A Phase I Trial to Evaluate Safety and Immunogenicity of a Cytomegalovirus Peptide Vaccine Co-Injected With PF-03512676 Adjuvant in Recipients of Allogeneic Hematopoietic Stem Cell Transplant
A Phase I Trial to Evaluate Safety and Immunogenicity of a Cytomegalovirus Peptide Vaccine Co-Injected With PF-03512676 Adjuvant in Recipients of Allogeneic Hematopoietic Stem Cell Transplant
This randomized phase I trial studies the side effects of vaccine therapy in preventing cytomegalovirus (CMV) infection in patients with hematological malignancies undergoing donor stem cell transplant. Vaccines made from a tetanus-CMV peptide or antigen may help the body build an effective immune response and prevent or delay the recurrence of CMV infection in patients undergoing donor stem cell transplant for hematological malignancies.
PRIMARY OBJECTIVES: I. To discover whether two administrations of 2.5 mg tetanus (Tet)-CMV peptide co-injected with 1 mg of PF-03512676 (tetanus-CMV fusion peptide vaccine), by subcutaneous (SC) route on days 28 and 56 post-hematopoietic cell transplantation (HCT) are safe and well tolerated in human leukocyte antigen (HLA) A*0201 CMV-positive recipients of allogeneic HCT.
SECONDARY OBJECTIVES:
I. To measure levels of CMV-specific T cells in vaccinated compared to unvaccinated HCT recipients (control arm).
II. To assess whether vaccination of HCT recipients with Tet-CMV co-injected with PF03512676 reduces expression of programmed death 1 (PD-1) on CMV-specific T cells.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive Tet-CMV + PF03512675 SC on days 28 and 56 post-HCT.
ARM II: Patients undergo immune monitoring only.
After completion of study treatment, patients are followed up at days 70, 84, 100, 130, 160, and 180.
Inclusion Criteria:
HLA A*0201 subtype
CMV seropositive
Able and willing to sign the informed consent form (ICF)
Willingness to be followed for the planned duration of the trial (6 months post-HCT)
Seronegative for human immunodeficiency virus (HIV), hepatitis C virus (HCV) and active hepatitis B virus (HBV) (surface antigen negative)
Planned related or unrelated HCT, with 8/8 or 7/8 (A, B, C, DRB1) high resolution HLA donor allele matching
HCT for the treatment of hematologic cancers including, but not limited to:
Planned HCT with minimal to no-T cell depletion of graft
Use of contraception up to 90 days post-HCT
Negative pregnancy test for female recipient
DISEASE STATUS: Recipients to be enrolled are patients eligible for allogeneic HCT, who were diagnosed with hematologic cancers including:
Acute lymphoblastic leukemia (ALL); B-precursor ALL; T cell ALL
Acute myeloid leukemia (AML), acute promyelocytic leukemia; treatment related AML
Chronic lymphoid leukemia; adult T cell leukemia/lymphoma, chronic lymphocytic leukemia not otherwise specified (NOS), hairy cell leukemia; prolymphocytic leukemia (B or T); T cell large granular (gran.) lymphocytic (lymph.) leukemia (leuk)
Chronic myeloproliferative disease (CML); chronic eosinophilic leukemia (CEL)/hypereosinophilic syndrome; chronic idiopathic myelofibrosis; CML - Philadelphia chromosome; essential thrombocythemia; polycythemia vera
Leukemia, not otherwise specified (NOS)
Myelodysplastic syndrome, NOS; chronic myelomonocytic leukemia
Hodgkin lymphoma, NOS; Hodgkin lymphoma nodular lymphocyte predominant (LP), NOS; Hodgkin lymphoma - like post-transplant lymphoproliferative disorder (PTLD)
Lymphoma, NOS
Non-Hodgkin lymphoma (NHL); anaplastic large-cell lymphoma (ALCL), cutaneous, ALCL, systemic; Burkitt lymphoma/leukemia; cutaneous T-cell lymphoma (CTCL)/mycosis fungoides; CTCL/Sezary syndrome; diffuse large B-cell lymphoma; mucosa associated lymphoid tissue (MALT)-lymphoma; extranodal natural killer (NK)/T cell lymphoma, extranodal NK/T lymphoma nasal; follicular lymphoma; lymphoplasmacytic lymphoma mantle cell lymphoma; mediastinal large B-cell lymphoma; nodal marginal zone B-cell lymphoma (lymph.); NHL aggressive, NOS; NHL indolent, NOS; NHL, NOS; peripheral T cell lymphoma, NOS; PTLD (monoclonal); PTLD (polyclonal); precursor (precur.) B-lymphoblastic lymphoma; precur T-lymphoblastic lymphoma; primary central nervous system (CNS) lymphoma; primary effusion lymphoma; small lymphocytic lymphoma, NOS
Myeloma, NOS; monoclonal gammopathy of undetermined significance (MGUS); solitary plasmacytoma
Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
All medications, supportive care, blood products or radiation therapy taken or administered during the trial will be documented in the subject's clinical/hospital and case report form (CRF), using City of Hope (COH) guidelines; the subject's clinical information will be recorded on the appropriate CRF
Concurrent enrollment in other clinical trials using an investigational product is prohibited
The use of alemtuzumab for immunosuppression is not permitted in this study
Prophylactic therapy with CMV immunoglobulin or prophylactic antiviral CMV treatment is not allowed
Medications that might interfere with the evaluation of the investigational product should not be administered, from 30 days prior to participation on the trial and up to 14 days after the second vaccination (day 70 post-HCT); medications in this category include, but are not limited to:
Antiviral treatment for herpes simplex virus (HSV), human herpes virus 6 (HHV6), Epstein-Barr virus (EBV) and adenovirus including the use of GVC/VAL, FOS, Cidofovir, CMX-001 may also suppress reactivation of CMV, thus it will not be allowed in this study; patients requiring such treatment before randomization (day 28) will be removed from the study and replaced; reasons for removal will be reported in the patient's CRF
All enrolled recipients who will require anti-CMV therapy before day 28 will be replaced, treated and monitored as required by COH standard of care; GVC/VAL, FOS, Cidofovir, CMX-001 may be used according to COH standard of care (SOC) for preemptive management of CMV viremia; should antiviral treatment be required after day 28, the planned 2nd vaccine injection at day 56 will not be administered (vaccine arm only)
All subjects must have the ability to understand and the willingness to sign a written informed consent
Exclusion Criteria:
A poor-risk patient, as defined by any of the following:
Planned immunosuppression with alemtuzumab or any equivalent in vivo T-cell depleting agent
In vitro T cell depleted graft
Planned prophylactic therapy with CMV immunoglobulin
Planned CMV prophylactic therapy
Experimental anti-CMV chemotherapy in the last 6 months
Diagnosed with autoimmune disease
Receipt of the following substances:
Pregnant and/or breast feeding if a female recipient
Refusing to use contraception up to 90 days post-HCT
POST-HCT STUDY-SPECIFIC EXCLUSIONS:
On days 28 and 56 post-HCT (immunization day for the vaccine arm) all study recipients (vaccine and observation arms) will be reviewed for eligibility and ruled ineligible to initiate or continue in the study and receive vaccination (for the vaccine arm) if: