A Study Evaluating the Safety and Efficacy of AUR108 in Patients With Relapsed Advanced Lymphomas (ASHA-1) (ASHA-1)

January 29, 2024 updated by: Aurigene Discovery Technologies Limited

A Phase 1, Open Label, Dose Escalation, Dose Expansion, Multicenter Study Evaluating the Safety, Pharmacokinetics and Pharmacodynamics of Oral AUR108 in Patients With Relapsed Advanced Lymphomas(ASHA-1)

An open-label, first-in-human, Phase 1 study in adult patients with relapsed advanced lymphomas will be done to assess AUR108 safety, tolerability, pharmacokinetics, pharmacodynamics, and optimal biological dose.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a Phase I, Open Label, Dose-Escalation, First-in-Human study in adult patients with select relapsed advanced lymphomas. The safety and tolerability of oral AUR108 will be evaluated in patients with Non-Hodgkin lymphoma and Hodgkin lymphoma who do not have any available curative or life-prolonging treatment options and have exhausted all effective locally available therapies. The traditional 3+3 design for dose escalation will be used to evaluate the safety, pharmacokinetics/pharmacodynamics, and determine the Optimal Biological Dose of AUR108 as a single agent. The Optimal Biological Dose will be selected using a totality of safety, PK, and PD data.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • India
      • Chandigarh, India, 160012
        • Recruiting
        • Post Graduate Institute of Medical Education & Research,
        • Contact:
      • Delhi, India, 110085
        • Recruiting
        • Rajiv Gandhi Cancer Institute And Research Centre
        • Contact:
    • Andhra Pradesh
      • Visakhapatnam, Andhra Pradesh, India, 530040
    • Gujarat
      • Ahmedabad, Gujarat, India, 380015
        • Recruiting
        • HCC Happiness Care and Cure Multispeciality Hospital
        • Contact:
      • Surat, Gujarat, India, 395002
      • Surat, Gujarat, India, 395004
    • Jammu And Kashmir
      • Srinagar, Jammu And Kashmir, India, 190010
        • Recruiting
        • Super Specialty Hospital (G.M.C) Srinagar
        • Contact:
    • Karnataka
      • Belagam, Karnataka, India, 590010
        • Recruiting
        • KLES Dr Prabhakar Kore Hospital and MRC
        • Contact:
    • Kerala
      • Kochi, Kerala, India, 682041
    • Maharashtra
      • Amaravati, Maharashtra, India, 444606
        • Recruiting
        • Sujan Surgical Cancer Hospital And Amravati Cancer Foundation
        • Contact:
      • Kolhapur, Maharashtra, India, 416234
        • Recruiting
        • Kolhapur Cancer Centre
        • Contact:
      • Nagpur, Maharashtra, India, 441108
        • Recruiting
        • All India Institute of Medical Sciences
        • Contact:
      • Nashik, Maharashtra, India, 422002
      • Pune, Maharashtra, India, 411004
        • Recruiting
        • Deenanath Mangeshkar Hospital & Research Center
        • Contact:
    • Maharastra
      • Mumbai, Maharastra, India, 400056
      • Pune, Maharastra, India, 411004
        • Recruiting
        • MTES Sanjeevan Hospital
        • Contact:
    • New Delhi
      • Delhi, New Delhi, India, 10029
        • Recruiting
        • All India Institute of Medical Sciences
        • Contact:
    • Odisha
      • Bhubaneswar, Odisha, India, 751007
        • Recruiting
        • Sparsh Hospital and Critical Care (P) Ltd.
        • Contact:
    • Telangana
      • Hyderabad, Telangana, India, 500004
        • Recruiting
        • MNJ Institute of Oncology and Regional Cancer Centre
        • Contact:
    • West Bengal
      • Kolkata, West Bengal, India, 700160
        • Recruiting
        • Tata Medical Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Males or females ≥ 18 years of age
  2. Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1

