Inclusion Criteria:​​​​​​

• Age ≥ 18 years.
• Relapsed or refractory:
  • Groups A, B, or C: Multiple myeloma (MM) previously treated with an IMID, a proteosome inhibitor and an alkylating agent; OR
  • Groups A or B: Acute myeloid leukemia (AML), excluding acute promyelocytic leukemia (PML-RARA rearranged- AML-M3); either primary refractory or relapsed/refractory disease after at least two front line chemotherapy regimens (note: induction and consolidation chemotherapy is considered one line of therapy). Diagnosis based on 2008 WHO criteria; OR
  • Groups A, B, or C: Relapsed T-cell lymphoma (TCL) or the following types: peripheral T-cell lymphoma-NOS (PTCL-NOS); angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell (ALCL), and cutaneous TCL (CTCL) of mycosis fungoides (MF). Patients should have failed standard therapy and in the case of PTCL-NOS, AITL, and ALCL either have failed or be ineligible for high-dose therapy with autologous stem cell transplant.
• All diseases/All Groups: The following laboratory values obtained ≤ 14 days prior to registration:
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST);
  • ≤ 2 times upper limit of normal (ULN);
  • Creatinine ≤ 2.0 mg/dL;
  • Direct bilirubin ≤ 1.5 x ULN;
  • INR/PT and aPTT ≤ 1.5 x ULN.
• If baseline liver disease, Child Pugh score not exceeding Class A.
• Negative pregnancy test for persons of child-bearing potential.

For multiple myeloma only

• Measurable disease of multiple myeloma as defined by at least ONE of the following:
  • Serum monoclonal protein ≥ 1.0 g/dL by protein electrophoresis;
  • ≥ 200 mg of monoclonal protein in the urine on 24-hour electrophoresis;
  • Serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio.
• The following laboratory values obtained ≤ 14 days prior to registration:
  • ANC ≥ 1000/μL;
  • PLT ≥ 100,000/μL;
  • Hemoglobin ≥ 8.5 g/dl.

For AML only

• The following laboratory values obtained ≤ 14 days prior to registration:
• • No ANC restriction;
  • PLT ≥ 10,000/μL (transfusion to get platelets ≥ 10,000 is allowed);
  • Hemoglobin ≥ 7.5 g/dl.
• Absence of uncompensated disseminated intravascular coagulation (DIC- as diagnosed by standard ISTH criteria).

For TCL only

• The following laboratory values obtained ≤ 14 days prior to registration:
• • ANC ≥1,000/μL;
  • PLT ≥ 100,000/μL;
  • Hemoglobin ≥ 8.5 g/dl.
• Measurable disease by CT or MRI:
  • Must have at least one lesion that has a single diameter of > 2 cm or tumor cells in the blood > 5 x10^9/L.
  • NOTE: Skin lesions can be used if the area is > 2 cm in at least one diameter and photographed with a ruler and the images are available in the medical record.
• Absence of active CNS involvement.
  • NOTE: Pre-enrollment lumbar puncture not mandatory.
• Ability to provide written informed consent.
• Willingness to return to Mayo Clinic for follow-up.
• Life expectancy ≥ 12 weeks.
• ECOG performance status (PS) 0, 1, or 2.
• Willing to provide mandatory biological specimens for research purposes.

Exclusion Criteria:

• Availability of and patient acceptance of curative therapy.
• Uncontrolled infection.
• Active tuberculosis or hepatitis, or history of hepatitis B or C, or chronic hepatitis.
• Any of the following prior therapies:
  • Chemotherapy (IMIDs, alkylating agents, proteosome inhibitors) ≤ 2 weeks prior to registration;
  • Immunotherapy (monoclonal antibodies) ≤ 4 weeks prior to registration;
  • Experimental agent in case of AML or TCL within 4 half-lives of the last dose of the agent;
  • New York Heart Association classification III or IV, known symptomatic coronary artery disease, or symptoms of coronary artery disease on systems review, or known cardiac arrhythmias (atrial fibrillation or SVT).
• Active CNS disorder or seizure disorder or known CNS disease or neurologic symptomatology. In case of AML active CNS involvement as detected by lumbar puncture or neuro-imaging (only to be done if clinically indicated).
• HIV positive test result or other immunodeficiency or immunosuppression.
• Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (used for a non-FDA approved indication and in the context of a research investigation).
  • NOTE: In AML, the concurrent use of hydroxyurea to help control proliferative counts is allowed throughout the treatment protocol.
  • NOTE: In TCL, patients may use topical emollients or corticosteroids, acetic acid soaks, etc. to control pruritis and prevent infection. No topical chemotherapy is allowed (no topical nitrogen mustard).
• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
  • Pregnant women or women of reproductive ability who are unwilling to use effective contraception;
  • Nursing women;
  • Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 4 weeks after stopping treatment.
• Prior allogeneic bone marrow transplant.

AML only:  Current disseminated intravascular coagulopathy (DIC).

• Additional exclusion criteria for Group A (low tumor burden) ONLY:

AML only:  Acute promyelocytic leukemia (PML-RARA rearranged- AML-M3).

AML only

• AML with > 30% circulating blasts and > 50% bone marrow blasts.
• Multiple myeloma only: ≥ 15% plasmas cells or plasmacytoma > 5cm in largest diameter.

TCL only:  Any mass ≥ 5cm.

• Additional exclusion criteria for Group C (combination with cyclophosphamide) ONLY:
  • Diagnosis of AML.