Trial Title:
A First in Human Study of AUR 103 Calcium to Evaluate Safety, Pharmacokinetics and Pharmacodynamics
NCT ID:
NCT05607199
Condition:
Solid Tumor, Adult
Acute Myeloid Leukemia
Myelodysplastic Syndromes
Non Hodgkin Lymphoma
Conditions: Official terms:
Myelodysplastic Syndromes
Calcium
Conditions: Keywords:
CD 47 inhibitor
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Intervention model description:
Dose Escalation "3+3" Design
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
AUR103
Description:
Twice Daily
Arm group label:
AUR103, 25mg to 400mg
Other name:
AUR 103 Calcium
Summary:
A Phase I, Open Label, Dose-Escalation, First in Human (FIH) study evaluating the Safety,
Pharmacokinetics, Pharmacodynamics and Efficacy of AUR103 Calcium in patients with
relapsed advanced malignancies (BHARAT-1).
Detailed description:
This is a three-part (Part 1, Part 2A / 2B and Part 3A / 3B) Phase I, open-label,
multi-center trial. In Part 1, the safety and tolerability of oral AUR103 Calcium will be
evaluated among patients with advanced solid tumors who do not have any available
curative or life prolonging treatment options and have exhausted all effective locally
available therapies. In Part 2A, the safety and tolerability of oral AUR103 Calcium will
be assessed in combination with Azacitidine in patients with AML / MDS. Thereafter,
efficacy of the combination of AUR103 Calcium and Azacitidine will be assessed in AML /
MDS in Part 2B. In Part 3A, the safety and tolerability of oral AUR103 Calcium will be
assessed in combination with Rituximab in patients with NHL. Thereafter, efficacy of the
combination of AUR103 Calcium and Rituximab will be assessed in NHL in Part 3B.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Provide signed and dated informed consent and agree to comply with all study related
activities.
2. Male or female patients aged ≥ 18 years.
3. Patients have to meet the following criteria for each of the respective parts of the
study:
Part 1:
Pathological diagnosis of a solid tumor. Standard curative or life prolonging
measures do not exist and patient must have exhausted all effective therapies,
available locally. At a minimum, patients should have received at least 2 lines of
therapy in the metastatic setting.
Part 2A and 2B:
Diagnosis of Acute myeloid leukemia (AML) according to the World Health Organization
(WHO 2016, Appendix B) criteria. OR Myelodysplastic syndrome (MDS) according to the
WHO classification (WHO 2016, Appendix B). Patients with relapsed / refractory AML
(patients should have received at least one line of previous therapy and be eligible
for single agent Azacitidine) or Intermediate / High-Risk / Very High-Risk
Myelodysplastic syndrome (MDS) with IPSS-R score greater than 3.5, by IPSS - R
criterion (Appendix C) who are eligible to receive AZA.
Part 3A and 3B:
Patients of CD20+ B cell NHL, who are refractory or relapsed after at least two
previous lines of therapy Patients must not have any curative or life prolonging
option and must not require immediate cytoreductive therapy Patients with
histological sub-types of follicular lymphoma, marginal zone lymphoma (includes
nodal marginal zone, splenic marginal zone and extra-nodal marginal zone of MALT
tissue), mantle cell lymphoma, diffuse large B cell lymphoma, histologically
transformed indolent lymphomas to DLBCL, high-grade B cell lymphomas and Primary
Mediastinal Large B cell Lymphoma.
Patients with indolent lymphomas (e.g., follicular lymphoma, marginal zone lymphoma
or mantle cell lymphoma) must have conventional criterion, such as GELF criterion14
, for requiring treatment Single agent Rituximab is a viable treatment alternative
for the patient. Please refer to Appendix F for a detailed list of drugs/previous
treatments. Note: The list is not exhaustive and not every treatment may be
available locally.
