Clinical Trials List
Protocol NumberDR-01-ONC-001
NCT Number(ClinicalTrials.gov Identfier)NCT05475925
Active
2023-07-01 - 2027-05-30
Phase I/II
Not yet recruiting2
A Multicenter, Open-Label, First-In-Human, Multiple Expansion Cohort, Phase 1/2 Study to Evaluate the Safety and Efficacy of DR-01 in Adult Subjects With Large Granular Lymphocytic Leukemia or Cytotoxic Lymphomas
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Trial Applicant
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Sponsor
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Wen-Chien Chou Division of Others -
- 田豐銘 Division of General Internal Medicine
- Chien-Chin Lin Division of Others -
- - - Division of General Internal Medicine
- CHENG-HONG TSAI Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- 傅蓓安 Division of General Internal Medicine
- Ya-Ting Hsu Division of General Internal Medicine
- Ya-Ping Chen Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Condition/Disease
large granular lymphocyte
Objectives
The trial will consist of 2 parts: Part A (dose escalation and dose extension) and Part B (cohort expansion). The purpose and evaluation metrics for each part of the trial are detailed below.
Main purpose of Part A:
‧ Evaluating the safety and tolerability of escalating doses of DR-01 in adult subjects with relapsed/refractory LGLL or cytotoxic lymphoma
‧ Determine the potential pharmacologically optimal dose/duration of DR-01 for LGLL and cytotoxic lymphoma populations
Part A Secondary Purpose:
‧ Estimate overall response rate (ORR), complete response (CR) rate, and partial response (PR) rate based on disease-specific response conditions
‧ Estimated response as measured by duration of response (DOR), best overall response (BOR), median progression-free survival (mPFS), overall survival (OS), median OS (mOS) and response time Continuity
‧ Determination of PK profile of DR-01
‧ Evaluate the immunogenicity of DR-01
Part A Exploratory Purpose:
‧ View the PD of DR-01
‧ Examine the release of cytokines in response to DR-01
‧ Assessing molecular CR in T-LGLL
‧ Assessing colonization eradication in chronic lymphoproliferative disease (CLPD)
‧ Use patient self-assessment results (PRO) to evaluate the impact of DR-01 on quality of life (QOL)
‧ Evaluate CD94+ performance
‧ Evaluate disease control rate (DCR)
The main purpose of parts B1 and B2:
‧ Estimate ORR, CR rate and PR rate based on disease-specific response conditions
Secondary purposes of Parts B1 and B2:
‧ Evaluate the safety and tolerability of potentially pharmacologically optimized doses/durations of DR-01 in adult subjects with relapsed/refractory LGLL or cytotoxic lymphoma
‧ Estimate the persistence of response based on DOR, BOR, mPFS, OS, mOS and response time measures
‧ Determination of PK profile of DR-01
‧ Evaluate the immunogenicity of DR-01
Exploratory purpose of Parts B1 and B2:
‧ Examine the PD of DR-01 and its relationship with dose and exposure
‧ Examine the release of cytokines in response to DR-01
‧ Assessing molecular CR in T-LGLL
‧ Assess colonization eradication status in CLPD
‧ Use PRO to evaluate the impact of DR-01 on QOL
‧ Evaluate CD94+ performance
‧ Evaluate DCR
Test Drug
DR-01
Active Ingredient
DR-01
Dosage Form
solution for infusion
Dosage
15mg/ml
Endpoints
‧ Incidence, severity, and relationship of treatment-emergent adverse events (AEs) (including AEs of special interest [AESI] and dose-limiting toxicities [DLT]) and other safety findings
‧ Potential pharmacologically optimal dose/duration of DR-01 in LGLL and cytotoxic lymphoma populations, determined using an integrated assessment of efficacy, safety, PK/PD, and dose-response relationships
‧ Potential pharmacologically optimal dose/duration of DR-01 in LGLL and cytotoxic lymphoma populations, determined using an integrated assessment of efficacy, safety, PK/PD, and dose-response relationships
Inclution Criteria
Inclusion Criteria (All Subjects):
≥18 years of age.
