Clinical Trial: NCT03017820 - My Cancer Genome

NCT03017820

Description:

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]) with or without ruxolitinib phosphate 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. Ruxolitinib phosphate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving VSV-hIFNbeta-NIS and ruxolitinib phosphate may work better at treating multiple myeloma, acute myeloid leukemia and T-cell lymphoma.

Related Conditions:

Acute Myeloid Leukemia
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-Cell Lymphoma
Multiple Myeloma
Peripheral T-Cell Lymphoma, Not Otherwise Specified
Primary Cutaneous T-Cell Non-Hodgkin Lymphoma

Recruiting Status:

Recruiting

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT03017820

Trial Eligibility

Document

Title

Brief Title: VSV-hIFNbeta-NIS With or Without Ruxolitinib Phosphate in Treating Patients With Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia, or T-cell Lymphoma
Official Title: Phase I Trial of Systemic Administration of Vesicular Stomatitis Virus Genetically Engineered to Express NIS and Human Interferon, in Patients With Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia, and T-Cell Neoplasms

Clinical Trial IDs

ORG STUDY ID: MC1684
SECONDARY ID: NCI-2017-00049
SECONDARY ID: MC1684
SECONDARY ID: P30CA015083
NCT ID: NCT03017820

Conditions

Myelodysplastic Syndrome
Previously Treated Myelodysplastic Syndrome
Recurrent Adult Acute Myeloid Leukemia
Recurrent Anaplastic Large Cell Lymphoma
Recurrent Angioimmunoblastic T-Cell Lymphoma
Recurrent Mycosis Fungoides
Recurrent Plasma Cell Myeloma
Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma
Recurrent T-Cell Non-Hodgkin Lymphoma
Refractory Acute Myeloid Leukemia
Refractory Anaplastic Large Cell Lymphoma
Refractory Angioimmunoblastic T-Cell Lymphoma
Refractory Mycosis Fungoides
Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified
Refractory Plasma Cell Myeloma
Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma
Refractory T-Cell Non-Hodgkin Lymphoma

Interventions

Drug	Synonyms	Arms
Cyclophosphamide	(-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719	Group C (VSV-IFNbeta-NIS, ruxolitinib, cyclophosphamide)
Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter	Oncolytic VSV-hIFNbeta-NIS, Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter, Voyager-V1, VSV-expressing hIFNb and NIS, VSV-hIFNb-NIS, VSV-hIFNbeta-NIS, VV1	Group A (VSV-IFNbeta-NIS)
Ruxolitinib Phosphate	INCB-18424 Phosphate, Jakafi	Group B (VSV-IFNbeta-NIS, ruxolitinib)

Purpose

Detailed Description

      PRIMARY OBJECTIVE:

      I. To determine the maximum tolerated dose (MTD) of VSV-hIFNbeta-NIS in different treatment
      regimens (alone [group A] and in combination with ruxolitinib phosphate [ruxolitinib] [group
      B]) in patients with relapsed/refractory multiple myeloma, acute myeloid leukemia, or T-cell
      lymphoma and in combination with ruxolitinib and cyclophosphamide (group C) in
      relapsed/refractory multiple myeloma patients.

      SECONDARY OBJECTIVES:

      I. To determine the safety profile of VSV-hIFNbeta-NIS (alone and in combination with
      ruxolitinib).

      II. To estimate clinical response rate of VSV-hIFNbeta-NIS (alone and in combination with
      ruxolitinib) in patients with relapsed/refractory multiple myeloma, acute myeloid leukemia,
      or T-cell lymphoma overall and by disease type.

      III. To estimate progression-free and overall survival of VSV-hIFNbeta-NIS (alone and in
      combination with ruxolitinib) in patients with relapsed/refractory multiple myeloma, acute
      myeloid leukemia, or T-cell lymphoma overall and by disease type.

      CORRELATIVE OBJECTIVES:

      I. To determine the time course of viral gene expression and virus elimination, and the
      biodistribution of virally infected cells at various times points after infection with
      VSV-hIFNbeta-NIS using planar and single photon emission computed tomography (SPECT)/computed
      tomography (CT) imaging.

      II. To assess virus replication, viremia, viral shedding in urine and respiratory secretions,
      and virus persistence after systemic administration of VSV-hIFNbeta-NIS.

