Vaccine Therapy in Reducing the Frequency of Cytomegalovirus Events in Patients With Hematologic Malignancies Undergoing Donor Stem Cell Transplant

NCT02396134 | Completed Phase 2 Results DMC

• 3 other identifiers: 13494NCI-2015-00283R01CA181045
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 5

Brief Summary

This randomized phase II trial studies how well vaccine therapy works in reducing the frequency of cytomegalovirus severe infections (events) in patients with hematologic malignancies undergoing donor stem cell transplant. Vaccines made from a peptide may help the body build an effective immune response and may reduce cytomegalovirus events after donor stem cell transplant.

Conditions

Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Hodgkin Lymphoma; Adult Non-Hodgkin Lymphoma; Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Cytomegaloviral Infection; Hematopoietic and Lymphoid Cell Neoplasm; HLA-A*0201 Positive Cells Present; Myelodysplastic Syndrome; Adult Lymphoblastic Lymphoma; Chronic Lymphocytic Leukemia; Myelofibrosis; Myeloproliferative Neoplasm

Outcome Measures

Primary Outcomes (1)

• Cumulative Incidence of CMV at 100 Days

  The primary endpoint was CMV event. A CMV event encompasses detection of CMV by either qPCR (termed "reactivation": DNAemia at ≥500 gc/ml = 1250iu/ml) or by tissue histology (end-organ disease). The cumulative incidence was calculated as competing risks using the method of Gooley with death viewed as a competing risk.

  Up to day 100 after HCT

Secondary Outcomes (2)

• Non-Relapse Mortality (NRM) at 100 Days

  Up to 100 days after transplant

• Cumulative Incidence of Relapse at One Year

  Up to 365 days after HCT

Study Arms (2)

Arm I (CMVpp65-A*0201 peptide vaccine)

EXPERIMENTAL

Patients receive CMVpp65-A\*0201 peptide vaccine SC on days 28 and 56 after HCT.

Biological: CMVpp65-A*0201 peptide vaccine; Other: Laboratory Biomarker Analysis

Arm II (placebo)

PLACEBO COMPARATOR

Patients receive placebo SC on days 28 and 56 after HCT.

Other: Placebo; Other: Laboratory Biomarker Analysis

Interventions

CMVpp65-A*0201 peptide vaccine BIOLOGICAL

Given SC

Arm I (CMVpp65-A*0201 peptide vaccine)

Placebo OTHER

Given SC

Also known as: placebo, Placebo, placebo therapy, PLCB, sham therapy

Arm II (placebo)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (CMVpp65-A*0201 peptide vaccine); Arm II (placebo)

Eligibility Criteria

• Age: 18 Years - 75 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 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 needs to 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 including chronic lymphocytic leukemia, myeloproliferative disorders and myelofibrosis; patients with multiple myeloma and those with non-malignant disease such as aplastic anemia are excluded
• HLA A\*0201 High resolution, 4-digit typing is required at HLA-A2 to ensure A\*0201 status.
• CMV seropositive (recipient)
• Planned related or unrelated HCT, with HLA donor allele matching; related donor must be an 8/8 match for HLA-A, -B, and -C at intermediate (or higher) resolution, and -DRB1 at high resolution using deoxyribonucleic acid (DNA)-based typing; unrelated donor must be an 8/8 match at HLA-A, -B, -C, and -DRB1 at high resolution using DNA-based typing; patients undergoing a second allo HCT are not eligible (patients who have undergone a previous autologous HCT are eligible)
• Planned HCT with no ex-vivo T cell depletion of graft; conditioning and immunosuppressive regimens according to institutional guidelines are permitted
• Negative serum or urine beta-human chorionic gonadotropin (HCG) test (female patient of childbearing potential only) within two weeks of registration
• Seronegative for human immunodeficiency virus (HIV), hepatitis C virus (HCV) and active hepatitis B virus (HBV) (surface antigen negative) within 2 months of registration

You may not qualify if:

• Any prior investigational CMV vaccine
• Experimental anti-CMV chemotherapy in the last 6 months
• Planned medications from the time of HCT to day 70 post-HCT:
• Live attenuated vaccines
• Medically indicated subunit (Engerix-B for HBV; Gardasil for human papilloma virus \[HPV\]) or killed vaccines (e.g. influenza, pneumococcal, or allergy treatment with antigen injections)
• Allergy treatment with antigens injections
• Alemtuzumab or any equivalent in vivo T-cell depleting agent; this includes anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide
• Antiviral medications with known therapeutic effects against CMV such as ganciclovir (GCV)/valine (VAL), foscarnet (FOS), cidofovir, hexadecyloxypropyl-cidofovir (CMX-001) and maribavir; acyclovir has no therapeutic efficacy against CMV and is allowable as standard of care to prevent herpes simplex virus (HSV)
• Other investigational product - concurrent enrollment in other clinical trials using an investigational product is prohibited
• Other medications that might interfere with the evaluation of the investigational product
• Patients with active autoimmune conditions requiring systemic immunosuppressive therapy within the previous 5 years are not eligible
• Pregnant women and women who are lactating; breastfeeding should be discontinued if the mother is enrolled on this study
• Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., social/psychological issues, etc
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Gooley TA, Leisenring W, Crowley J, Storer BE. Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med. 1999 Mar 30;18(6):695-706. doi: 10.1002/(sici)1097-0258(19990330)18:63.0.co;2-o.

  PMID: 10204198 RESULT

MeSH Terms

Conditions

Leukemia, Myeloid, Accelerated Phase; Hodgkin Disease; Lymphoma, Non-Hodgkin; Leukemia, Myeloid, Chronic-Phase; Cytomegalovirus Infections; Hematologic Neoplasms; Myelodysplastic Syndromes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Primary Myelofibrosis; Myeloproliferative Disorders

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; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Neoplasms by Site; Leukemia, Lymphoid; Leukemia, B-Cell

Results Point of Contact

• Title: Dr. Ryotaro Nakamura
• Organization: City of Hope

rnakamura@coh.org

626-359-8111

Study Officials

• Ryotaro Nakamura, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: March 12, 2015
• First Posted: March 24, 2015
• Study Start: May 21, 2015
• Primary Completion: March 4, 2018
• Study Completion: September 19, 2024
• Last Updated: March 3, 2025
• Results First Posted: July 12, 2023

Record last verified: 2025-02

Locations

US (5)