Able to understand and comply with protocol-required study procedures and voluntarily sign a written informed consent document.
Sufficient key organ performance and coagulation.
Female subjects of childbearing potential (postmenarcheal, has an intact uterus and at least one ovary, and is <1 year postmenopausal) must agree to use a highly effective method of contraception from enrollment through at least 12 months after last dose of DR-01.
Male subjects must agree to use acceptable effective method(s) of contraception.
Subjects with LGLL must also meet inclusion criteria 6 and 7.
Must have discontinued at least one prior line of systemic therapy.
Additional immunophenotypic criteria must be met.
Disease-specific Inclusion Criteria (Cytotoxic Lymphomas):
Subjects with cytotoxic lymphomas must also meet inclusion criteria 8,9, and 10.
Subjects must have failed at least two prior systemic regimens.
Availability of post-progression tissue sample or willingness to consent to a baseline biopsy.
Histologically confirmed diagnosis of a cytotoxic lymphoma by a hematopathologist (according to the WHO 2016 classification [Swerdlow 2016]).
For Part A only, evaluable disease is acceptable.
For Part B2 only:
Subjects must have radiographically measurable disease to be assessed by Lugano criteria. Subjects with primary cutaneous variants must have at least 1 measurable lesion that is evaluable using the Olsen criteria (Olsen 2021) or leukemic involvement that can be evaluated using a modified TPLL response criteria (Staber 2019).
Subjects with hepatosplenic disease or other variants that do not have measurable disease by Lugano criteria (Cheson 2014) may be eligible upon discussion with the Medical Monitor if they have identifiable leukemic involvement in BM or peripheral blood (meeting the CD8+ cytotoxic phenotype definition) that can be evaluated for response using a modified TPLL response criteria (Staber 2019), or skin involvement that can be evaluated using Olsen criteria (Olsen 2021).
≥18 years of age.
Able to understand and comply with protocol-required study procedures and voluntarily sign a written informed consent document.
Sufficient key organ performance and coagulation.
Female subjects of childbearing potential (postmenarcheal, has an intact uterus and at least one ovary, and is <1 year postmenopausal) must agree to use a highly effective method of contraception from enrollment through at least 12 months after last dose of DR-01.
Male subjects must agree to use acceptable effective method(s) of contraception.
Subjects with LGLL must also meet inclusion criteria 6 and 7.
Must have discontinued at least one prior line of systemic therapy.
Additional immunophenotypic criteria must be met.
Disease-specific Inclusion Criteria (Cytotoxic Lymphomas):
Subjects with cytotoxic lymphomas must also meet inclusion criteria 8,9, and 10.
Subjects must have failed at least two prior systemic regimens.
Availability of post-progression tissue sample or willingness to consent to a baseline biopsy.
Histologically confirmed diagnosis of a cytotoxic lymphoma by a hematopathologist (according to the WHO 2016 classification [Swerdlow 2016]).
For Part A only, evaluable disease is acceptable.
For Part B2 only:
Subjects must have radiographically measurable disease to be assessed by Lugano criteria. Subjects with primary cutaneous variants must have at least 1 measurable lesion that is evaluable using the Olsen criteria (Olsen 2021) or leukemic involvement that can be evaluated using a modified TPLL response criteria (Staber 2019).
Subjects with hepatosplenic disease or other variants that do not have measurable disease by Lugano criteria (Cheson 2014) may be eligible upon discussion with the Medical Monitor if they have identifiable leukemic involvement in BM or peripheral blood (meeting the CD8+ cytotoxic phenotype definition) that can be evaluated for response using a modified TPLL response criteria (Staber 2019), or skin involvement that can be evaluated using Olsen criteria (Olsen 2021).
Exclusion Criteria
Exclusion Criteria:
Disease-specific Exclusion Criteria; LGLL and ANKL:
A reactive LGL lymphocytosis to a viral infection or LGL associated with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
The following exclusion criteria apply to all subjects:
Active systemic infection or severe localized infection requiring systemic antibiotics, antivirals or antifungals.
Active or suspected malignant central nervous system involvement.
Life-threatening, severe complications of malignancy (e.g., uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation).
