VSV-hIFNbeta-NIS With or Without Ruxolitinib Phosphate in Treating Patients With Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia, Lymphomas, or Histiocytic/Dendritic Cell Neoplasms

Age ≥18 years

Relapsed or refractory disease as follows:

Groups A, B, or C, or D: Multiple myeloma (MM) previously treated with an IMID, a proteosome inhibitor, and an alkylating agent.
Groups A, B, or C only: Relapsed peripheral T-cell lymphoma (PTCL) orf the following histologies: peripheral T-cell lymphoma-NOS (PTCLNOS); angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell (ALCL), and 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
Group B and C only: B-cell lymphoma (other than Burkitt's lymphoma), or histiocytic/dendritic cell neoplasms (HCN) at any stage
Group E only: Relapsed peripheral T-cell lymphoma (PTCL) of the following histologies: peripheral T-cell lymphoma-NOS (PTCL-NOS); anaplastic large cell (ALCL), and mycosis fungoides (MF)
Group F only: Expansion Cohort for B-cell lymphoma (other than Burkitt's lymphoma) with low tumor burden

c)f) Group G only: Expansion Cohort for peripheral T cell lymphoma (PTCL) with low tumor burden

All diseases/All Groups: The following laboratory values obtained ≤15 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 OR if patient is receiving anticoagulant therapy, then INR or aPTT is within target range of therapy
If baseline liver disease, Child Pugh score not exceeding Class A (see Appendix III)
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/BCL only:

The following laboratory values obtained ≤14 days prior to registration

ANC ≥1,000/μL
PLT ≥100,000/μL
Hemoglobin ≥8.58.0 g/dl
Measurable disease by CT or MRI:

Must have at least one lesion that has a single diameter of >2 ≥1.5 cm or tumor cells in the blood >5 x109/L.

NOTE: Skin lesions can be used if the area is >2cm ≥1.5 cm in at least one diameter and photographed with a ruler and the images are available in the medical record.

For HCN only:

The following laboratory values obtained ≤15 days prior to registration

• ANC ≥1,000/μL

PLT ≥100,000/μL
Hemoglobin ≥8.0 g/dl
Measurable disease by CT or MRI:

Must have at least one lesion that has a single diameter of ≥1.5 cm or tumor cells in the blood >5 x109/L.

NOTE: Skin lesions can be used if the area is ≥1.5 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 (see Appendix I).
Willing to provide mandatory biological specimens for research purposes (See Section 14.0).

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) (Appendix II).
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.

AML only: Current disseminated intravascular coagulopathy (DIC).
Additional exclusion criteria for Group A (low tumor burden) ONLY:
Diagnosis of AML AML
Multiple myeloma only: ≥>125% plasmas cells or plasmacytoma >5cm in largest diameter
Lymphoma or HCN only: Any mass >5cm
Diagnosis of Burkitt's lymphoma

Additional exclusion for Groups D and E (combination with ipilimumab and nivolumab) ONLY:

- Diagnosis of AML

Diagnosis of AITL
Hypersensitivity to ipilimumab or its excipients Additional exclusion for Group F (BCL Expansion Cohort) ONLY
Diagnosis of Burkitt's lymphoma

Additional exclusion criteria for Group G (PTCL Expansion Cohort) ONLY:

Diagnosis of cutaneous TCL