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A Vaccine (VSV-hIFNβ-NIS) with or Without Cyclophosphamide and Combinations of Ipilimumab, Nivolumab, and Cemiplimab in Treating Relapsed or Refractory Multiple Myeloma, Acute Myeloid Leukemia or Lymphoma

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Conditions

B-Cell Non-Hodgkin LymphomaHistiocytic and Dendritic Cell NeoplasmMyelodysplastic SyndromePreviously Treated Myelodysplastic SyndromeRecurrent Adult Acute Myeloid LeukemiaRecurrent Anaplastic Large Cell LymphomaRecurrent Angioimmunoblastic T-Cell LymphomaRecurrent Mycosis FungoidesRecurrent Plasma Cell MyelomaRecurrent Primary Cutaneous T-Cell Non-Hodgkin LymphomaRecurrent T-Cell Non-Hodgkin LymphomaRefractory Acute Myeloid LeukemiaRefractory Anaplastic Large Cell LymphomaRefractory Angioimmunoblastic T-Cell LymphomaRefractory Mycosis FungoidesRefractory Peripheral T-Cell Lymphoma, Not Otherwise SpecifiedRefractory Plasma Cell MyelomaRefractory Primary Cutaneous T-Cell Non-Hodgkin LymphomaRefractory T-Cell Non-Hodgkin Lymphoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This phase I trial studies the best dose and side effects of the VSV-hIFNβ-NIS vaccine with or without cyclophosphamide and combinations of ipilimumab, nivolumab, and cemiplimab in treating patients with multiple myeloma, acute myeloid leukemia or lymphoma that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). VSV-IFNβ-NIS is a modified version of the vesicular stomatitis virus (also called VSV). This virus can cause infection and when it does it typically infects pigs, cattle, or horses but not humans. The VSV used in this study has been altered by having two extra genes (pieces of DNA) added. The first gene makes a protein called NIS that is inserted into the VSV. NIS is normally found in the thyroid gland (a small gland in the neck) and helps the body concentrate iodine. Having this additional gene will make it possible to track where the virus goes in the body (which organs). The second addition is a gene for human interferon beta (β) or hIFNβ. Interferon is a natural anti-viral protein, intended to protect normal healthy cells from becoming infected with the virus. VSV is very sensitive to the effect of interferon. Many tumor cells have lost the capacity to either produce or respond to interferon. Thus, interferon production by tumor cells infected with VSV-IFNβ-NIS will protect normal cells but not the tumor cells. The VSV with these two extra pieces is referred to as VSV-IFNβ-NIS. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill cancer cells. It may also lower the body's immune response. Immunotherapy with monoclonal antibodies, such as ipilimumab, nivolumab, and cemiplimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving VSV-IFNβ-NIS with or without cyclophosphamide and combinations of ipilimumab, nivolumab, and cemiplimab may be safe and effective in treating patients with recurrent peripheral 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, Lymphomas, or Histiocytic/Dendritic Cell Neoplasms

Quick Facts

Study Start:2017-04-04
Study Completion:2032-04-01
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT03017820

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Age \>= 18 years
  2. * Relapsed or refractory disease as follows:
  3. * Groups A, B, C or D: Multiple myeloma (MM) previously treated with an immunomodulatory imide drug (IMID), a proteosome inhibitor, and an alkylating agent
  4. * All Groups except D: 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
  5. * Group B and C only: B-cell lymphoma (other than Burkitt's lymphoma), or histiocytic/dendritic cell neoplasms (HCN) at any stage
  6. * 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)
  7. * Group F only: Expansion Cohort for B-cell lymphoma (other than Burkitt's lymphoma) with low tumor burden
  8. * Group G only: Expansion Cohort for peripheral T cell lymphoma (PTCL) with low tumor burden
  9. * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2 times upper limit of normal (ULN) (obtained =\< 15 days prior to registration)
  10. * Creatinine =\< 2.0 mg/dL (obtained =\< 15 days prior to registration)
  11. * Direct bilirubin =\< 1.5 x ULN (obtained =\< 15 days prior to registration)
  12. * International normalized ratio (INR)/prothrombin time (PT) and activated partial thromboplastin time (aPTT) =\< 1.5 x ULN (obtained =\< 15 days prior to registration)
  13. * If baseline liver disease, Child Pugh score not exceeding class A (obtained =\< 15 days prior to registration)
  14. * Negative pregnancy test for persons of child-bearing potential (obtained =\< 15 days prior to registration)
  15. * FOR MULTIPLE MYELOMA ONLY: Measurable disease of multiple myeloma as defined by at least ONE of the following:
  16. * Serum monoclonal protein \>= 1.0 g/dL by protein electrophoresis
  17. * \>= 200 mg of monoclonal protein in the urine on 24-hour electrophoresis
  18. * Serum immunoglobulin free light chain \>= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
  19. * FOR MULTIPLE MYELOMA ONLY: Absolute neutrophil count (ANC) \>= 1000/uL (obtained =\< 14 days prior to registration)
  20. * FOR MULTIPLE MYELOMA ONLY: Platelet (PLT) \>= 100,000/uL (obtained =\< 14 days prior to registration)
  21. * FOR MULTIPLE MYELOMA ONLY: Hemoglobin \>= 8.5 g/dl (obtained =\< 14 days prior to registration)
  22. * FOR AML ONLY: No ANC restriction (obtained =\< 14 days prior to registration)
  23. * FOR AML ONLY: PLT \>= 10,000/uL (transfusion to get platelets \>= 10,000 is allowed) (obtained =\< 14 days prior to registration)
  24. * FOR AML ONLY: Hemoglobin \>= 7.5 g/dl (obtained =\< 14 days prior to registration)
  25. * FOR AML ONLY: Absence of uncompensated disseminated intravascular coagulation (DIC- as diagnosed by standard International Society on Thrombosis and Hemostasis \[ISTH\] criteria)
  26. * FOR TCL/BCL ONLY: ANC \>= 1,000/uL (obtained =\< 14 days prior to registration)
  27. * FOR TCL/BCL ONLY: PLT \>= 100,000/uL (obtained =\< 14 days prior to registration)
  28. * FOR TCL/BCL ONLY: Hemoglobin \>= 8.5 g/dl (obtained =\< 14 days prior to registration)
  29. * 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
  30. * FOR HCN ONLY: ANC \>= 1,000/uL obtained =\< 15 days prior to registration
  31. * FOR HCN ONLY: PLT \>= 100,000/uL obtained =\< 15 days prior to registration
  32. * FOR HCN ONLY: Hemoglobin \>= 8.0 g/dl obtained =\< 15 days prior to registration
  33. * 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
  34. * Absence of active central nervous system (CNS) involvement; NOTE: pre-enrollment lumbar puncture not mandatory
  35. * Ability to provide written informed consent
  36. * Willingness to return to Mayo Clinic for follow-up
  37. * Life expectancy \>= 12 weeks
  38. * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
  39. * Willing to provide mandatory biological specimens for research purposes
  1. * Availability of and patient acceptance of curative therapy
  2. * Uncontrolled infection
  3. * Active tuberculosis or hepatitis, or chronic hepatitis
  4. * Any of the following prior therapies:
  5. * Chemotherapy (IMIDs, alkylating agents, proteosome inhibitors) =\< 2 weeks prior to registration
  6. * Immunotherapy (monoclonal antibodies) =\< 4 weeks prior to registration
  7. * Experimental agent in case of AML or TCL within 4 half-lives of the last dose of the agent
  8. * 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 \[SVT\])
  9. * 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)
  10. * Human immunodeficiency virus (HIV) positive test result or other immunodeficiency or immunosuppression
  11. * 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);
  12. * NOTE: in AML, the concurrent use of hydroxyurea to help control proliferative counts is allowed throughout the treatment protocol;
  13. * 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)
  14. * 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:
  15. * Pregnant women or women of reproductive ability who are unwilling to use effective contraception
  16. * Nursing women
  17. * 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
  18. * AML ONLY: Current disseminated intravascular coagulopathy (DIC)
  19. * ADDITIONAL EXCLUSION CRITERIA FOR GROUP A (LOW TUMOR BURDEN) ONLY:
  20. * Diagnosis of AML
  21. * Multiple myeloma only: \> 25% plasma cells or plasmacytoma \> 5cm in largest diameter
  22. * Lymphoma or HCN only: Any mass \>5cm
  23. * Diagnosis of Burkitt's lymphoma
  24. * ADDITIONAL EXCLUSION CRITERIA FOR GROUP B (HIGH TUMOR BURDEN) ONLY:
  25. * Diagnosis of AML
  26. * Diagnosis of Burkitt's lymphoma
  27. * ADDITIONAL EXCLUSION CRITERIA FOR GROUP C (COMBINATION WITH CYCLOPHOSPHAMIDE) ONLY:
  28. * Diagnosis of AML
  29. * Diagnosis of Burkitt's lymphoma
  30. * ADDITIONAL EXCLUSION CRITERIA FOR GROUP D AND E (COMBINATION WITH IPILIMUMAB AND NIVOLUMAB OR CEMIPLIMAB) ONLY:
  31. * Diagnosis of AML
  32. * Diagnosis of AITL
  33. * Hypersensitivity to ipilimumab or its excipients
  34. * ADDITIONAL EXCLUSION CRITERIA FOR GROUP F (BCL EXPANSION COHORT) ONLY:
  35. * Diagnosis of Burkitt's lymphoma
  36. * ADDITIONAL EXCLUSION CRITERIA FOR GROUP G (PTCL EXPANSION COHORT) ONLY:
  37. * Diagnosis of cutaneous TCL

Contacts and Locations

Study Contact

Clinical Trials Referral Office
CONTACT
855-776-0015
mayocliniccancerstudies@mayo.edu

Principal Investigator

Nora Bennani, M.D.
PRINCIPAL_INVESTIGATOR
Mayo Clinic in Rochester
Joselle Cook, M.B.B.S.
PRINCIPAL_INVESTIGATOR
Mayo Clinic in Rochester

Study Locations (Sites)

Mayo Clinic in Arizona
Scottsdale, Arizona, 85259
United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
United States

Collaborators and Investigators

Sponsor: Mayo Clinic

  • Nora Bennani, M.D., PRINCIPAL_INVESTIGATOR, Mayo Clinic in Rochester
  • Joselle Cook, M.B.B.S., PRINCIPAL_INVESTIGATOR, Mayo Clinic in Rochester

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2017-04-04
Study Completion Date2032-04-01

Study Record Updates

Study Start Date2017-04-04
Study Completion Date2032-04-01

Terms related to this study

Additional Relevant MeSH Terms

  • B-Cell Non-Hodgkin Lymphoma
  • Histiocytic and Dendritic Cell Neoplasm
  • 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