Active known second malignancy.
Infection with human immunodeficiency virus (HIV) type 1 or 2 (HIV-1 or HIV-2).
Hepatitis B infection (hepatitis B virus surface antigen [HBsAg] positive), or hepatitis C (hepatitis C virus [HCV] antibody positive, confirmed by HCV ribonucleic acid). Subjects with HCV with undetectable virus after treatment are eligible.
History of clinically significant cardiac disease or congestive heart failure greater than New York Heart Association (NYHA) Class II.
Use of systemic corticosteroids (e.g., >5 mg/day prednisone or equivalent for subjects with LGL leukemia (subjects on 20 mg prednisone or equivalent to treat LGL leukemia must be weaned within 28 days post C1D1 to 5 mg) and >10 mg/day prednisone or equivalent for subjects with cytotoxic lymphoma) within 15 days (except for prophylaxis for radiodiagnostic contrast reactions), or other non-biological immunosuppressive drugs within 15 days, prior to C1D1. Patients on stable prednisone ≤10 mg for documented rheumatologic/autoimmune conditions are exempted from this requirement.
Any condition requiring hormonal therapy (except for contraception, hormone replacement therapy and hormonal prophylaxis for a prior malignancy).
Any other medical or psychiatric condition, or laboratory abnormality that would increase the risk associated with study participation, in the opinion of the Investigator or Medical Monitor.
Toxicities from previous anticancer therapies must have resolved to baseline levels or to Grade 1 (except for alopecia, peripheral neuropathy, or hematologic parameters meeting inclusion criteria).
Autologous HSCT within 40 days of C1D1, allogeneic HSCT within 90 days
Any immunosuppressive therapy for GVHD for subjects who are post allogeneic HSCT.
Major surgery within 28 days of C1D1 (requires more than local anesthesia or plexus blockade).
Disease-specific Exclusion Criteria; LGLL and ANKL:
A reactive LGL lymphocytosis to a viral infection or LGL associated with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
The following exclusion criteria apply to all subjects:
Active systemic infection or severe localized infection requiring systemic antibiotics, antivirals or antifungals.
Active or suspected malignant central nervous system involvement.
Life-threatening, severe complications of malignancy (e.g., uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation).
Active known second malignancy.
Infection with human immunodeficiency virus (HIV) type 1 or 2 (HIV-1 or HIV-2).
Hepatitis B infection (hepatitis B virus surface antigen [HBsAg] positive), or hepatitis C (hepatitis C virus [HCV] antibody positive, confirmed by HCV ribonucleic acid). Subjects with HCV with undetectable virus after treatment are eligible.
History of clinically significant cardiac disease or congestive heart failure greater than New York Heart Association (NYHA) Class II.
Use of systemic corticosteroids (e.g., >5 mg/day prednisone or equivalent for subjects with LGL leukemia (subjects on 20 mg prednisone or equivalent to treat LGL leukemia must be weaned within 28 days post C1D1 to 5 mg) and >10 mg/day prednisone or equivalent for subjects with cytotoxic lymphoma) within 15 days (except for prophylaxis for radiodiagnostic contrast reactions), or other non-biological immunosuppressive drugs within 15 days, prior to C1D1. Patients on stable prednisone ≤10 mg for documented rheumatologic/autoimmune conditions are exempted from this requirement.
Any condition requiring hormonal therapy (except for contraception, hormone replacement therapy and hormonal prophylaxis for a prior malignancy).
Any other medical or psychiatric condition, or laboratory abnormality that would increase the risk associated with study participation, in the opinion of the Investigator or Medical Monitor.
Toxicities from previous anticancer therapies must have resolved to baseline levels or to Grade 1 (except for alopecia, peripheral neuropathy, or hematologic parameters meeting inclusion criteria).
Autologous HSCT within 40 days of C1D1, allogeneic HSCT within 90 days
Any immunosuppressive therapy for GVHD for subjects who are post allogeneic HSCT.
Major surgery within 28 days of C1D1 (requires more than local anesthesia or plexus blockade).
The Estimated Number of Participants
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Taiwan
6 participants
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Global
90 participants
