Clinical Trials /

GPS Compared With BAT in AML CR2/CR2p

NCT04229979

Description:

To assess the safety and efficacy of galinpepimut-S compared with investigator's choice of best available therapy (BAT) on overall survival (OS) in subjects with acute myeloid leukemia (AML) who are in second complete remission 2 (CR2)/second complete remission with incomplete platelet recovery (CR2p).

Related Conditions:
  • Acute Myeloid Leukemia
  • Secondary Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: GPS Compared With BAT in AML CR2/CR2p
  • Official Title: Randomized, Open-Label Study of the Efficacy and Safety of Galinpepimut-S Maintenance Therapy Compared to Best Available Therapy in Acute Myeloid Leukemia Patients Who Have Achieved Complete Remission After Second-Line Salvage Therapy

Clinical Trial IDs

  • ORG STUDY ID: SLSG18-301
  • NCT ID: NCT04229979

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
Galinpepimut-SSLS-001Galinpepimut-S
Best Available TherapyInvestigator's choice: observation OR [decitabine or azacitidine] OR venetoclax OR low-dose cytarabine)Best Available Therapy

Purpose

To assess the safety and efficacy of galinpepimut-S compared with investigator's choice of best available therapy (BAT) on overall survival (OS) in subjects with acute myeloid leukemia (AML) who are in second complete remission 2 (CR2)/second complete remission with incomplete platelet recovery (CR2p).

Detailed Description

      This is an open-label, multicenter, randomized, parallel groups study of GPS vs. best
      available treatment (BAT) in patients with AML in second complete remission (CR2) or in
      second complete remission with incomplete platelet recovery (CRp2). All patients will have
      bone marrow samples stained for WT1 via IHC by central pathology review. The primary goal of
      the study will be to demonstrate an advantage for GPS in overall survival in these patient
      populations. The study will enroll approximately 116 patients and will be conducted at up to
      50 investigational sites. Patients will be randomized 1:1 to GPS or BAT stratified by whether
      they are in CR2 or CRp2.

      Patients on the BAT arm may be treated with 1. observation (whereby palliative management
      with hydroxyurea is allowed), 2. a hypomethylating agent (decitabine or azacitidine), 3.
      Venetoclax monotherapy or 4. low-dose ara-C monotherapy. Patients whose remission is
      maintained with other agents (e.g. FLT-3 or IDH inhibitors) will not be eligible.

      Patients on the GPS arm will receive 70 μg of sargramostim (GM- CSF) on Day -2 and Day 1
      before each injection of GPS. The first two administrations of GM-CSF will take place at the
      same anatomical site as the planned administration of GPS within each treatment cycle. GPS
      will be administered as an immunization induction every 2 weeks for 6 administrations (Weeks
      0 - 10); this will be followed by a 4-week period of no treatment. Treatment will then resume
      for 6 administrations as an initial booster phase every 4 weeks (Weeks 14 - 34) which will
      again be followed by a period of no treatment lasting 6 weeks. GPS will be resumed after this
      period as a second booster phase and will be administered every 6 weeks for 3 administrations
      (Weeks 40 - 52). Following each administration of GM-CSF or GPS, patients will remain in the
      clinic for approximately 30 minutes for observation. An End of Treatment visit will be
      conducted 30 days following the last dose of GPS. Patients will then enter the long-term
      follow-up portion of the trial where they will be followed for recurrence of leukemia and
      overall survival.
    

Trial Arms

NameTypeDescriptionInterventions
Galinpepimut-SExperimentalA maximum of 15 total injections will be administered as follows: First 6 galinpepimut-S injections: every 2 weeks (Weeks 0 - 10) followed by a 4-week period of no treatment. The first series of 6 injections of galinpepimut-S define the initial immunization induction phase. Injections 7-12: every 4 weeks (between Weeks 14 and 34) followed by a 6-week period of no treatment. The second series of injections of galinpepimut-S define the early immune booster phase. Injections 13 to 15: every 6 weeks (between Weeks 40 and 52). The third series of injections of galinpepimut-S define the late immune booster phase.
  • Galinpepimut-S
Best Available TherapyActive ComparatorFour options (per treating investigator's choice): Observation (whereby palliative management with hydroxyurea is allowed), or HMA (decitabine or azacitidine) monotherapy, or Venetoclax monotherapy, or Low-Dose Ara-C
  • Best Available Therapy

Eligibility Criteria

        Inclusion Criteria:

          -  Willing and able to understand and provide signed informed consent for the study that
             fulfills Institution Review Board (IRB) guidelines

          -  Male or female patients > 18 years of age on the day of signing informed consent

          -  Must have a diagnosis of AML according to the WHO criteria (primary/de novo or
             secondary, including treatment-related [e.g., due to prior anthracycline use], as well
             as cases due to progression of antecedent hematological disorder [e.g., MDS, MPN, or
             MDS/MPN 'overlap' syndrome).

          -  Must be in second morphological complete remission (with or without platelet recovery;
             CR2/CR2p) for relapsed (but not refractory AML) based upon the International Working
             Group (IWG) 2003 criteria as follows:

               -  <5% myeloblasts in bone marrow.

               -  Absence of circulating peripheral blasts.

               -  Peripheral blood absolute neutrophil count (ANC) >1000 cells/µL. d. Peripheral
                  blood platelet count >60,000/µL

               -  absence of extramedullary disease.

          -  Leukemic blasts must express WT1

          -  Free of any requirement for red blood cell transfusions.

          -  Are not candidates at the time of study entry for allogeneic stem cell transplant
             (Allo-SCT) due to intercurrent medical conditions or lack of an available donor.

          -  Received the last dose of antileukemic therapy at least 3 months prior to study
             enrolment.

          -  Must be within 3 months of having achieved CR2/CR2p

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

          -  Estimated life expectancy >6 months.

          -  If female, is postmenopausal (at least 12 sequential months of amenorrhea) or
             surgically sterile.

          -  Females of childbearing potential must have a negative pregnancy test

          -  Female patients of childbearing potential who are heterosexually active and male
             patients with female sexual partners of childbearing potential must agree to use an
             effective method of contraception (e.g., oral contraceptives, double-barrier methods
             such as a condom and a diaphragm, intrauterine device) during the study and for 4
             months following the last dose of study medication, or to abstain from sexual
             intercourse for this time; a woman not of childbearing potential is one who has
             undergone bilateral oophorectomies or who is post- menopausal, defined as the absence
             of menstrual periods for 12 consecutive months.

          -  Recovered to National Cancer Institute Common Terminology Criteria for Adverse Events
             (CTCAE) v5 Grade 0 or 1 after completion of prior AML therapy with the exception of
             the platelet count requirements (i.e., as long as peripheral blood platelet count is
             >60,000/µL).

          -  Adequate renal function defined as a serum creatinine <2 × upper limit of normal (ULN)
             or calculated creatinine clearance > 30 mL/min based on the Cockroft-Gault equation.

          -  Adequate hepatic function defined as a serum total bilirubin <2 × ULN (except for
             Gilbert's syndrome, which will allow bilirubin ≤3.0 mg/dL), and alanine
             aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × ULN.

          -  Willing and able to return to the clinical site for adequate follow-up and to comply
             with the protocol as required.

        Exclusion Criteria:

          -  For subjects randomized to GPS maintenance monotherapy:

               -  Continuation of any agents administered as part of induction of CR2/CR2p

               -  Receiving any concurrent anti-AML systemic therapy

               -  Prior clinically significant allergic reaction to Montanide, sargramostim
                  (GM-CSF) or filgrastim (granulocyte colony stimulating factor [G-CSF]).

               -  Received any investigational agent, systemic corticosteroid therapy, or other
                  immunosuppressive therapy within 4 weeks prior to enrolment within the study.
                  Corticosteroids for chronic conditions (at doses ≤7.5 mg/day of prednisone or
                  equivalent) or permitted, as are inhalational, intra-ocular, intra-articular and
                  topical corticosteroids.

