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.
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
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
Single group
Bendamustine
DrugGiven IV
Pralatrexate
DrugGiven IV
Bone Marrow Aspiration
Procedure/SurgeryUndergo bone marrow biopsy/aspiration
Bone Marrow Biopsy
Procedure/SurgeryUndergo bone marrow biopsy/aspiration
Chest Radiography
Procedure/SurgeryUndergo chest X-rays
Computed Tomography
Procedure/SurgeryUndergo PET-CT
Echocardiography Test
Procedure/SurgeryUndergo ECHO
Lumbar Puncture
Procedure/SurgeryUndergo lumbar puncture
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Multigated Acquisition Scan
Procedure/SurgeryUndergo MUGA
Peripheral Blood Stem Cell Transplantation
Procedure/SurgeryUndergo PBSC HCT
Positron Emission Tomography
Procedure/SurgeryUndergo PET-CT
Questionnaire Administration
Other interventionAncillary studies
Total-Body Irradiation
RadiationUndergo TBI
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
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.
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%.
Non-relapse mortality (NRM) (Phase 1)
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.
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.
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.
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