Study Stopped
Request by sponsor due to no enrollment of participants on study
Trabectedin and Venetoclax in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Resistant or Intolerant to a BTK Inhibitor
A Phase I/Ib Pilot Study of Combined Trabectedin and Venetoclax in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Resistant or Intolerant to a BTK Inhibitor
3 other identifiers
interventional
N/A
1 country
1
Brief Summary
This phase I/Ib trial studies the best dose and side effects of trabectedin and venetoclax in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma that is resistant or intolerant to a BTK inhibitor. Drugs used in chemotherapy, such as trabectedin and venetoclax, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
Trial Health
Trial Health Score
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Started Jun 2019
1 active site
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Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 19, 2019
CompletedFirst Posted
Study publicly available on registry
March 21, 2019
CompletedStudy Start
First participant enrolled
June 18, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 4, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
March 4, 2020
CompletedSeptember 25, 2023
September 1, 2023
9 months
March 19, 2019
September 21, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
Dose and schedule of trabectedin in combination with venetoclax
Up to 6 months post-treatment
Secondary Outcomes (4)
Best response
Up to 6 months post-treatment
Progression free survival
From treatment initiation to disease progression or death, assessed up to 6 months post-treatment
Overall survival
From treatment initiation to death due to any cause, assessed up to 6 months post-treatment
Frequency of myeloid cells and of other immune cells
Baseline up to 6 months post-treatment
Study Arms (2)
Cohort I (BTK-refractory)
EXPERIMENTALPatients receive venetoclax PO QD beginning on day 1 for 5 weeks (cycle 1). Beginning in cycle 2, patients receive venetoclax PO QD and trabectedin IV over 3 hours on day 1. Cycles 2+ repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Cohort II (BTK-intolerant)
EXPERIMENTALPatients receive trabectedin IV over 3 hours on day 1 of a 3-week cycle (cycle 1), then receive venetoclax PO QD beginning on day 1 of a 5-week cycle (cycle 2). Beginning in cycle 3, patients receive trabectedin IV over 3 hours on day 1 and venetoclax PO QD every 3 weeks in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Given PO
Eligibility Criteria
You may qualify if:
- Patients with a diagnosis of CLL/SLL who are progressing (based on 2018 International Workshop on Chronic Lymphocytic Leukemia \[iwCLL\] criteria) on or intolerant to a BTK inhibitor (BTK-inhibitor-intolerant is defined as unable to maintain on a stable and continuous dose of at least ibrutinib 140 mg/day \[or acalabrutinib 100 mg/day\] for at least 2 weeks due to recurrent treatment-related grade 2 or higher non-hematologic toxicity by Common Terminology Criteria for Adverse Events \[CTCAE\] grading)
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
- Total bilirubin =\< 1.0 x upper limit of normal (ULN) or =\< 3 x ULN for patients with Gilbert's disease
- Creatinine clearance \> 50 mL/min (calculated according to institutional standards or using Cockcroft-Gault formula)
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST) =\< 2.5 x ULN
- Alkaline phosphatase (ALP) =\< 2.5 x ULN
- Platelet (PLT) count \>= 50,000/l, with no platelet transfusion in 2 weeks prior to registration, unless cytopenia is due to bone marrow involvement with CLL, in which case PLT count \> 30,000/l, with no PLT transfusion in 2 weeks prior to registration
- Absolute neutrophil count (ANC) \>= 1000/l, unless cytopenia is due to bone marrow involvement with CLL, in which case ANC \> 500/l
- Creatine phosphokinase (CPK) \< 2.5 x ULN
- Left ventricular ejection fraction (LVEF) assessed by multi-gated acquisition scan (MUGA) or echocardiogram within limits of normal range
- Women of childbearing potential must agree to use an effective contraception method during the study and for 60 days following the last dose of study drug. Women of non- childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy. Men who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 60 days following the last dose of study drug
- Free of prior malignancies for 2 years with exception of patients diagnosed with basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast, who are eligible even if they are currently treated or have been treated and/or diagnosed in the past 2 years prior to study enrollment. If patients have another malignancy that was treated within the last 2 years, such patients may be enrolled, if the likelihood of requiring systemic therapy for this other malignancy within 2 years is less than 20%
- Patients or their legally authorized representative must provide written informed consent
You may not qualify if:
- Radiotherapy or chemotherapy within 2 weeks prior to the first dose of the study drugs. Given the quick progression associated with resistance to BTK inhibitors, no limits will be placed to the use of BTK inhibitors for enrollment or initiation of treatment on this trial
- Uncontrolled active systemic infection (viral, bacterial, and fungal)
- Active, uncontrolled autoimmune phenomenon (autoimmune hemolytic anemia or immune thrombocytopenia) requiring steroid therapy with \> 20 mg daily of prednisone or equivalent
- Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 2 months of screening, or any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
- Patient is pregnant or breast-feeding
- Venetoclax-refractory CLL or prior treatment with trabectedin
- Malabsorption syndrome or other condition that precludes oral/enteral route of administration
- Patients who received the following within 7 days prior to first dose of venetoclax: moderate and strong CYP3A inhibitors and inducers, P-glycoprotein inhibitors, or narrow therapeutic index P-glycoprotein substrates AND patients who received the following within 3 days prior to first dose of venetoclax: grapefruit or grapefruit products, Seville oranges and star fruit
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
William G Wierda
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 19, 2019
First Posted
March 21, 2019
Study Start
June 18, 2019
Primary Completion
March 4, 2020
Study Completion
March 4, 2020
Last Updated
September 25, 2023
Record last verified: 2023-09