Lymphoma, Large B-Cell, Diffuse Clinical Trial
Official title:
A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of Duvortuxizumab, A Humanized CD19 x CD3 Dual-Affinity Re-Targeting (DART®) Protein in Subjects With Relapsed or Refractory B-cell Malignancies
Verified date | December 2018 |
Source | Janssen Research & Development, LLC |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The purpose of this study is to evaluate the safety, tolerability, dose-limiting toxicities (any harmful effect of a drug) (DLT), maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D) and preliminary clinical activity of duvortuxizumab when administered intravenously to participants with relapsed or refractory B-cell malignancies [diffuse-large B cell lymphoma (DLBCL), follicular lymphoma (FL), mantle-cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), and acute lymphoblastic leukemia (ALL)].
Status | Terminated |
Enrollment | 59 |
Est. completion date | July 26, 2018 |
Est. primary completion date | July 26, 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 - Participants must meet protocol specified hematology and chemistry lab parameters criteria - Histological confirmation of disease with documented disease relapse after the last therapy requiring treatment per the treating physician. Participants with lymphoma must have at least 1 measurable site of disease (Part 2 only). In addition, B-cell malignancy disease-specific criteria specified in the protocol must also be met - A woman of childbearing potential must have a negative highly sensitive serum [beta-human chorionic gonadotropin (ß-hCG)] or urine pregnancy test at (minimum sensitivity 25 International units (IU)/ liter (L) or equivalent units of HCG) within 7 days prior to the first dose of study drug - A woman must agree to use an effective method of birth control and agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 3 months after receiving the last dose of study drug - A man who is sexually active with a woman of childbearing potential must agree to use a barrier method of contraception (eg, condom with spermicidal foam/gel/film/cream/suppository), man who is sexually active with a woman who is pregnant must use a condom and men must agree not to donate sperm for 90 days after the last dose of study drug - Each participant (or their legally acceptable representative) must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study. Consent is to be obtained prior to the initiation of any study related tests or procedures that are not part of standard of care for the participant's disease Exclusion Criteria: - History of, or known central nervous system (CNS) involvement caused by the underlying B-cell malignancy or prior history of National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) Grade greater than or equal to >= 3 drug-related CNS toxicity. Participants with signs or symptoms of CNS involvement should have a computed tomography (CT) or magnetic resonance imaging (MRI) - History of or known or suspected autoimmune disease (exception: vitiligo, resolved childhood atopic dermatitis, and history of Grave's disease that is euthyroid clinically and by laboratory testing at Screening) - Prior allogeneic hematopoietic stem-cell transplant for participants with DLBCL, FL, MCL, and CLL only. Prior allogenic hematopoietic stem-cell transplant is permitted for participants with ALL - Prior solid organ transplantation - Prior treatment with a therapeutic agent targeting CD19 and/or CD3 |
Country | Name | City | State |
---|---|---|---|
n/a |
Lead Sponsor | Collaborator |
---|---|
Janssen Research & Development, LLC |
United States, Belgium, France, Israel, Spain,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Part 1: Recommended Phase 2 Dose (RP2D) of Duvortuxizumab | The RP2D will be determined based on safety, clinical activity, pharmacokinetics, and pharmacodynamics in participants with relapsed or refractory B cell malignancies [diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL)]. | Approximately 15 months | |
Primary | Part 2: Number of Participants With Overall Response Rate (ORR) | The ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR) per criteria for response assessment of Non Hodgkin Lymphomas (NHL) or International Workshop on Chronic Lymphocytic Leukemia (IWCLL), or complete response (CR), complete response with partial hematologic recovery (CRp), or complete response with incomplete recovery of counts (CRi) per response criteria for acute lymphoblastic leukemia (ALL). | Approximately 2 Years | |
Secondary | Part 1 and 2: Area Under the Curve From Time Zero to End of Dosing Interval (AUC tau) of Duvortuxizumab | The AUC tau is the area under the serum concentration versus time curve during a dose interval time period (tau). | Approximately 2 Years | |
Secondary | Part 1 and 2: Maximum Serum Concentration (Cmax) of Duvortuxizumab | The Cmax is the maximum observed serum concentration of duvortuxizumab. | Approximately 2 Years | |
Secondary | Part 1 and 2: Half-Life (t1/2) of Duvortuxizumab | The t(1/2) is defined as 0.693/Lambda (z) | Approximately 2 Years | |
Secondary | Part 1 and 2: Total Systemic Clearance (CL) of Duvortuxizumab | The CL is a quantitative measure of the rate at which a drug substance is removed from the body. | Approximately 2 Years | |
Secondary | Part 1 and 2: Volume of Distribution at Steady-State (Vss) of Duvortuxizumab | The Vss is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of duvortuxizumab at steady state. | Approximately 2 Years | |
Secondary | Part 1 and 2: Immunogenicity of Duvortuxizumab | Plasma levels of antibodies to duvortuxizumab for evaluation of potential immunogenicity. | Approximately 2 Years | |
Secondary | Part 2: Duration of Response (DoR) | The DoR is defined as the time from the first observed response (CR or PR) to documented disease progression or death due to any cause. | Approximately 2 Years | |
Secondary | Part 2: Progression Free Survival (PFS) for DLBCL, FL, MCL, and CLL | The PFS is defined as the time from date of the first dose of study drug to documented disease progression or death due to any cause. | Approximately 2 Years | |
Secondary | Part 2: Percentage of Participants With Complete Response (CR) | The CR is defined as a best response of CR according to the Criteria for Response Assessment of Non-Hodgkin Lymphomas (NHL), International Workshop on Chronic Lymphocytic Leukemia (CLL) or Response Criteria for acute lymphoblastic leukemia (ALL). | Approximately 2 Years | |
Secondary | Part 2: Percentage of Participants with Overall Survival | Overall survival is defined as the duration from the date of the first dose of the study drug to the date of death for DLBCL, FL, MCL, CLL, and ALL. | Up to followup (Approximately 2 Years) | |
Secondary | Part 1 and 2: Number of Participants with Adverse Events (AEs) and Serious AEs | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. | Screening up to follow-up (Approximately 2 Years) | |
Secondary | Part 2: Relapse-Free survival for Acute Lymphoblastic Leukemia (RFS for ALL) | Relapse free survival (RFS) is defined as time from the date of the first dose of the study drug to relapse from CR, progressive disease, or death due to any cause for ALL. | Approximately 2 Years |
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