Patients with respective NHL subtypes should have received the following treatments
Sub-Type of CD20+ B Cell Lymphoma : Follicular Lymphoma
Previous Treatments :
Patient must have received treatment with chemotherapy and CD20 antibody previously
Patients must have received at least two lines of therapy previously and be eligible
to receive Rituximab Sub-Type of CD20+ B Cell Lymphoma : Nodal Marginal Zone
Lymphoma or Splenic Marginal Zone Lymphoma
Previous Treatments:
Patient must have received treatment with chemotherapy and CD20 antibody previously
Patient must have received BTK inhibitors and PI3K inhibitors, unless not available
locally to the patient Patient must have received at least two lines of therapy
previously and be eligible to receive Rituximab Sub-Type of CD20+ B Cell Lymphoma:
Extra nodal Marginal Zone Lymphoma of MALT tissue
Previous Treatments:
Patient must have received treatment with accepted antibiotic therapy for H. Pylori
as well as chemotherapy and CD20 antibody previously Patient must have received BTK
inhibitors and PI3K inhibitors, unless not available locally to the patient Patient
must have received at least two lines of therapy previously Sub-Type of CD20+ B Cell
Lymphoma: Diffuse Large B Cell Lymphoma or Histologically transformed indolent
lymphomas to DLBCL or High-grade B cell lymphomas
Previous Treatments:
Patient must have received treatment with R-CHOP / R-CVP (if not eligible for
doxorubicin) Patient must have received High Dose Chemotherapy with Autologous Stem
Cell Transplant, unless patient is not eligible or has refused transplant previously
Patient must have received at least two lines of therapy previously Sub-Type of
CD20+ B Cell Lymphoma: Mantle Cell Lymphoma
Previous Treatments:
Patient must have received treatment with chemotherapy and CD20 antibody previously
Patient must have received BTK inhibitors unless not available locally to the
patient Patient must have received High Dose Chemotherapy with Autologous Stem Cell
Transplant, unless patient is not eligible or has refused transplant previously
Patient must have received at least two lines of therapy previously
4. Eastern Cooperative Oncology Group (ECOG) (Appendix D) Performance status of 0 or 1
(Patients with disease related ECOG 2 are allowed, in addition to ECOG 0 and 1).
5. Acceptable bone marrow as described below:
Part 1 ANC greater than1500/μL (without WBC growth factor support). Platelet count
greater than100,000/μL without transfusion support. Hemoglobin greater than 9 g/dL
(Transfusion is allowed to achieve this Hb). Part 2A and 2B WBC Less than 20,000/μL
(Hydroxyurea can be given to reduce WBC count to Less than 20,000/μl). Platelet
count greater than 50,000/μL without transfusion support. Hemoglobin greater than 9
g/dL (Transfusion is allowed to achieve this Hb). Part 3A and 3BANCgreater than 1000
/ μL. Platelet count greater than 50,000/μL without transfusion support. Hemoglobin
greater than9 g/dL (Transfusion is allowed to achieve this Hb).
6. Acceptable organ function as described below:
Total Bilirubin less than 1.5 x ULN; (Patients with known Gilbert's syndrome are
allowed with a Total Bilirubin Less than 2.5 x ULN). AST (SGOT) Less Than 3 x ULN
(Less than 5 × ULN if known liver metastases). ALT (SGPT) Less than 3 x ULN (less
than 5 × ULN if known liver metastases). Creatinine clearance (CrCl) greater than 60
mL/min (either measured or estimated by the Cockcroft-Gault formula).
(Cockcroft-Gault formula for estimated creatinine clearance [eCrCl]: eCrCl = [140 -
Age] × Weight [kg] × [0.85 if Female] / [72 × serum creatinine (mg/dL)]). Albumin
greater than 3.0 g/dL
7. Ability to swallow and retain oral medications.
8. Negative serum pregnancy test in women of childbearing potential (WOCBP).
9. Women of childbearing potential and men who partner with such a woman of
childbearing potential must agree to use one or more of highly effective method(s)
for contraception for the duration of the study, i.e.,through 28-day follow up
visit, after discontinuation of study drug(s).
10. Evidence of measurable disease per RECIST, v1.1 for solid tumors (Eisenhauer et al.
2009, Appendix E) and per Lugano Criteria for Lymphoma (Cheson et al. 2014, Appendix
J). Measurable disease for solid tumors is defined as at least one lesion that can
be accurately measured in at least 1 dimension with a minimum size of 10 mm for
non-nodal lesions or 15 mm in short axis for nodal lesions. For malignant lymphomas,
measurable disease is defined as a lesion that can be accurately measured with a
minimum size of 10 mm in both dimensions or 15 mm in greatest transverse diameter.
AML/MDS patients are per WHO 2016 criterion.
Exclusion Criteria:
1. Systemic anti-cancer therapy, such as chemotherapy, or biological therapy,
immunomodulatory drug therapy, received within the past 28 days or 5 half-lives,
whichever is shorter, from the Cycle 1 Day 1 of the study. Concomitant use of
prednisone or medroxyprogesterone is allowed. In Part 1, Patients with CRPC
(castrate resistant prostate cancer) should continue to receive ongoing medical
castration with LHRH analogues, and such patients are allowed.
