Multi-antigen CMV-Modified Vaccinia Ankara Vaccine in Reducing CMV Related Complications in Patients With Blood Cancer Undergoing Donor Stem Cell Transplant

NCT03438344 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 17366
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief Summary

This randomized phase II trial studies how well multi-antigen cytomegalovirus (CMV)-modified vaccinia Ankara vaccine works in reducing CMV related complications in patients with blood cancer who are undergoing donor stem cell transplant. Vaccines made from a gene-modified virus may help the body build an effective immune response to kill cancer cells.

Conditions

Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia in Remission; Bone Marrow Transplantation Recipient; Chronic Lymphocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Hematopoietic Cell Transplantation Recipient; Hodgkin Lymphoma; Myelodysplastic Syndrome; Myelofibrosis; Myeloproliferative Neoplasm; Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Cytomegalovirus (CMV) events

  Will include any CMV reactivation (detection of \>= 1250 U/mL plasma), low-level reactivation prompting antiviral therapy, or CMV disease (defined by histology) prior to day 100 post-hematopoietic cell transplantation (HCT).

  Up to 3 years

Secondary Outcomes (18)

• Non-relapse mortality (NRM)

  At 100 days post HCT

• Severe (grade 3-4) acute graft versus host disease (GVHD)

  Up to 3 years

• Grade 3-4 adverse events probably/definitely related to the vaccination and modified vaccinia Ankara vector persistence

  Up to 3 years

• Duration of viremia

  Up to 3 years

• Duration of anti-CMV therapy

  Up to 3 years

Study Arms (2)

Arm I (CMV-MVA triplex vaccine)

EXPERIMENTAL

Patients receive multi-antigen CMV-modified vaccinia Ankara vaccine via injection on days 28 and 56 post-HCT.

Biological: Multi-antigen CMV-Modified Vaccinia Ankara Vaccine; Other: Laboratory Biomarker Analysis

Arm II (placebo)

PLACEBO COMPARATOR

Patients receive placebo via injection on days 28 and 56 post-HCT.

Other: Laboratory Biomarker Analysis; Other: Placebo

Interventions

Multi-antigen CMV-Modified Vaccinia Ankara Vaccine BIOLOGICAL

Given IM

Also known as: CMV-MVA Triplex Vaccine

Arm I (CMV-MVA triplex vaccine)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (CMV-MVA triplex vaccine); Arm II (placebo)

Placebo OTHER

Given IM

Also known as: placebo therapy, PLCB, sham therapy

Arm II (placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects must have the ability to understand and the willingness to sign a written informed consent
• Participant must be willing to comply with study and/or follow-up procedures, including willingness to be followed for one year post-HCT
• Planned peripheral blood stem cell (PBSC) or bone marrow (BM) HCT for the treatment of the following hematologic malignancies:
• Lymphoma (Hodgkin and non-Hodgkin)
• Myelodysplastic syndrome
• Acute lymphoblastic leukemia in first or second remission (for acute lymphoblastic leukemia/lymphoblastic lymphoma, the disease status must be in hematologic remission by bone marrow and peripheral blood; persistent lymphadenopathy on computed tomography \[CT\] or CT/positron emission tomography \[PET\] scan without progression is allowed)
• Acute myeloid leukemia in first or second remission
• Chronic myelogenous leukemia in first chronic or accelerated phase, or in second chronic phase
• Other hematologic malignancies judged appropriate by the clinical principal investigators (PIs), including chronic lymphocytic leukemia, myeloproliferative disorders and myelofibrosis; patients with multiple myeloma and those with non-malignant disease such as aplastic anemia are excluded
• Adult cases of multiple myeloma (MM) are excluded; adults with aplastic anemia are excluded; patients undergoing a second haploHCT are not eligible (patients who have undergone a previous autologous HCT are eligible)
• Patients receiving myeloablation (MA) or reduced intensity conditioning (RIC) are allowed
• CMV seropositive (recipient)
• Planned related HCT with molecular 3/6 (haploidentical) intermediate/high resolution human leukocyte antigen (HLA) donor allele matching
• Planned HCT with minimal to no-T cell depletion of graft
• Conditioning and immunosuppressive regimens according to institutional guidelines are permitted

You may not qualify if:

• Any prior investigational CMV vaccine
• Experimental anti-CMV chemotherapy in the last 6 months
• Live attenuated vaccines
• Medically indicated subunit (Engerix-B for HBV, Gardasil for HPV) or killed vaccine (e.g. influenza, pneumococcal, or allergy treatment with antigen injections)
• Allergy treatment with antigen injections
• Alemtuzumab or any equivalent in vivo T-cell depleting agent (or CD34+ selection)
• Antiviral medications with known therapeutic effects on CMV such as ganciclovir/valganciclovir (GCV/VAL), foscarnet (FOS), Cidofovir, CMX-001, maribavir; acyclovir has no known therapeutic efficacy against CMV and is allowable as standard of care to prevent herpes simplex virus (HSV)
• Prophylactic therapy with CMV immunoglobulin or prophylactic antiviral CMV treatment
• Conditioning regimens 30 days (d) prior to trial participation and up to d28 post-HCT
• Disease-based radiation therapy (not total body irradiation)
• Other investigational product-concurrent enrollment in other clinical trials using any investigational new drug (IND) drugs with unknown effects on CMV or with unknown toxicity profiles is prohibited
• Other medications that might interfere with the evaluation of the investigational product
• Patients with active autoimmune conditions requiting systemic immunosuppressive therapy within the previous 5 years at not eligible
• Patients considered by PIs/protocol team to have a complicated prior therapy or HCT regimen, or who have a low survival probability (e.g., refractory leukemia and/or undergoing 2nd HCT)
• Poor risk disease/disease status including: chronic myeloid leukemia (CML) in blast crisis, acute myeloid leukemia (AML)/acute lymphoblastic leukemia (ALL) beyond 2nd remission, multiple myeloma, and aplastic anemia

Sponsors & Collaborators

• City of Hope Medical Center: lead

Study Sites (3)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Accelerated Phase; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid, Chronic-Phase; Hodgkin Disease; Myelodysplastic Syndromes; Primary Myelofibrosis; Myeloproliferative Disorders; Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, B-Cell; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma

Study Officials

• Ryotaro Nakamura, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2017
• First Posted: February 19, 2018
• Study Start: December 1, 2018
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: November 21, 2018

Record last verified: 2018-11

Locations

US (3)