Clinical trial NCT05475925: A Study of DR-01 in Subjects With Large Granular Lymphocytic Leukemia or Cytotoxic Lymphomas
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: LGLL - Large Granular Lymphocytic Leukemia
Primary Cutaneous Gamma-Delta T-Cell Lymphoma
Primary Cutaneous CD8+ Aggressive Epidermotropic 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
Cytotoxic PTCL-NOS (CD8+ or CD56+ and Cytotoxic Marker)
Cutaneous PTCL-NOS (CD8+ or CD56+ and Cytotoxic Marker)
Keywords: LGLL
Cytotoxic
Lymphoma
ANKL
EATL
MEITL
ENKL
HSTCL
Leukemia
SPTCL
ENKTL
CTCL
PTCL-NOS
TCL
Lead sponsor: Dren Bio
Sponsor class: INDUSTRY
Collaborators: name: Novotech Health Holdings Pte. Ltd.
First posted: 2022-07-27
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria (All Subjects):

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 A only, evaluable disease is acceptable.
12. 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:

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).

Primary outcomes:
measure: Part A: Safety and Tolerability. To determine the incidence and severity of adverse events as assessed by CTCAE v5.0.
timeFrame: Up to 25 months
measure: Part A: Safety and Tolerability. To determine the incidence and severity of dose limiting toxicities (DLTs) as defined by protocol specified DLT criteria.
timeFrame: During First 28 days (Cycle 1)
measure: Part A: To determine potential pharmacologically optimized dose/regimen for DR-01 in LGL leukemia and cytotoxic lymphoma populations as determined using an integrated assessment of efficacy, safety, PK/PD, and exposure-response relationships.
timeFrame: Up to 6 months
measure: 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.
timeFrame: Up to 24 months
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Dren Investigational Site
state: Alabama
city: Duarte
country: United States
facility: Dren Investigational Site
state: California
city: Redwood City
country: United States
facility: Dren Investigational Site
state: California
city: New Haven
country: United States
facility: Dren Investigational Site
state: Connecticut
city: New York
country: United States
facility: Dren Investigational Site 1
state: New York
city: New York
country: United States
facility: Dren Investigational Site 2
state: New York
city: Columbus
country: United States
facility: Dren Investigational Site
state: Ohio
city: Pittsburg
country: United States
facility: Dren Investigational Site 2
state: Pennsylvania
city: Houston
country: United States
facility: Dren Investigational Site
state: Texas
city: Charlottesville
country: United States
facility: Dren Investigational Site
state: Virginia
city: Fairfax
country: United States
facility: Dren Investigational Site
state: Virginia
city: Seattle
country: United States
facility: Dren Investigational Site
state: Washington
city: Clayton
country: Australia
facility: Dren Investigational Site
state: Victoria
city: Richmond
country: Australia
facility: Dren Investigational Site
state: Victoria
city: Nedlands
country: Australia
facility: Dren Investigational Site
state: Western Australia
city: Pierre-Bénite
country: France
facility: Dren Investigational Site
city: Rennes
country: France
facility: Dren Investigational Site
city: Toulouse
country: France
facility: Dren Investigational Site
city: Berlin
country: Germany
facility: Dren Investigational Site
city: Cologne
country: Germany
facility: Dren Investigational Site
city: Leipzig
country: Germany
facility: Dren Investigational Site
city: Hong Kong
country: Hong Kong
facility: Dren Investigational Site 1
city: Hong Kong
country: Hong Kong
facility: Dren Investigational Site 2
city: Bologna
country: Italy
facility: Dren Investigational Site
city: Busan
country: Korea, Republic of
facility: Dren Investigational Site 1
city: Busan
country: Korea, Republic of
facility: Dren Investigational Site 2
city: Goyang-si
country: Korea, Republic of
facility: Dren Investigational Site
city: Seoul
country: Korea, Republic of
facility: Dren Investigational Site 1
city: Seoul
country: Korea, Republic of
facility: Dren Investigational Site 2
city: Seoul
country: Korea, Republic of
facility: Dren Investigational Site 3
city: Barcelona
country: Spain
facility: Dren Investigational Site
city: Salamanca
country: Spain
facility: Dren Investigational Site
city: Tainan
country: Taiwan
facility: Dren Investigational Site
city: Taipei
country: Taiwan
facility: Dren Investigational Site
Study officials:
affiliation: Dren Bio
name: Kimberley Dilley, MD, MPH
role: STUDY_DIRECTOR
References: