CTRI/2022/09/046033 [Registered on: 29/09/2022] Trial Registered Prospectively
Last Modified On:
28/09/2022
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Other
Public Title of Study
A Study to check for safety and Efficacy of Galinpepimut-S (GPS) in comparison to Investigators Choice of Best Available Therapy in patients with Acute Myeloid Leukemiaâ€
Scientific Title of Study
A Randomized, Open-Label Study of the Efficacy and Safety of Galinpepimut-S (GPS) Maintenance Monotherapy Compared to Investigators Choice of Best Available Therapy in Subjects with Acute Myeloid Leukemia Who Have Achieved Complete Remission After Second-Line Salvage Therapy
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
2019â€004134â€42
EudraCT
SLSG18-301 version 2.3 dated 05Apr2021
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Designation
Affiliation
Address
Phone
Fax
Email
Details of Contact Person Scientific Query
Name
Rashmi Chitgupi
Designation
Director Clinical Operations
Affiliation
PPD Pharmaceutical Development India Private Limited
Address
101, A wing, Fulcrum, Hiranandani Business Park, Sahar Road, Andheri East,
Mumbai (Suburban)l
India
Mumbai (Suburban) MAHARASHTRA 400099 India
Phone
91-2268804200
Fax
91-2266459321
Email
Rashmi.Chitgupi@ppd.com
Details of Contact Person Public Query
Name
Rashmi Chitgupi
Designation
Director Clinical Operations
Affiliation
PPD Pharmaceutical Development India Private Limited
Address
101, A wing, Fulcrum, Hiranandani Business Park, Sahar Road, Andheri East,
Mumbai (Suburban)l
India
Mumbai (Suburban) MAHARASHTRA 400099 India
Phone
91-2268804200
Fax
91-2266459321
Email
Rashmi.Chitgupi@ppd.com
Source of Monetary or Material Support
Sellas Life Sciences, Times Square Tower 7 Times Square, Suite 2503 New York, NY 10036 USA
Primary Sponsor
Name
Sellas Life Sciences
Address
Times Square Tower 7 Times Square, Suite 2503 New York, NY 10036 USA
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
PPD Pharmaceutical Development India Private Limited
PPD Pharmaceutical Development India Private
Limited, 101, A Wing, Fulcrum, Hiranandani
Business Park Sahar Road, Andheri East,
Mumbai 400099, Maharashtra, India
Countries of Recruitment
Turkey United States of America France Germany Greece Hungary India Italy Poland Russian Federation Serbia Spain Taiwan
Sites of Study
No of Sites = 5
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Sameer Bakhshi
All India Institute of Medical Sciences
Room No. 243, 2nd Floor, Department of Medical Oncology, Dr. BRA Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, Ansari Nagar,110029, India New Delhi DELHI
9958828763
sambakh@hotmail.com
Dr Davinder Paul
Dayanand Medical College and Hospital
First Floor, Research and Development Centre, Tagore Nagar, Civil Lines, Ludhiana- 141001 Ludhiana PUNJAB
9082914447
Davinder5858@gmail.com
Dr Rajesh Kumar Singh
Indira Gandhi Institute of Medical Sciences
Room No.225,Second floor, State Cancer Institute, Indira Gandhi Institute of Medical Sciences, Sheikhpura,800014, ,India Patna BIHAR
8521861068
drrajeshrccigimstrial@gmail.com
Dr Chandran K Nair
Malabar Cancer Centre
Second Floor, Department of Clinical Hematology and Medical Oncology,Malabar Cancer Centre, P. O Moozhikkara, Thalassery,670103, India Kannur KERALA
04902399203
drchandrannair1989@gmail.com
Dr Ganesh S Jaishetwar
Yashoda Hospital
Room no 237,Second floor, Department of Oncology, Raj Bhavan Road, Somajiguda, Hyderabad- 500082, Telangana, India Hyderabad TELANGANA
9966596459
ganeshjaishetwar@gmail.com
Details of Ethics Committee
No of Ethics Committees= 5
Name of Committee
Approval Status
Drug Trial Ethics Committee, Dayanand Medical College and Hospital, Ludhiana
Submittted/Under Review
Institutional Ethics Committee, All India Institute of Medical Sciences
Submittted/Under Review
Institutional Ethics Committee, IEC Malabar Cancer Centre
Approved
Institutional Ethics Committee, Indira Gandhi Institute of Medical Sciences
Submittted/Under Review
Institutional Ethics Committee, Yashoda Academy of Medical Education and Research, Secunderabad
Alexan (Cytarabine) 50 mg/mL Solution for Injection- The shelf life of the product is 2 years and it is stored below 25°C. After dilution in 0.9% sodium chloride solution and 5% glucose solution, chemical and physical stability have been proven for 4 days at a temperature of 2–8ºC, and for 24 hours at a temperature below 25ºC.
Comparator Agent
Best Available Therapy (BAT)
Dacogen (Decitabine) 50 mg Powder for Concentrate for Solution for Infusion- The shelf life of the product is 3 years and it should not be stored above 25°C. The powder should be aseptically reconstituted with 10 ml of water for injections. Upon reconstitution, each ml contains approximately 5 mg of decitabine at pH 6.7 to 7.3. Within 15 minutes of reconstitution, the solution must be further diluted with cold infusion fluids (sodium chloride 9 mg/ml [0.9%] solution for injection or 5% glucose solution for injection) to a final concentration of 0.15 to 1.0 mg/ml. This prepared diluted solution for intravenous
infusion can be stored at 2°C - 8°C for up to a maximum of 3 hours, followed by up to 1 hour at room temperature (20°C - 25°C) before administration.
Comparator Agent
Best Available Therapy (BAT)
Patients on the BAT arm may be treated with:
Four options, as monotherapy or as a combination of the agents listed below, (per treating investigator’s choice):
1. Observation (whereby palliative management with hydroxyurea is allowed), or
2. HMA (decitabine or azacitidine), and/or
3. Venetoclax and/or
4. low-dose ara-C.
Vidaza (Azacitidine) 25 mg/mL Powder for Suspension for Injection- Each vial contains 100 mg azacitidine. The shelf life of the product is 4 years. This medicinal product does not require any special storage conditions. After reconstitution with water, each mL of suspension contains 25 mg azacitidine. When Vidaza is reconstituted using water for injections that has not been refrigerated, chemical and physical in-use stability of the reconstituted medicinal product has been demonstrated at 25 °C for 45 minutes and at 2 °C to 8 °C for 8 hours.
When Vidaza is reconstituted using refrigerated (2 °C to 8 °C) water for injections, the chemical and physical in-use stability of the reconstituted medicinal product has been demonstrated at 2 °C to 8 °C for 22 hours.
Comparator Agent
Best Available Therapy (BAT)
Venclyxto (Venetoclax) 100 mg film-coated tablets- The shelf life of the product is 3 years.
Intervention
Galinpepimut-S
Galinpepimut-S (GPS) is a lyophilized product which, upon reconstitution, produces a solution of 4 different WT1-derived synthetic analog peptides considered as a multicomponent single drug product. Each of the 4 peptides will be supplied at a concentration of 0.2 mg/vial. The peptides include 1 WT1-derivedpeptide (A1) to stimulate CD8+ responses, 2 WT1 long peptides (WT1-427 L, WT1-331 L) to stimulate CD4+ responses, and 1 modified peptide (WT1-122A1 L) that is able to stimulate both CD4+ and CD8+ cells. The WT1-A1 and WT1-122A1 L contain a mutated aminoacid (aa) residue (R126Y), and are, therefore, heteroclitic. The sequence for the heteroclitic WT1-A1peptide is embedded within the sequence of the longer WT1-122A1 L peptide.
