Clinical trial NCT01827137: WT1 Vaccine Treatment of Patients With Multiple Myeloma After Autologous Stem Cell Transplantation
Official title: A Pilot Trial of a WT1 Analog Peptide Vaccine in Patients With Multiple Myeloma Following Autologous Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: WT1 Analog Peptide Vaccine
12-288
Galinpepimut-S
GPS
Maintenance therapy
Autologous Stem Cell Transplant (ASCT)
Wilms Tumor 1
Immunotherapeutic Agent
Post-ASCT maintenance
SLS-001
Lead sponsor: Sellas Life Sciences Group
Sponsor class: INDUSTRY
Collaborators: name: Memorial Sloan Kettering Cancer Center
First posted: 2013-04-09
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is to assess the immune response after vaccination with a peptide vaccine called galinpepimut-S (or GPS) in a type of blood cancer called multiple myeloma. A protein called WT1 is often present in cancerous cells and GPS can train the immune system to recognize and kill the cancerous cells containing WT1. This study will also assess the safety of GPS, effect on disease, and on survival.

Participants who has undergone autologous stem cell transplant (ASCT) will receive vaccinations with GPS every 2 weeks for 10 weeks (a total of 6 vaccinations). Vaccinations will start 12 to 22 days after ASCT. In the absence of disease progression and if clinically stable after the first 6 vaccinations, participants may continue to receive six more vaccinations every month. The use of post-ASCT maintenance therapy is allowed starting from 3 months after transplant.

Detailed description: This is an early phase clinical study conducted in patients with newly diagnosed high-risk multiple myeloma to examine the effects of vaccination with galinpepimut-S (GPS) on clinical and immunobiological indices. The study is titled "A Pilot Trial of a WT1 Analog Peptide Vaccine (Galinpepimut-S) in Patients With Multiple Myeloma Following Autologous Stem Cell Transplantation" and is designed as a single-arm, single-institution, open-label study. The primary objective is to assess immune response 12 to 14 weeks after administration of GPS in patients with new diagnosed multiple myeloma (MM) following autologous stem cell transplant (ASCT). Secondary objective includes assessing the safety profile, progression-free survival, and overall survival.

Galinpepimut-S (GPS) consists of four WT1-derived peptides which have been chosen to strengthen antigenicity, but also broaden immunogenicity over a wide range of HLA subtypes, being able to stimulate both CD8+ (MHC Class I)- and CD4+ (MHC Class II)-dependent responses. Galinpepimut-S is administered with the adjuvant Montanide and sargramostim (GM-CSF).

Participants who has undergone autologous stem cell transplant (ASCT) will receive vaccinations with GPS every 2 weeks for 10 weeks (a total of 6 vaccinations). Vaccinations will start 12 to 22 days after ASCT. In the absence of disease progression and if clinically stable after the first 6 vaccinations, participants may continue to receive six more vaccinations every month. The use of post-ASCT maintenance therapy with immunomodulatory drugs (IMIDs, eg, thalidomide, lenalidomide) or proteasome inhibitors (PSIs, eg, bortezomib) is allowed from 3 months after transplant.

Eligibility criteria: Inclusion Criteria:

* Symptomatic multiple myeloma, ISS stage 1-3 with confirmed diagnosis of multiple myeloma at MSKCC
* Patients must be eligible to undergo autologous stem cell transplantation by standard institutional criteria
* Patients must have documented WT1 positive disease. For purpose of this study, this is defined as detectable presence of WT1 expression by immunohistochemistry or by WT1 transcript via RT-PCR on a bone marrow or other plasma cell-related biopsy specimen prior to autologous stem cell transplantation. Bone marrow or other biopsy specimen from time of diagnosis from patients diagnosed at MSKCC or outside hospital may be requested for assessment of WT1 expression by IHC
* Age \> or = to 18 years
* Karnofsky performance status \> or = to 50%
* Hematologic parameters:
* Absolute neutrophil count (ANC) \> or = to 1,000/μl
* Platelets \> 50,000/μl
* Biochemical parameters:
* Total bilirubin \< than or = to 2.0 mg/dl
* AST and ALT \< than or = to 2.5 x upper limits of normal (ULN)
* Creatinine \< than or = to 2.0 mg/dl

Exclusion Criteria:

* Pregnant or lactating women
* Patients with active infection requiring systemic antimicrobials
* Patients taking systemic corticosteroids
* Patients with serious unstable medical illness
* Concurrent malignancies

Primary outcomes:
measure: WT1 T-cell Immune Response (IR) 12-14 Weeks After First GPS Administration (6 x Administrations)
timeFrame: 12 weeks after the initial GPS vaccine (end of first series [GPS x 6 administrations])
Secondary outcomes:
measure: Progression-free Survival (PFS) From Autologous Stem Cell Transplant (ASCT)
timeFrame: 3 years and 8 months
measure: Overall Survival (OS) From Autologous Stem Cell Transplant (ASCT)
timeFrame: 3 years and 8 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Miami Cancer Institute (Baptist Health South Florida) - formerly at MSKCC
name: Guenther Koehne, MD, PhD
role: STUDY_DIRECTOR
affiliation: Memorial Sloan Kettering Cancer Center
name: David J Chung, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Koehne G, Devlin S, Korde N, Mailankody S, Landau H, Hassoun H, Lesokhin A, Lendvai N, Chung D, Sarlis N, Giralt S, Landgren O. Galinpepimut-S, a WT1-Targeting Immuno-Oncology Treatment, Induces Specific, Robust and Durable Immune Responses (IRs) in Patients (Pts) with High-Risk (HR) Multiple Myeloma (MM). Clinical Lymphoma, Myeloma and Leukemia 17: S343-S344, 2017