      III. To characterize the pharmacodynamics (PD) of VSV-IFNbeta-NIS by way of measuring serum
      interferon-beta and also vesicular stomatitis virus (VSV)-real time (RT)-polymerase chain
      reaction (PCR) of VSV-IFNbeta-NIS.

      IV. Assess CD8+ T cell (both general and VSV-IFNbeta-NIS specific) and natural killer (NK)
      cell responses.

      V. Gene expression analysis pre- and post-virotherapy. VI. Assess presence of VSV in tumor
      and normal tissues subsequent to administration of intravenous (IV) VSV-IFNbeta-NIS.

      VII. To identify the best dose of VSV-hIFNbeta-NIS in the regimen being evaluated based on
      activity observed in the correlative measures described above in those dose levels identified
      as tolerable.

      OUTLINE: This is a dose escalation study of VSV-IFNbeta-NIS. Patients are assigned to 1 of 3
      groups.

      GROUP A: Patients receive VSV-IFNbeta-NIS intravenously (IV) over 30 minutes on day 1.
      Patients undergo SPECT/CT scans at baseline, and at days 3 and 8 after VSV-IFNbeta-NIS
      infusion.

      GROUP B: Patients receive VSV-IFNbeta-NIS IV over 30 minutes on day 1 and ruxolitinib
      phosphate orally (PO) twice daily (BID) on days -1 to 9. Patients undergo SPECT/CT scans at
      baseline, and at days 3 and 8 after VSV-IFNbeta-NIS infusion.

      GROUP C: Patients receive VSV-IFNbeta-NIS IV over 30 minutes on day 1 and ruxolitinib
      phosphate PO BID on days -1 to 9. Patients also receive cyclophosphamide IV over 2 hours on
      day 2. Patients undergo SPECT/CT scans at baseline, and at days 3 and 8 after VSV-IFNbeta-NIS
      infusion.

      After completion of study treatment, patients are followed up for 28 days, and then every 3
      months for up to 1 year or until progressive disease, then every 6 months for 1 year.

Trial Arms

Name	Type	Description	Interventions
Group A (VSV-IFNbeta-NIS)	Experimental	Patients receive VSV-IFNbeta-NIS IV over 30 minutes on day 1. Patients undergo SPECT/CT scans at baseline, and at days 3 and 8 after VSV-IFNbeta-NIS infusion.	Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter
Group B (VSV-IFNbeta-NIS, ruxolitinib)	Experimental	Patients receive VSV-IFNbeta-NIS IV over 30 minutes on day 1 and ruxolitinib phosphate PO BID on days -1 to 9. Patients undergo SPECT/CT scans at baseline, and at days 3 and 8 after VSV-IFNbeta-NIS infusion.	Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter Ruxolitinib Phosphate
Group C (VSV-IFNbeta-NIS, ruxolitinib, cyclophosphamide)	Experimental	Patients receive VSV-IFNbeta-NIS IV over 30 minutes on day 1 and ruxolitinib phosphate PO BID on days -1 to 9. Patients also receive cyclophosphamide IV over 2 hours on day 2. Patients undergo SPECT/CT scans at baseline, and at days 3 and 8 after VSV-IFNbeta-NIS infusion.	Cyclophosphamide Recombinant Vesicular Stomatitis Virus-expressing Human Interferon Beta and Sodium-Iodide Symporter Ruxolitinib Phosphate

Eligibility Criteria

        Inclusion Criteria:

          -  Relapsed or refractory:

               -  Groups A, B, or C: Multiple myeloma (MM) previously treated with an
                  immunomodulatory drug (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 World Health Organization (WHO) criteria; OR

               -  Groups A, B, or C: Relapsed T-cell lymphoma (TCL) or the following types:
                  peripheral T-cell lymphoma-not otherwise specified (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

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2 times upper
             limit of normal (ULN) (obtained =< 14 days prior to registration)

          -  Creatinine =< 2.0 mg/dL (obtained =< 14 days prior to registration)

          -  Direct bilirubin =< 1.5 x ULN (obtained =< 14 days prior to registration)