The peptides were manufactured at Polypeptide Laboratories, Inc. Sterile fill and finish under Good Manufacturing Practice (GMP) conditions is performed by Corden Pharma.
Intervention
Montanide ISA 51 VG
Montanide ISA 51 VG is an adjuvant (NSC # 737063) produced by SEPPIC, Inc. (Fairfield, NJ) under GMP and is composed of a light oil and a surfactant system designed to make a water-in- oil emulsion. Montanide ISA 51 VG has been clinically tested based on a vegetable grade formulation used to emulsify the peptides. Montanide ISA 51 VG has proved to be a very efficient adjuvant, activating the cellular and the humoral immune response.
Intervention
Sargramostim (GM-CSF)
Sargramostim is a recombinant human GM-CSF produced by recombinant DNA technology in a yeast (S. cerevisiae) expression system. GM-CSF is a hematopoietic growth factor which stimulates proliferation and differentiation of hematopoietic progenitor cells. Sargramostim is manufactured by Partner Therapeutics, Inc. (Lexington, MA), under GMP.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
1. Patients, or their legally acceptable representatives, must be willing and able to understand and provide signed informed consent for the study that fulfills Institution Review Board (IRB) guidelines
2. Male or female patients > 18 years of age on the day of signing informed consent
3. Subjects 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).
4. Subjects must be in second or later morphological complete remission (with or without platelet recovery; CR2/CRp2) for relapsed AML based on the CRp criteria as follows: a. 1000 cells/µL. e. Peripheral blood platelet count >20,000/µL f. absence of extramedullary disease.
5. Patients must have > 800 lymphocytes/ µL.
6. Patients’ leukemic blasts must express WT1 per either IHC or PCR (See APPENDIX 1 and APPENDIX 3)
7. Subjects must not be candidates at the time of study entry for allogeneic stem cell transplant (Allo-SCT) due to intercurrent medical conditions, patient’s preference or lack of an available donor.
8. Subjects must have received the last dose of re-induction antileukemic therapy at least 4 weeks or ten half-lives of induction chemotherapy (whichever is shorter) prior to receiving study treatment.
9. Subjects must be consented within 4 months of having achieved CR2/CRp2 or later.
10. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0,1, 2 or 3 (See APPENDIX 2: ECOG Performance Status)
11. Subjects must have an estimated life expectancy >6 months.
12. If female, is postmenopausal (at least 12 sequential months of amenorrhea) or surgically sterile. Females of childbearing potential must have a negative pregnancy test. 13. 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.
14. Subjects must have 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 >20,000/µL).
15. Subjects must not have end stage renal disease. 16. Subjects must have adequate hepatic function defined as a serum total bilirubin
ExclusionCriteria
Details
1. For subjects randomized to GPS maintenance monotherapy:
a. Continuation of any agents administered as part of induction of CR2/CRp2 or later
b. Receiving any concurrent anti-AML systemic therapy
c. Prior clinically significant allergic reaction to Montanide, sargramostim (GM-CSF) or filgrastim (granulocyte colony stimulating factor [G-CSF]).
d. Received any consolidation and/or maintenance antileukemic therapy, investigational agent, systemic corticosteroid therapy, or other immunosuppressive therapy within 4 weeks prior or 10 half lives, whichever is shorter prior to receiving study treatment. Corticosteroids for chronic conditions (at doses ≤10 mg/day of prednisone or equivalent) are permitted, as are inhalational, intra-ocular, intra articular and topical corticosteroids
2. Subjects with an imminently planned hematopoietic stem cell transplant (autologous or allogeneic, with any degree of match donor).
3. Subjects with acute promyelocytic leukemia or any morphologic and molecular variants, inclusive.
4. Subjects with a serious concurrent illness that in the opinion of the Investigator would pose an undue risk to the subject participating in the clinical study.
5. Subjects who currently have, central nervous system leukemia.
7. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks, or in the case of drugs 10 half lives, whichever is shorter, prior to the first dose of study treatment.
