A Study to Evaluate VSV-hIFNbeta-NIS to Treat Patients with Relapsed/Refractory Multiple Myleoma, Acute Myeloid Leukemia, or T-cell Lymphoma

Overview

About this study

This phase I trial studies the best dose and side effects of recombinant vesicular stomatitis virus carrying the human NIS and IFN beta genes (VSV-hIFNbeta-sodium iodide symporter [NIS]) in treating patients with multiple myeloma, acute myeloid leukemia, or T-cell lymphoma that has come back or does not respond to treatment. A virus, called VSV-hIFNbeta-NIS, which has been changed in a certain way, may be able to kill cancer cells without damaging normal cells.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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.

 

 

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Martha Lacy, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Sikander Ailawadhi, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Javier Munoz, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20304531

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