Inclusion Criteria:

1. Diagnosis will be per the Revised European American Lymphoma (REAL) World Health Organization (WHO) disease classification. Phase 1: Histologically or cytologically confirmed lymphoproliferative malignancy. Patients with either Hodgkin's disease or non-Hodgkin's lymphoma are eligible, with the exception of patients with particular B-cell lymphomas, as per exclusion criterion #1.

   Phase 2a: Histologically/cytologically confirmed PTCL or B-cell lymphoma (with the exceptions per exclusion criterion #1):

2. Documented progression of disease after at least 1 prior treatment. Any number of prior therapies will be allowed. The patient should have clearly progressed after their last prior treatment regimen. The patient has recovered from the toxic effects of prior therapy. Patients treated with a Food and Drug Administration (FDA)-approved monoclonal antibody therapy may be enrolled regardless of the time frame after the therapy if they have progression of disease.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
4. At least 18 years of age.

5. Adequate hematological, hepatic, and renal function as defined by:

   absolute neutrophil count (ANC) ≥ 1000/μL, platelet count ≥ 100,000/μL, total bilirubin ≤ 1.5 mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN) (AST/ALT ≤ 5 × ULN if documented hepatic involvement with lymphoma), creatinine

   ≤ 1.5 mg/dL or calculated creatinine clearance ≥ 50 mL/min.

6. Methylmalonic acid (MMA) < 200 nmol/L and homocysteine (Hcy) < 10 μmol/L or the patient has been on a regimen of 1 mg PO QD of folic acid for at least 10 days prior to planned start of pralatrexate and has received 1 mg IM of vitamin B12 within 10 weeks of the planned start of pralatrexate.
7. Women of childbearing potential must agree to practice a medically acceptable contraceptive regimen from study treatment initiation until at least 30 days after the last administration of pralatrexate and must have a negative serum pregnancy test within 14 days prior to the first day of study treatment. Patients who are postmenopausal for at least 1 year (defined as > 12 months since last menses) or are surgically sterilized do not require this test.
8. Men who are not surgically sterile must agree to practice a medically acceptable contraceptive regimen from study treatment initiation until at least 90 days after the last administration of pralatrexate.
9. Given written informed consent (IC).

Exclusion Criteria:

1. Phase 1

   B-cell:

   1. Lymphoplasmacytic lymphoma (± Waldenström's macroglobulinemia)
   2. Plasma cell myeloma/plasmacytoma
   3. Hairy cell leukemia Phase 2a

   PTCL:

   1. Precursor T/NK neoplasms, with the exception of blastic NK lymphoma
   2. T-cell prolymphocytic leukemia (T-PLL)
   3. T-cell large granular lymphocytic leukemia
   4. Mycosis fungoides, other than transformed mycosis fungoides
   5. Sézary syndrome
   6. Primary cutaneous CD30+ disorders: Anaplastic large cell lymphoma and lymphomatoid papulosis

   B-cell:

   1. Lymphoplasmacytic lymphoma (± Waldenström's macroglobulinemia)
   2. Plasma cell myeloma/plasmacytoma
   3. Hairy cell leukemia
2. Relapsed Hodgkin's disease or diffuse large B-cell lymphoma who are candidates for high dose therapy and autologous stem cell transplantation and for whom high dose therapy and autologous stem cell transplantation is a standard curative option.
3. Active concurrent malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix). If there is a history of prior malignancy, the patient must be disease-free for ≥ 5 years.
4. Congestive heart failure Class III/IV according to the New York Heart Association (NYHA) Functional Classification.
5. Uncontrolled hypertension.
6. Human immunodeficiency virus (HIV)-positive diagnosis and is receiving combination anti-retroviral therapy.
7. Central nervous system (CNS) disease.
8. Undergone an allogeneic stem cell transplant.
9. Relapsed < 100 days from time of an autologous stem cell transplant. Patients with disease refractory to peripheral blood stem cell transplant (PBSCT) or who have relapsed < 100 days from the time of transplant are not eligible.
10. Active uncontrolled infection, underlying medical condition including unstable cardiac disease, or other serious illness that would impair the ability of the patient to receive protocol treatment.
11. Major surgery within 2 weeks of planned start of treatment.
12. Receipt of any conventional chemotherapy or radiation therapy (RT) (encompassing a substantial [> 10%] amount of bone marrow) within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to study treatment or planned use during the course of the study.
13. Receipt of systemic corticosteroids within 7 days of study treatment, unless patient has been taking a continuous dose of no more than 10 mg/day of prednisone for at least 1 month.
14. Use of any investigational drugs, biologics, or devices within 4 weeks prior to study treatment or planned use during the course of the study.
15. Received a monoclonal antibody within 3 months without evidence of progression.
16. Previous exposure to pralatrexate if it was discontinued due to treatment-related toxicity.
17. Previous exposure to gemcitabine if it was discontinued due to treatment-related toxicity.