Hepatosplenic T-cell Lymphoma Clinical Trial
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
Verified date | October 2023 |
Source | Dren Bio |
Contact | Dren Central Contact |
Phone | 415-737-5277 |
clinops[@]drenbio.com | |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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
Status | Recruiting |
Enrollment | 69 |
Est. completion date | December 2025 |
Est. primary completion date | December 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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). |
Country | Name | City | State |
---|---|---|---|
Australia | Dren Investigational Site | Nedlands | Western Australia |
Australia | Dren Investigational Site | Richmond | Victoria |
France | Dren Investigational Site | Pierre-Bénite | |
France | Dren Investigational Site | Rennes | |
France | Dren Investigational Site | Toulouse | |
Spain | Dren Investigational Site | Barcelona | |
Spain | Dren Investigational Site | Salamanca | |
United States | Dren Investigational Site | Birmingham | Alabama |
United States | Dren Investigational Site | Charlottesville | Virginia |
United States | Dren Investigational Site | Columbus | Ohio |
United States | Dren Investigational Site | Duarte | California |
United States | Dren Investigational Site | Fairfax | Virginia |
United States | Dren Investigational Site | Houston | Texas |
United States | Dren Investigational Site | Jacksonville | Florida |
United States | Dren Investigational Site | New York | New York |
United States | Dren Investigational Site | Philadelphia | Pennsylvania |
United States | Dren Investigational Site | Phoenix | Arizona |
United States | Dren Investigational Site | Redwood City | California |
United States | Dren Investigational Site | Rochester | Minnesota |
United States | Dren Investigational Site | Seattle | Washington |
Lead Sponsor | Collaborator |
---|---|
Dren Bio | Novotech |
United States, Australia, France, Spain,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Part A: Safety and Tolerability. To determine the incidence and severity of adverse events as assessed by CTCAE v5.0. | Up to 25 months | ||
Primary | Part A: Safety and Tolerability. To determine the incidence and severity of dose limiting toxicities (DLTs) as defined by protocol specified DLT criteria. | During First 28 days (Cycle 1) | ||
Primary | 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. | Up to 6 months | ||
Primary | 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. | Up to 24 months |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT02561273 -
Combination Chemotherapy & Lenalidomide in Newly Diagnosed Stage II-IV Peripheral T-cell Non-Hodgkin's Lymphoma
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT02533700 -
CEOP/IVE/GDP Compared With CEOP as the First-line Therapy for Newly Diagnosed Adult Patients With PTCL
|
Phase 2 | |
Completed |
NCT02168140 -
CPI-613 and Bendamustine Hydrochloride in Treating Patients With Relapsed or Refractory T-Cell Non-Hodgkin Lymphoma or Hodgkin Lymphoma
|
Phase 1 | |
Completed |
NCT01427881 -
Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies
|
Phase 2 | |
Completed |
NCT00078858 -
Mycophenolate Mofetil and Cyclosporine in Reducing Graft-Versus-Host Disease in Patients With Hematologic Malignancies or Metastatic Kidney Cancer Undergoing Donor Stem Cell Transplant
|
Phase 1/Phase 2 | |
Completed |
NCT00003196 -
Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed by Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma
|
N/A | |
Terminated |
NCT01678443 -
Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies
|
Phase 1 | |
Terminated |
NCT01408043 -
Etoposide, Filgrastim, and Plerixafor in Improving Stem Cell Mobilization in Treating Patients With Non-Hodgkin Lymphoma
|
N/A | |
Completed |
NCT01466881 -
Alisertib in Treating Patients With Relapsed or Refractory Peripheral T-Cell Non-Hodgkin Lymphoma
|
Phase 2 | |
Completed |
NCT00731536 -
Observational Study on the Occurrence of Hepatosplenic T-cell Lymphoma in Patients of Netherlands
|
Phase 4 | |
Completed |
NCT00608361 -
Dasatinib in Treating Patients With Solid Tumors or Lymphomas That Are Metastatic or Cannot Be Removed By Surgery
|
Phase 1 | |
Completed |
NCT00131937 -
Sorafenib Tosylate in Treating Patients With Recurrent Aggressive Non-Hodgkin's Lymphoma
|
Phase 2 | |
Recruiting |
NCT05377827 -
Dose-Escalation and Dose-Expansion Study to Evaluate the Safety and Tolerability of Anti-CD7 Allogeneic CAR T-Cells (WU-CART-007) in Patients With CD7+ Hematologic Malignancies
|
Phase 1 | |
Withdrawn |
NCT04639843 -
Doxorubicin, CC-(486) (5-azacitidine), Romidepsin, and Duvelisib (hARD) for T-cell Lymphoma
|
Phase 1 | |
Completed |
NCT01254578 -
Lenalidomide After Donor Bone Marrow Transplant in Treating Patients With High-Risk Hematologic Cancers
|
Phase 1 | |
Completed |
NCT01748721 -
MORAb-004 in Treating Young Patients With Recurrent or Refractory Solid Tumors or Lymphoma
|
Phase 1 | |
Completed |
NCT00901147 -
Study of Bortezomib and Panobinostat in Treating Patients With Relapsed/Refractory Peripheral T-cell Lymphoma or NK/T-cell Lymphoma
|
Phase 2 | |
Terminated |
NCT00101205 -
Oxaliplatin, Ifosfamide and Etoposide in Treating Young Patients With Recurrent or Refractory Solid Tumors or Lymphoma
|
Phase 1 | |
Completed |
NCT00040846 -
Alemtuzumab, Fludarabine Phosphate, and Low-Dose Total Body Irradiation Before Donor Stem Cell Transplantation in Treating Patients With Hematological Malignancies
|
Phase 2 | |
Completed |
NCT00112593 -
Fludarabine and Total-Body Irradiation Followed By Donor Stem Cell Transplant and Cyclosporine and Mycophenolate Mofetil in Treating HIV-Positive Patients With or Without Cancer
|
N/A |