Non Hodgkin Lymphoma Clinical Trial

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

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:

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, or T and B-cell lymphoma, or histiocytic/dendritic cell neoplasms; and in combination with ruxolitinib and cyclophosphamide [Group C] in relapsed/refractory multiple myeloma patients; in combination with ipilimumab and nivolumab in patients with multiple myeloma [Group D] and in patients with T-cell lymphoma [Group E].

SECONDARY OBJECTIVES:

I. To determine the safety profile of VSV-hIFNβ-NIS (alone and in combination with ruxolitinib). II. To estimate clinical response rate of VSV-hIFNβ-NIS (alone and in combination with ruxolitinib) in patients with relapsed/refractory multiple myeloma, acute myeloid leukemia, or T and B-cell lymphoma, or histiocytic/dendritic cell neoplasms overall and by disease type. III. To estimate progression-free and overall survival of VSV-hIFNβ-NIS (alone and in combination with ruxolitinib) in patients with relapsed/refractory multiple myeloma, acute myeloid leukemia, or 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-hIFNβ-NIS using planar and SPECT/CT or TFB-PET imaging. II. To assess virus replication, viremia, viral shedding in urine and respiratory secretions, and virus persistence after systemic administration of VSV-hIFNβ- NIS. III. To characterize the pharmacodynamics (PD) of VSV-IFNβ-NIS by way of measuring serum interferon-β and also VSV-RT-PCR of VSV-IFNβ-NIS. IV. Assess CD8+ T cell (both general and VSV-IFNβ-NIS specific) and 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 IV VSV-IFNβ-NIS. VII. To identify the best dose of VSV-hIFNβ-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 study consists of a single dose escalation scheme to determine the maximum tolerated dose (MTD) of VSV-hIFNβ-NIS when given to patients with relapsed or refractory multiple myeloma, acute myeloid leukemia, or lymphomas (TCL or BCL), or histiocytic dendritic cell neoplasms. Patients are assigned to 1 of 7 groups.

Group A (low tumor burden): VSV-hIFNβ-NIS alone IV over 30 minutes Day 1. Patients undergo SPECT/CT scans at baseline, and at days 3 and 8 after VSV-IFNbeta-NIS infusion.

Group B (high tumor burden): VSV-hIFNβ-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.

Group C: VSV-hIFNβ-NIS with cyclophosphamide Patients receive VSV-IFNbeta-NIS IV over 30 minutes on day 1 and 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.

Groups D and E: VSV-hIFNβ-NIS with ipilimumab and nivolumab. VSV-hIFNβ-NIS IV over 30 minutes on day 1 and Nivolumab and Ipilimumab IV over 30 minutes on day -3. NOTE: Nivolumab is given first followed by ipilimumab Patients undergo SPECT/CT scans at baseline, and at days 3 and 8 after VSV-IFNbeta-NIS infusion.

Groups F: (BCL) and G (PTCL) VSV alone. VSV-hIFNβ-NIS alone IV over 30 minutes Day 1. 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.

View Eligibility Criteria

Eligibility Criteria

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

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 3 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 Florida
Jacksonville Florida, 32224, United States
Mayo Clinic in Rochester
Rochester Minnesota, 55905, United States More Info
Clinical Trials Referral Office
Contact
855-776-0015
[email protected]
Martha Q. Lacy, 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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