Non Hodgkin Lymphoma Clinical Trial

VSV-hIFNbeta-NIS in Treating Patients With Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia or Lymphoma

Summary

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.

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Full Description

PRIMARY OBJECTIVE:

I. To determine the maximum tolerated dose (MTD) of VSV-hIFNβ-NIS in different treatment regimens (alone [Group A, F, G] in combination with ruxolitinib [Group B] and in combination with cyclophosphamide [Group C]) in patients with relapsed/refractory multiple myeloma, acute myeloid leukemia, T and B-cell lymphoma, or histiocytic/dendritic cell neoplasms; in combination with ipilimumab and nivolumab in patients with multiple myeloma [Group D] and in combination with ipilimumab and cemiplimab in patients with T-cell lymphoma [Group E].

SECONDARY OBJECTIVES:

I. To determine the safety profile of VSV-hIFNbeta-NIS (alone and in combination).

II. To estimate clinical response rate of VSV-hIFNbeta-NIS (alone and in combination) in patients with relapsed/refractory multiple myeloma, acute myeloid leukemia, T-cell and B-cell lymphoma or histiocytic/dendritic cell neoplasms overall and by disease type.

III. To estimate progression-free and overall survival of VSV-hIFNbeta-NIS (alone and in combination) in patients with relapsed/refractory multiple myeloma, acute myeloid leukemia, T and B-cell lymphoma, or histiocytic/dendritic cell neoplasms 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 in the absence of disease progression or unacceptable toxicity.

GROUP B: **NO LONGER ENROLLING** Patients receive VSV-IFNbeta-NIS IV over 30 minutes on day 1 and cyclophosphamide IV over 2 hours on day 2 in the absence of disease progression or unacceptable toxicity.

GROUP C: **NO LONGER ENROLLING** Patients receive VSV-IFNbeta-NIS IV over 30 minutes on day 1, ipilimumab IV over 30 minutes on day -3 and nivolumab IV over 30 minutes on day -3 in the absence of disease progression or unacceptable toxicity.

GROUP D: Patients receive VSV-IFNbeta-NIS IV over 30 minutes on day 1, ipilimumab IV over 30 minutes on day -3 and cemiplimab IV over 30 minutes on day -3 in the absence of disease progression or unacceptable toxicity.

Patients undergo computed tomography (CT) scan, position emission tomography (PET) scan throughout the study. Patients may undergo tumor biopsy, bone marrow biopsy and blood sample collection throughout the study.

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.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Age >= 18 years

Relapsed or refractory:

Groups A, B, C or D: Multiple myeloma (MM) previously treated with an immunomodulatory imide drug (IMID), a proteosome inhibitor, and an alkylating agent
Groups A, B, C only: Relapsed peripheral T-cell lymphoma (PTCL) of the following histologies: peripheral T-cell lymphoma-NOS (PTCL-NOS); 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
Group G only: Expansion Cohort for peripheral T cell lymphoma (PTCL) with low tumor burden
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2 times upper limit of normal (ULN) (obtained =< 15 days prior to registration)
Creatinine =< 2.0 mg/dL (obtained =< 15 days prior to registration)
Direct bilirubin =< 1.5 x ULN (obtained =< 15 days prior to registration)
International normalized ratio (INR)/prothrombin time (PT) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN (obtained =< 15 days prior to registration)
If baseline liver disease, Child Pugh score not exceeding class A (obtained =< 15 days prior to registration)
Negative pregnancy test for persons of child-bearing potential (obtained =< 15 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/BCL ONLY: ANC >= 1,000/uL (obtained =< 14 days prior to registration)
FOR TCL/BCL ONLY: PLT >= 100,000/uL (obtained =< 14 days prior to registration)
FOR TCL/BCL ONLY: Hemoglobin >= 8.5 g/dl (obtained =< 14 days prior to registration)
FOR TCL/BCL 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
FOR HCN ONLY: ANC >= 1,000/uL obtained =< 15 days prior to registration
FOR HCN ONLY: PLT >= 100,000/uL obtained =< 15 days prior to registration
FOR HCN ONLY: Hemoglobin >= 8.0 g/dl obtained =< 15 days prior to registration
FOR HCN ONLY: 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 x10^9/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 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 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
AML ONLY: Current disseminated intravascular coagulopathy (DIC)

ADDITIONAL EXCLUSION CRITERIA FOR GROUP A (LOW TUMOR BURDEN) ONLY:

Diagnosis of AML
Multiple myeloma only: > 25% plasma cells or plasmacytoma > 5cm in largest diameter
Lymphoma or HCN only: Any mass >5cm
Diagnosis of Burkitt's lymphoma

ADDITIONAL EXCLUSION CRITERIA FOR GROUP B (HIGH TUMOR BURDEN) ONLY:

Diagnosis of AML
Diagnosis of Burkitt's lymphoma

ADDITIONAL EXCLUSION CRITERIA FOR GROUP C (COMBINATION WITH CYCLOPHOSPHAMIDE) ONLY:

Diagnosis of AML
Diagnosis of Burkitt's lymphoma

ADDITIONAL EXCLUSION CRITERIA FOR GROUP D AND E (COMBINATION WITH IPILIMUMAB AND NIVOLUMAB OR CEMIPLIMAB) ONLY:

Diagnosis of AML
Diagnosis of AITL
Hypersensitivity to ipilimumab or its excipients

ADDITIONAL EXCLUSION CRITERIA 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

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 1

Estimated Enrollment:

120

Study ID:

NCT03017820

Recruitment Status:

Recruiting

Sponsor:

Mayo Clinic

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There are 2 Locations for this study

See Locations Near You

Mayo Clinic in Arizona
Scottsdale Arizona, 85259, United States More Info
Clinical Trials Referral Office
Contact
855-776-0015
[email protected]
Javier L. Munoz, M.D.
Principal Investigator
Mayo Clinic in Rochester
Rochester Minnesota, 55905, United States More Info
Clinical Trials Referral Office
Contact
855-776-0015
[email protected]
Nora Bennani, M.D.
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 1

Estimated Enrollment:

120

Study ID:

NCT03017820

Recruitment Status:

Recruiting

Sponsor:


Mayo Clinic

How clear is this clinincal trial information?

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