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Trial record 1 of 1 for:    NCT05475925
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A Study of DR-01 in Subjects With Large Granular Lymphocytic Leukemia or Cytotoxic Lymphomas

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ClinicalTrials.gov Identifier: NCT05475925
Recruitment Status : Recruiting
First Posted : July 27, 2022
Last Update Posted : September 8, 2022
Sponsor:
Collaborators:
ProTrials Research Inc.
Novotech
Information provided by (Responsible Party):
Dren Bio

Brief Summary:
This is a multicenter, first-in-human, Phase 1/2 study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and anti-tumor activity of DR-01 in adult patients with large granular lymphocytic leukemia or cytotoxic lymphomas

Condition or disease Intervention/treatment Phase
LGLL - Large Granular Lymphocytic Leukemia Primary Cutaneous T-Cell Lymphoma - Category Primary Cutaneous CD8-Positive Aggressive Epidermotropic T-Cell Lymphoma Primary Cutaneous Acral CD8-Positive T-Cell Lymphoma Hepatosplenic T-cell Lymphoma Subcutaneous Panniculitis-Like T-Cell Lymphoma Aggressive NK Cell Leukemia Systemic EBV1 T-cell Lymphoma, if CD8 Positive Hydroa Vacciniforme-Like Lymphoproliferative Disorder Extranodal NK/T Cell Lymphoma, Nasal Type Enteropathy-Associated T-Cell Lymphoma Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma Indolent Chronic Lymphoproliferative Disorder (CLPD) (CD8+ or NK Derived) of the GI Tract Other CD8+/NK Cell Driven Lymphoma Not Listed Above Drug: DR-01 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 69 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : July 13, 2022
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2025


Arm Intervention/treatment
Experimental: Part A Dose Escalation (Cohort 1) 1 mg/kg of DR-01
Subjects in this arm will initially receive 1 mg/kg every 14 days for the first two doses, followed by monthly dosing (up to 6 mg/kg) thereafter for up to 25 doses total.
Drug: DR-01
DR-01 is a non-fucosylated, human immunoglobulin G1 (IgG1) monoclonal antibody.

Experimental: Part A Dose Escalation (Cohort 2) 3 mg/kg of DR-01
Subjects in this arm will receive initially receive 3 mg/kg every 14 days for the first two doses, followed by monthly dosing (up to 10 mg/kg) thereafter for up to 25 doses total.
Drug: DR-01
DR-01 is a non-fucosylated, human immunoglobulin G1 (IgG1) monoclonal antibody.

Experimental: Part A Dose Escalation (Cohort 3) 6 mg/kg of DR-01
Subjects in this arm will receive initially receive 6 mg/kg every 14 days for the first two doses, followed by monthly dosing (up to 10 mg/kg) thereafter for up to 25 doses total.
Drug: DR-01
DR-01 is a non-fucosylated, human immunoglobulin G1 (IgG1) monoclonal antibody.

Experimental: Part A Dose Escalation (Cohort 4) 10 mg/kg of DR-01
Subjects in this arm will receive initially receive 10 mg/kg every 14 days for the first two doses, followed by monthly dosing (up to 10 mg/kg) thereafter for up to 25 doses total.
Drug: DR-01
DR-01 is a non-fucosylated, human immunoglobulin G1 (IgG1) monoclonal antibody.

Experimental: Part B Dose Expansion (Cohort B1) RP2D of DR-01
Subjects in this arm will receive the recommended Phase 2 dose for LGLL subjects (determined in Part A) every 14 days for the first two doses, followed by monthly dosing thereafter for up to 25 doses total.
Drug: DR-01
DR-01 is a non-fucosylated, human immunoglobulin G1 (IgG1) monoclonal antibody.

Experimental: Part B Dose Expansion (Cohort B2) RP2D of DR-01
Subjects in this arm will receive the recommended Phase 2 dose for cytotoxic lymphoma subjects (determined in Part A) every 14 days for the first two doses, followed by monthly dosing thereafter for up to 25 doses total.
Drug: DR-01
DR-01 is a non-fucosylated, human immunoglobulin G1 (IgG1) monoclonal antibody.

Experimental: Part A Dose De-escalation (Cohort -1) 0.3 to <1 mg/kg of DR-01
This cohort would only be triggered should a DLT occur at Dose Level 1 or if recommended by the Safety Review Committee. Subjects in this arm would initially receive 0.3 to <1 mg/kg every 14 days for the first two doses, followed by monthly dosing (up to 3mg/kg) thereafter for up to 25 doses total.
Drug: DR-01
DR-01 is a non-fucosylated, human immunoglobulin G1 (IgG1) monoclonal antibody.




