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