2. Acute promyelocytic leukemia (AML M3 subtype).
3. Patients eligible for intensive chemotherapy for AML (such as the 3 + 7 regimen).
4. CML in blast crisis (i.e., patients with known bcr-abl positive disease).
5. Presence of an acute or chronic toxicity resulting from prior anti cancer treatment,
with the exception of alopecia or nail changes, that has not resolved to Grade Less
than 1, as determined by NCI CTCAE v 5.0 (Appendix G).
6. Definitive Radiotherapy within the last 21 days of Cycle 1 Day 1 (limited field
palliative radiation is allowed and no restrictions during the screening period or
during the trial).
7. Use of any investigational agent within 28 days or 5 half-lives (whichever is
shorter) prior to Cycle 1 Day 1.
8. Known symptomatic or untreated or recently treated (Less than 6 months of screening)
central nervous system (CNS) metastases or CNS lymphoma or CNS leukemia. Patients
with previously treated (greater than 6 months of screening) CNS metastases or CNS
lymphoma or CNS leukemia and are now stable and asymptomatic, from CNS perspective,
are allowed.
9. Major surgery Less than 28 days from Cycle 1 Day 1 (major surgery is defined as a
procedure requiring general anesthesia).
10. Known to be human immunodeficiency virus (HIV) positive or have an acquired
immunodeficiency syndrome-related illness.
11. Known active or chronic hepatitis B or hepatitis C infection.
12. Uncontrolled congestive heart failure (New York Heart Association [NYHA] Class 2-4),
angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery
bypass graft surgery, or transient ischemic attack, or pulmonary embolism within 3
months prior to Cycle 1 Day 1
13. Ongoing cardiac dysrhythmias requiring treatment of any gradeor treatment of cardiac
dysrhythmias in past 3 months, before Cycle 1 Day 1.
14. The QTcF (corrected QT interval Fridericia method) value in the screening ECG
greater than 450 ms in males and greater than 460 ms in females.
15. Previous allogeneic stem cell or bone marrow transplantation
16. NHL subtypes of Burkitt Lymphoma, Lymphoblastic Lymphoma, AIDS related lymphoma,
Primary CNS Lymphoma, Waldenstrom Macroglobulinemia, Castleman Disease, Post
Transplant Lymphoproliferative Disorder and anaplastic large B cell lymphoma.
17. Previous or concomitant additional malignancy, except for basal-cell or squamous
cell carcinoma of the skin or carcinoma in-situ of the uterine cervix; patients with
other malignancies are eligible if they have remained disease free for at least 2
years prior to trial entry and in the opinion of the investigator deemed to have a
low likelihood of recurrence.
18. Pregnant or lactating women.
19. Any clinically significant medical, psychiatric or social condition; or laboratory
abnormality that may increase the risk of trial participation or may interfere with
the informed consent process and/or with compliance with the requirements of the
trial or may interfere with the interpretation of the trial results and, in the
Investigator's opinion, would make the patient inappropriate for entry into this
trial.
Gender:
All
Minimum age:
18 Years
Maximum age:
99 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Unique Hospital
Address:
City:
Surat
Zip:
395002
Country:
India
Status:
Recruiting
Contact:
Last name:
Dr. Ankit Patel
Phone:
9825404202
Email:
drankitoncologist@gmail.com
Facility:
Name:
Kiran Multi Super Specialty Hospital
Address:
City:
Surat
Zip:
395004
Country:
India
Status:
Recruiting
Contact:
Last name:
Dr. Anshul Agarwal
Phone:
8657068668
Email:
anshul.onco@gmail.com
Facility:
Name:
K R Hospital
Address:
City:
Mysore
Zip:
570001
Country:
India
Status:
Recruiting
Contact:
Last name:
Dr. Mukesh S
Phone:
9886873788
Email:
dal_muk1@hotmail.com
Facility:
Name:
Grant Medical Foundation Ruby Hall Clinic
Address:
City:
Pune
Zip:
411001
Country:
India
Status:
Recruiting
Contact:
Last name:
Dr. Minish Jain
Phone:
9823133390
Email:
minishjain009@gmail.com
Facility:
Name:
All India Institute of Medical Sciences
Address:
City:
Delhi
Zip:
10029
Country:
India
Status:
Recruiting
Contact:
Last name:
Dr. Deepam Pushpam
Phone:
9650629370
Email:
deepampushpam@gmail.com
Start date:
September 16, 2022
Completion date:
October 16, 2026
Lead sponsor:
Agency:
Aurigene Discovery Technologies Limited
Agency class:
Industry
Source:
Aurigene Discovery Technologies Limited
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05607199