Primary Outcome Measures :
  1. Part A: Safety and Tolerability. To determine the incidence and severity of adverse events as assessed by CTCAE v5.0. [ Time Frame: Up to 25 months ]
  2. Part A: Safety and Tolerability. To determine the incidence and severity of dose limiting toxicities (DLTs) as defined by protocol specified DLT criteria. [ Time Frame: During First 28 days (Cycle 1) ]
  3. Part A: Max tolerated dose of DR-01 (if applicable). [ Time Frame: Up to 1 month ]
  4. Part A: Recommended Phase 2 dose (RP2D) of DR-01 in LGL leukemia and cytotoxic lymphoma populations as determined by integrated assessment of target engagement/attainment, efficacy, safety, PK/PD, and exposure-response relationships. [ Time Frame: Up to 6 months ]
  5. Part B: Overall Response Rate (ORR), defined as the proportion of subjects with Complete Response (CR) or Partial Response (PR) based on disease-specific response criteria. [ Time Frame: Up to 24 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. ≥18 years of age.
  2. Able to understand and comply with protocol-required study procedures and voluntarily sign a written informed consent document.
  3. Sufficient key organ performance and coagulation.
  4. 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.
  5. Male subjects must agree to use acceptable effective method(s) of contraception.

    Subjects with LGLL must also meet inclusion criteria 6 and 7.

  6. Must have discontinued at least one prior line of systemic therapy.
  7. 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.

  8. Subjects must have failed at least two prior systemic regimens.
  9. Availability of post-progression tissue sample or willingness to consent to a baseline biopsy.
  10. Histologically confirmed diagnosis of a cytotoxic lymphoma by a hematopathologist (according to the WHO 2016 classification [Swerdlow 2016]).
  11. For Part B2: Subjects must have radiographically measurable disease.

Exclusion Criteria:

Disease-specific Exclusion Criteria; LGLL and ANKL:

  1. 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:

  2. Active systemic infection or severe localized infection requiring systemic antibiotics, antivirals or antifungals.
  3. Active or suspected malignant central nervous system involvement.
  4. Life-threatening, severe complications of malignancy (e.g., uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation).
  5. Active known second malignancy.
  6. Infection with human immunodeficiency virus (HIV) type 1 or 2 (HIV-1 or HIV-2).
  7. 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.
  8. History of clinically significant cardiac disease or congestive heart failure greater than New York Heart Association (NYHA) Class II.
  9. 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.
  10. Any condition requiring hormonal therapy (except for contraception, hormone replacement therapy and hormonal prophylaxis for a prior malignancy).
  11. 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.
  12. 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).
  13. Autologous HSCT within 40 days of C1D1, allogeneic HSCT within 90 days
  14. Any immunosuppressive therapy for GVHD for subjects who are post allogeneic HSCT.
  15. Major surgery within 28 days of C1D1 (requires more than local anesthesia or plexus blockade).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05475925


Contacts
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Contact: Dren Central Contact 415-737-5277 clinops@drenbio.com

Locations
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United States, California
Dren Investigational Site Recruiting
Duarte, California, United States, 91010
Contact: Dren Central Contact    415-737-5277      
Dren Investigational Site Not yet recruiting
Redwood City, California, United States, 94063
Contact: Dren Central Contact    415-735-5277      
United States, New York
Dren Investigational Site Not yet recruiting
New York, New York, United States, 10021
Contact: Dren Central Contact    415-735-5277      
United States, Ohio
Dren Investigational Site Not yet recruiting
Columbus, Ohio, United States, 43210
Contact: Dren Central Contact    415-735-5277      
United States, Pennsylvania
Dren Investigational Site Not yet recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Dren Central Contact    415-735-5277      
United States, Texas
Dren Investigational Site Not yet recruiting
Houston, Texas, United States, 77030
Contact: Dren Central Contact    415-737-5277      
United States, Virginia
Dren Investigational Site Not yet recruiting
Charlottesville, Virginia, United States, 22903
Contact: Dren Central Contact    415-735-5277      
Dren Investigational Site Recruiting
Fairfax, Virginia, United States, 22031
Contact: Dren Central Contact    415-737-5277      
Australia, Victoria
Dren Investigational Site Recruiting
Richmond, Victoria, Australia, 3121
Contact: Dren Central Contact    415-735-5277      
Australia, Western Australia
Dren Investigational Site Recruiting
Nedlands, Western Australia, Australia, 6009
Contact: Dren Central Contact    415-735-5277      
Sponsors and Collaborators
Dren Bio
ProTrials Research Inc.
Novotech
Investigators
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Study Director: Matthias Will, MD Dren Bio
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Responsible Party: Dren Bio
ClinicalTrials.gov Identifier: NCT05475925    
Other Study ID Numbers: DR-01-ONC-001
First Posted: July 27, 2022    Key Record Dates
Last Update Posted: September 8, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Dren Bio:
LGLL
Cytotoxic
Lymphoma
ANKL
EATL
MEITL
ENKL
HVLPD
Leukemia
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Leukemia, Lymphoid
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Lymphoma, T-Cell, Cutaneous
Lymphoma, Extranodal NK-T-Cell
Enteropathy-Associated T-Cell Lymphoma
Leukemia, Large Granular Lymphocytic
Lymphoproliferative Disorders
Panniculitis
Hydroa Vacciniforme
Disease
Aggression
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Behavioral Symptoms
Leukemia, T-Cell
Connective Tissue Diseases
Skin Diseases
Photosensitivity Disorders
Skin Diseases, Vesiculobullous