy, Chest Radiography
Medical subject headings
Lymphoma, T-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BendamustineDrug

    Also called SDX 105, SDX-105, SDX105

    Given IV

  • PralatrexateDrug

    Also called 10-propargyl-10-deazaaminopterin, Difolta, Folotyn, PDX

    Given IV

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow biopsy/aspiration

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy/aspiration

  • Chest RadiographyProcedure or surgery

    Also called Chest X-ray

    Undergo chest X-rays

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo PET-CT

  • Echocardiography TestProcedure or surgery

    Also called EC, Echocardiography

    Undergo ECHO

  • Lumbar PunctureProcedure or surgery

    Also called LP, Spinal Tap

    Undergo lumbar puncture

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Multigated Acquisition ScanProcedure or surgery

    Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan

    Undergo MUGA

  • Peripheral Blood Stem Cell TransplantationProcedure or surgery

    Also called PBPC transplantation, PBSCT, Peripheral Blood, Peripheral Blood Progenitor Cell Transplantation

    Undergo PBSC HCT

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET-CT

  • Questionnaire AdministrationOther

    Ancillary studies

  • Total-Body IrradiationRadiation

    Also called SCT_TBI, TBI, Total Body Irradiation, Whole Body

    Undergo TBI

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

Study groups in NCT07225985
Study groupRoleWhat they receive
Treatment (pralatrexate, bendamustine, TBI, PBSC HCT)ExperimentalPatients 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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%.

    Measured: Up to 2 years post-transplant

Secondary outcomes (10)

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

    Measured: Up to day 100 post-transplant

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

    Group comparisons will be performed using Gray's test, and multivariable analyses will be conducted using cause-specific Cox model to assess the effect of covariates. The cumulative incidence of acute will be estimated using the cumulative incidence function.

    Measured: Up to day 100 post-transplant

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

    Group comparisons will be performed using Gray's test, and multivariable analyses will be conducted using cause-specific Cox model to assess the effect of covariates. The cumulative incidence of acute will be estimated using the cumulative incidence function.

    Measured: Up to day 100 post-transplant

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

    Group comparisons will be performed using Gray's test, and multivariable analyses will be conducted using cause-specific Cox model to assess the effect of covariates. Group comparisons will be performed using Gray's test, and multivariable analyses will be conducted using cause-specific Cox model to assess the effect of covariates. The cumulative incidence will be estimated using the cumulative incidence function.

    Measured: At 1 year post-transplant

  5. Disease response rate (Phase 2)

    Proportion and counts will be calculated with an exact 95% confidence intervals.

    Measured: At day 100 post-transplant

  6. Duration of remission from response until documented relapse or progression (Phase 2)

    Measured: From response until documented relapse or progression, per disease-specific response criteria up to 2 years post-transplant

  7. Rates of donor chimerism ≥ 90% in peripheral blood CD3+ and CD33+ cell lines

    Proportion and counts will be calculated with an exact 95% confidence intervals. Donor chimerism will be summarized by the observed levels and levels categorized as ≥ 95%, 50% - 94%, 5% - 49%, or < 5%.

    Measured: Up to day 80 post-transplant

  8. Disease-free survival (Phase 2)

    Will be defined as the proportion of patients who are alive and free of disease. The Kaplan-Meier method will be used to estimate the median with 95% confidence intervals. Log-rank test will be used for group comparison. Proportion and counts will be calculated with an exact 95% confidence intervals.

    Measured: From day 0 (date of graft infusion) to the first of: Relapse/progression of the underlying disease, or death from any cause, assessed up to 1 year post-transplant

  9. NRM (Phase 2)

    Measured: Up to day 100 post-transplant

  10. Overall survival (Phase 2)

    The Kaplan-Meier method will be used to estimate the median with 95% confidence intervals. Log-rank test will be used for group comparison.

    Measured: Up to 2 years post-transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Nov 2025
  2. Study start27 Apr 2026
  3. Primary completion30 Sep 2030 (estimated)
  4. Study completion15 Nov 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07225985
Sponsor's protocol ID
RG1125830
Other IDs
NCI-2025-07661, FHIRB0021079
Status last verified
May 2026
First submitted
5 Nov 2025
Last updated
11 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Bendamustine, Pralatrexate and Bone Marrow Aspiration in people with Recurrent T-Cell Non-Hodgkin Lymphoma and Refractory T-Cell Non-Hodgkin Lymphoma, run by Fred Hutchinson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 11 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Lorenzo Iovino, MD, PhD (206-667-4475, liovino@fredhutch.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence and severity of treatment-emergent adverse events and treatment-emergent serious adverse events (Phase 1) (time frame: From pralatrexate dosing on day -6 to 28 days post-transplant). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07225985.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2026.

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