  3. Acceptable bone marrow and organ function at screening as described below:

    1. ANC ≥ 1000/μL (without WBC growth factor support)
    2. Platelet count ≥ 75,000/μL without transfusion support
    3. Hemoglobin ≥ 9 g/dL (Transfusion is allowed to achieve this Hb)
    4. Total Bilirubin ≤ 1.5 x ULN; (Patients with known Gilbert's syndrome are allowed with a Total Bilirubin ≤ 2.5 x ULN)
    5. AST (SGOT) ≤ 3 x ULN (≤ 5 × ULN if known liver metastases)
    6. ALT (SGPT) ≤ 3 x ULN (≤ 5 × ULN if known liver metastases)
    7. Creatinine clearance (CrCl) ≥ 30 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)]).
  4. Ability to swallow and retain oral medications
  5. Histo-pathological diagnosis of a Non-Hodgkin lymphoma orHodgkin Lymphoma. Note: The lymphoma should be either in Stage III or IV according to Lugano classification (Cheson BD et al, 2014) at screening.
  6. In the case of subjects who have lymphoma for which high-dose chemotherapy and autologous stem cell transplantation (HDASCT) is considered a standard curative therapy, eligibility for this study requires that the subject's disease has relapsed after HDASCT, that the subject is not eligible for HD-ASCT, or that the subject has refused HD-ASCT.
  7. In the case of subjects who have lymphoma for which CAR-T therapy is considered a standard therapy, eligibility for this study requires that the subjects disease has relapsed after CAR-T, or that the subject has refused CAR-T, or that the CAR-T therapy is not accessible to the patient.
  8. Evidence of measurable disease as per Lugano Criteria for Lymphoma (Cheson BD et al, 2014).

  9. Standard curative measures do not exist, and patient must have exhausted all effective therapies, available locally.

    1. At a minimum, the patients must have received at least 2 prior lines of systemic therapies. These systemic therapies could be either in the stage II, III or IV.
    2. Any cancer patient with access to any effective therapy must not be enrolled.

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 longer, from the Cycle 1 Day 1 of the study.

    Note: Concomitant use of low dose prednisone (up to 10 mg/day) is allowed.

  2. Presence of an acute or chronic toxicity resulting from prior anticancer treatment, with the exception of alopecia or nail changes, that has not resolved to Grade ≤ 1, as determined by NCI CTCAE v 5.0.
  3. 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).
  4. Use of any investigational agent within 28 days or 5 half-lives (whichever is longer) prior to Cycle 1 Day 1.
  5. Patients with cutaneous lymphomas, mycosis fungoides (MF) or Sézary syndrome (SS).
  6. Primary CNS lymphoma
  7. Known symptomatic or untreated or recently treated (≤ 6 months of screening) central nervous system (CNS) lymphoma. Patients with previously treated (> 6 months of screening) CNS lymphoma and are now stable and asymptomatic, from CNS perspective, are allowed
  8. Patients with lymphoma that requires immediate cytoreductive therapy
  9. Patients with lymphoma that requires immediate cytoreductive therapy
  10. Patients on the drugs which are sensitive substrates of CYP2C8 and cannot be discontinued at least one week prior to Cycle 1 Day 1
  11. Patients on the drugs which are sensitive substrates of either Poglycoprotein (P-gp) or breast cancer resistance protein (BCRP) and cannot be discontinued at least one week prior to Cycle 1 Day 1
  12. Major surgery ≤ 28 days from Cycle 1 Day 1 (major surgery is defined as a procedure requiring general anesthesia)
  13. Active infection requiring systemic therapy. Note: Prophylactic use of antibiotics is allowed. Any infection detected during screening period which is resolved adequately according to investigator before the Cycle 1 Day 1, is allowed.
  14. Known to be human immunodeficiency virus (HIV) positive or have an acquired immunodeficiency syndrome-related illness
  15. Known active or chronic hepatitis B (HbsAg +ve) or hepatitis C infection (HCV antibody +ve)
  16. The patient who is expected to require any other form of antineoplastic therapy or targeted therapy while on study.
  17. 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
  18. Ongoing cardiac dysrhythmias requiring treatment of any grade or treatment of cardiac dysrhythmias in past 3 months, before Cycle 1 Day 1.
  19. QTc (Bazzett) interval >460 ms on ECG at screening and/or at Cycle 1 Day 1 pre-dose.
  20. Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or significant gastritis, active bleeding diatheses, presence of any major medical illness (e.g. renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, or psychiatric illness/social situations or clinically significant laboratory / ECG abnormalities at screening, any or a combination of illnesses, which, in the opinion of the PI, may either put the patient at risk because of participation in the study, or influence the results or the patient's ability to participate in the study
  21. Current swab-positive or suspected (under investigation) Covid-19 infection or fever and other signs or symptoms suggestive of Covid-19 infection with recent contact of person(s) with confirmed Covid-19 infection, at screening or Cycle 1 Day 1.
  22. History of another primary malignancy within 5 years prior to starting study drug, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ and the disease under study.
  23. Positive pregnancy test for women of child-bearing potential (WOCBP) at the screening or enrolment visit
  24. Lactating women or WOCBP who are neither surgically sterilized nor willing to use reliable contraceptive methods (hormonal contraceptive, IUD, or any double combination of male or female condom, spermicidal gel, diaphragm, sponge, cervical cap).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: AUR108, 50mg to 300mg
Currently, planned dose levels are 50,90,150,220,300 mg will be administered in 3+/4- regimen.
Drug: AUR108
3 Days dosing, and 4 days no dose in a week

