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Refractory Chronic Lymphocytic LeukemiaPhase 1NCT03884972

Trabectedin and Venetoclax in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Resistant or Intolerant to a BTK Inhibitor

A Phase 1 study testing Trabectedin and Venetoclax in people with Refractory Chronic Lymphocytic Leukemia and Refractory Small Lymphocytic Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Trabectedin and Venetoclax
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
18 Jun 2019to 4 Mar 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 13Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: 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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate safety and tolerability, and to determine dose and schedule of trabectedin in combination with venetoclax in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) resistant or intolerant to a BTK inhibitor.

SECONDARY OBJECTIVES:

  1. To determine the best response achieved by patients treated with combined trabectedin and venetoclax.

II. To determine the progression-free (PFS) and overall survival (OS) of patients treated with combined trabectedin and venetoclax.

III. To investigate the effects of trabectedin on CLL cells and on the components of the CLL microenvironment.

IV. To investigate associations between baseline characteristics (including fluorescence in situ hybridization [FISH] status, IGHV mutation status and mutations responsible for resistance to BTK inhibitors) and response to the combination of trabectedin and venetoclax.

OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 2 cohorts.

COHORT I (BTK-REFRACTORY): Patients receive venetoclax orally (PO) once daily (QD) beginning on day 1 for 5 weeks (cycle 1). Beginning in cycle 2, patients receive venetoclax PO QD and trabectedin intravenously (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): Patients 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.

After completion of study treatment, patients are followed up every 6 months.

Being tested
Trabectedin, Venetoclax
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TrabectedinDrug

    Also called Ecteinascidin, ecteinascidin 743, ET-743, Yondelis

    Given IV

  • VenetoclaxDrug

    Also called ABT-0199, ABT-199, ABT199, GDC-0199

    Given PO

Study groups in NCT03884972
Study groupRoleWhat they receive
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.
Receives: Drug: Trabectedin; Drug: Venetoclax
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.
Receives: Drug: Trabectedin; Drug: Venetoclax

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose and schedule of trabectedin in combination with venetoclax

    Measured: Up to 6 months post-treatment

Secondary outcomes (4)

  1. Best response

    Will be assessed using the 2018 International Workshop on Chronic Lymphocytic Leukemia response criteria. Minimal residual disease will be evaluated by 4-color flow cytometry.

    Measured: Up to 6 months post-treatment

  2. Progression free survival

    Measured: From treatment initiation to disease progression or death, assessed up to 6 months post-treatment

  3. Overall survival

    Measured: From treatment initiation to death due to any cause, assessed up to 6 months post-treatment

  4. Frequency of myeloid cells and of other immune cells

    Will be analyzed in the peripheral blood and bone marrow (if available).

    Measured: Baseline up to 6 months post-treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Mar 2019
  2. Study start18 Jun 2019
  3. Primary completion4 Mar 2020
  4. Study completion4 Mar 2020 (estimated)

Why it stopped: Request by sponsor due to no enrollment of participants on study

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03884972
Sponsor's protocol ID
2018-0302
Other IDs
NCI-2019-01555, 2018-0302, P30CA016672
Status last verified
Sep 2023
First submitted
19 Mar 2019
Last updated
25 Sep 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Trabectedin and Venetoclax in people with Refractory Chronic Lymphocytic Leukemia and Refractory Small Lymphocytic Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 25 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose and schedule of trabectedin in combination with venetoclax (time frame: Up to 6 months post-treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03884972.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2023.

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