          -  International normalized ratio (INR)/prothrombin time (PT) and activated partial
             thromboplastin time (aPTT) =< 1.5 x ULN (obtained =< 14 days prior to registration)

          -  If baseline liver disease, Child Pugh score not exceeding class A (obtained =< 14 days
             prior to registration)

          -  Negative pregnancy test for persons of child-bearing potential (obtained =< 14 days
             prior to registration)

          -  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

          -  FOR MULTIPLE MYELOMA ONLY: Absolute neutrophil count (ANC) >= 1000/uL (obtained =< 14
             days prior to registration)

          -  FOR MULTIPLE MYELOMA ONLY: Platelet (PLT) >= 100,000/uL (obtained =< 14 days prior to
             registration)

          -  FOR MULTIPLE MYELOMA ONLY: Hemoglobin >= 8.5 g/dl (obtained =< 14 days prior to
             registration)

          -  FOR AML ONLY: No ANC restriction (obtained =< 14 days prior to registration)

          -  FOR AML ONLY: PLT >= 10,000/uL (transfusion to get platelets >= 10,000 is allowed)
             (obtained =< 14 days prior to registration)

          -  FOR AML ONLY: Hemoglobin >= 7.5 g/dl (obtained =< 14 days prior to registration)

          -  FOR AML ONLY: Absence of uncompensated disseminated intravascular coagulation (DIC- as
             diagnosed by standard International Society on Thrombosis and Hemostasis [ISTH]
             criteria)

          -  FOR TCL ONLY: ANC >= 1,000/uL (obtained =< 14 days prior to registration)

          -  FOR TCL ONLY: PLT >= 100,000/uL (obtained =< 14 days prior to registration)

          -  FOR TCL ONLY: Hemoglobin >= 8.5 g/dl (obtained =< 14 days prior to registration)

          -  FOR TCL ONLY: Measurable disease by CT or magnetic resonance imaging (MRI): must have
             at least one lesion that has a single diameter of > 2 cm or tumor cells in the blood >
             5 x 10^9/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 central nervous system (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

          -  Eastern Cooperative Oncology Group (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 supraventricular tachycardia [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)

          -  Human immunodeficiency virus (HIV) positive test result or other immunodeficiency or
             immunosuppression

          -  Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy
             considered investigational (used for a non-Food and Drug Administration [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)

          -  ADDITION 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: Multiple : >= 15% plasmas cells or plasmacytoma > 5 cm in
             largest diameter

          -  TCL ONLY: Any mass >= 5 cm

          -  ADDITIONAL EXCLUSION CRITERIA FOR GROUP C (COMBINATION WITH CYCLOPHOSPHAMIDE) ONLY:

          -  Diagnosis of AML

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Incidence of adverse events of grade 3 or higher
Time Frame:	Up to 2 years
Safety Issue:
Description:	Assessed by the Common Terminology Criteria for Adverse Events version 4.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns (by cohort and overall). Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. The rate of grade 3 or higher non-hematologic adverse events, and the rate of grade 4 or higher adverse event (hematologic and non-hematologic) will be computed each with a 95% exact binomial confidence.

Secondary Outcome Measures

Measure:	Clinical response
Time Frame:	Up to 2 years
Safety Issue:
Description:	The number of responses (complete response [CR], very good partial response, partial response [PR], or minimal response for multiple myeloma; CR, CR with incomplete recovery, cytogenetic complete response, PR for acute myeloid leukemia [AML]; CR or PR for T-cell lymphoma [TCL]) will be summarized by simple descriptive summary statistics.

Measure:	Progression-free survival
Time Frame:	From registration to disease progression or death due to any cause, assessed up to 2 years
Safety Issue:
Description:	The distribution of survival time will be estimated using the method of Kaplan-Meier (overall, by dose level, and by disease type).

Measure:	Overall survival
Time Frame:	From registration to death due to any cause, assessed up to 2 years
Safety Issue:
Description:	The distribution of survival time will be estimated using the method of Kaplan-Meier (overall, by dose level, and by disease type).

Details

Phase:	Phase 1
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	Mayo Clinic

Last Updated

August 27, 2021

Clinical Trials /

VSV-hIFNbeta-NIS With or Without Ruxolitinib Phosphate in Treating Patients With Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia, or T-cell Lymphoma