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
1. First cycle Dose Limiting Toxicities (DLT)
Time Frame: 28 Days
Assess dose limiliting toxicities of AUR108
28 Days
Safety of AUR108 as measured by the number of participants with treatment-related adverse events (AE) graded according to NCI CTCAE version 5.0
Time Frame: Through study completion, an average of 1 year
Number of participants with TEAEs
Through study completion, an average of 1 year
Pharmacokinetics Maximum Concentration (Cmax)
Time Frame: Day 1 and Day 17
Maximum Concentration of AUR108
Day 1 and Day 17
Pharmacokinetics: Time to Maximum concentration (Tmax)
Time Frame: Day 1 and Day 17
Tmax in hours
Day 1 and Day 17
Pharmacokinetics: Area under the curve (AUC)
Time Frame: Day 1 and Day 17
Area under the curve (AUC) of AUR108 in h* ng/mL
Day 1 and Day 17
Pharmacokinetics: Terminal elimination half-life
Time Frame: Day 17
Terminal elimination half-life of AUR 108 in hours
Day 17
Maximum concentration (Cmax) administered under fasting/fed condition
Time Frame: Day 8
Compare in fast and fed conditions
Day 8
Time to Maximum concentration (Tmax) administered under fasting/fed condition
Time Frame: Day 8
Compare Tmax in fast and fed conditions
Day 8
Area under curve (AUC) administered under fasting/fed condition
Time Frame: Day 8
Compare AUC in fast and fed conditions
Day 8

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
PD biomarker assessment
Time Frame: Day 1, Day 2, Day 17 and Day 18
Change from baseline in biomarker (DHO) levels
Day 1, Day 2, Day 17 and Day 18
Overall Response Rate
Time Frame: Through study completion, an average of 1 year
Efficacy assessments by Overall Response Rate
Through study completion, an average of 1 year
Duration of Response
Time Frame: Through study completion, an average of 1 year
Efficacy assessments by Duration of Response
Through study completion, an average of 1 year
Progression Free Survival
Time Frame: Through study completion, an average of 1 year
Efficacy assessments by Progression Free Survival (PFS)
Through study completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Aurigene Discovery Technologies Limited

Investigators

  • Principal Investigator: Akhil Kumar, Chief Medical Officer

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 19, 2023

Primary Completion (Estimated)

August 30, 2025

Study Completion (Estimated)

August 30, 2027

Study Registration Dates

First Submitted

July 20, 2023

First Submitted That Met QC Criteria

July 31, 2023

First Posted (Actual)

August 9, 2023

Study Record Updates

Last Update Posted (Estimated)

January 31, 2024

Last Update Submitted That Met QC Criteria

January 29, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AUR108-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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