          -  Complete remission with incomplete hematologic recovery (CRi).

          -  Complete remission with partial haematologic recovery (CRh).

          -  Imminently planned hematopoietic stem cell transplant (autologous or allogeneic, with
             any degree of match donor).

          -  Acute promyelocytic leukemia or any morphologic and molecular variants, inclusive.

          -  Serious concurrent illness that in the opinion of the Investigator would pose an undue
             risk to the subject being participating in the clinical study.

          -  History of, or who currently have, central nervous system leukemia.

          -  Received a live vaccine within 30 days prior to the first dose of study drug.

          -  Currently participating in or has participated in a study of an investigational agent
             or has used an investigational device within 4 weeks prior to the first dose of study
             treatment.

          -  Undergone prior allogeneic hematopoietic stem cell transplantation

          -  Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in
             dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
             immunosuppressive therapy within 7 days prior the first dose of study drug. The use of
             physiologic doses of corticosteroids may be approved after consultation with the
             Sponsor.

          -  Additional malignancy that is progressing or has required active treatment within the
             past 5 years, even if currently inactive or unapparent.

          -  Active CNS metastases and/or carcinomatous meningitis. Participants with previously
             treated brain metastases may participate provided they are radiologically stable,
             i.e., without evidence of progression for at least 4 weeks by repeat imaging (note
             that the repeat imaging should be performed during study screening), clinically stable
             and without requirement of steroid treatment for at least 14 days prior to first dose
             of study treatment.

          -  Hypersensitivity to Montanide or vaccine adjuvants.

          -  Previous clinically significant systemic allergic reaction to Montanide, sargramostim
             (GM-CSF), or filgrastim (G-CSF).

          -  Active autoimmune disease that has required systemic treatment in past 2 years (i.e.,
             with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
             Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
             replacement therapy for adrenal or pituitary insufficiency) is not considered a form
             of systemic treatment and is allowed.

          -  Active infection requiring systemic therapy.

          -  History or current evidence of any condition, therapy, or laboratory abnormality that
             might confound the results of the study, interfere with the patient's participation
             for the full duration of the study, or is not in the best interest of the participant
             to participate, in the opinion of the treating investigator. This includes any
             serious, intercurrent, chronic, or acute illness, such as cardiac disease (New York
             Heart Association [NYHA] class III or IV), hepatic disease, or other illness
             considered by the investigator as an unwarranted high risk for investigational drug
             treatment.20.Has a known psychiatric or substance abuse disorder that would interfere
             with the participant's ability to cooperate with the requirements of the study.

          -  Pregnant or breastfeeding or expecting to conceive or father children within the
             projected duration of the study, starting with the screening visit through 30 days
             after the last dose of study treatment.

          -  Had an allogeneic tissue/solid organ transplant.

          -  Received transfusion of blood products (including platelets or red blood cells) or
             administration of colony stimulating factors (excluding GM-CSF, but including G CSF or
             recombinant erythropoietin) within 4 weeks prior to first study treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival
Time Frame:Up to 52 weeks
Safety Issue:
Description:The primary objective of the trial is to compare the efficacy of GPS to Investigator's choice of BAT on OS in subjects with AML who are in CR2/CR2p.

Secondary Outcome Measures

Measure:LFS
Time Frame:at 6, 9, and 12 months
Safety Issue:
Description:Leukemia Free Survival
Measure:OS rate (%)
Time Frame:At 6, 9 and 12 months
Safety Issue:
Description:Percentage of patients surviving
Measure:LFS rate (%)
Time Frame:At 6, 9, and 12 months
Safety Issue:
Description:Percentage of patients surviving and being free of leukemic relapse
Measure:MRD
Time Frame:Up to 52 weeks
Safety Issue:
Description:Minimum residual disease by multigene assay

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sellas Life Sciences Group

Last Updated

January 18, 2020