8. Patients who had an SCT after their achieving CR2 or CRp2 or later are not eligible. Patients with prior SCT are allowed only if they had SCT prior to their latest re-induction .
9. Has a 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. Steroids taken as short-term therapy (≤ 7 days) for antiemesis are permissible.
10. Has a known additional malignancy that is progressing or has required active treatment within the past 5 years, even if currently inactive or unapparent.
11. Has known 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.
12. Has known hypersensitivity to Montanide or vaccine adjuvants.
13. Had a previous clinically significant systemic allergic reaction to Montanide, sargramostim (GM-CSF), or filgrastim (G-CSF).
14. Has an 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.
15. Has an active life threatening infection requiring systemic therapy.
16. Has a 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.
17. Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study.
18. Is 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.
19. Has had an allogeneic tissue/solid organ transplant.
20. Has an active Tuberculosis (TB) or latent TB infection.
Method of Generating Random Sequence
Stratified randomization
Method of Concealment
Other
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
The primary objective of the trial is to compare the efficacy of GPS to Investigators choice of BAT on OS in subjects with AML who are in CR2/CRp2.
At day 0, week 2, 4,6,8,10,12,14, 18, 22,26,30,34,40,46,52, End of Treatment, Relapsed, 30d after FU, Long term FU and End of study (GPS arm)
Day 0, week 4, 8,12,14,18,22,26,30,34,40,46,52,EOT,Relapse, LTFU, EOS (BAT arm)
Secondary Outcome
Outcome
TimePoints
To assess the safety & tolerability of GPS as measured by clinical reporting of adverse events, findings on physical exam and laboratory parameters in subjects with AML who are in CR2/CRp2.
• To evaluate the efficacy of GPS compared to Investigators choice of BAT, in subjects with AML who are in CR2/CRp2, with respect to: o Leukemia Free Survival (LFS) o OS rate (%) at 6, 9 and 12 months (landmark) o LFS rate (%) at 6, 9, and 12 months (landmark) o Minimal residual disease by multigene assay (in both peripheral blood and bone marrow aspirates)
Leukemia Free Survival (LFS); 6-, 9-, and 12-month OS; 6-, 9-, and 12-month LFS, and presence of MRD.
6-, 9-, and 12-month OS; 6-, 9-, and 12-month LFS
Target Sample Size
Total Sample Size="116" Sample Size from India="28" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 3
Date of First Enrollment (India)
20/10/2022
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
08/02/2021
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="6" Months="0" Days="0"
Recruitment Status of Trial (Global)
Open to Recruitment
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
NIL
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is an open-label, multicenter, randomized, parallel groups study of Galinpepimut-S (GPS) vs the best available treatment (BAT) in patients with Acute Myeloid Leukemia (AML) in second complete remission (CR2) or in second complete remission with incomplete platelet recovery (CRp2).
All patients will have their historical bone marrow samples and/or peripheral blood samples drawn during screening stained for WT1 via IHC and/or analyzed via PCR 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 about 100 investigational sites. Patients on the BAT arm may be treated with observation (whereby palliative management of leukocytosis with hydroxyurea is allowed), a hypomethylating agent (decitabine or azacitidine), and/or venetoclax and/or low-dose cytarabine (ara-C). Patients whose remission in CR2 that can be maintained with molecularly targeted agents (e.g. FLT-3 or IDH inhibitors) per investigator’s determination will not be eligible. However, there are no restrictions on prior use of any agents in the CR1 setting. Patients can not receive GPS as an adjunct therapy to any other agents. Patients on the GPS arm will receive 70 μg of sargramostim (GM-CSF) on Day -2 as a single injection and on Day 1 30 – 60 minutes 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 be observed for approximately 30 minutes. An End of Treatment visit will be conducted within 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 survival.
The primary objective of the trial is to compare the efficacy of GPS to the Investigator’s choice of BAT on overall survival in subjects with AML who are in CR2/CRp2.