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Chronic Lymphocytic LeukemiaPhase 2NCT04149821

Umbralisib Plus Ublituximab (U2) in Progressive CLL After Novel Therapy

A Phase 2 study testing Umbralisib and Ublituximab in people with Chronic Lymphocytic Leukemia and CLL Progression, run by Weill Medical College of Cornell University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study evaluates the efficacy and safety of umbralisib and ublituximab (U2) as salvage therapy in patients with chronic lymphocytic leukemia (CLL) who have progressed either on a BTK inhibitor (BTKi) or BCL-2 inhibitor. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Umbralisib and Ublituximab
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteUnited States
Study dates
10 Feb 2021to 9 Jun 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • confirmed diagnosis of CLL based upon 2018 International Workshop on CLL (IWCLL) criteria.
  • Patient must have progressed on a BTK or BCL-2 containing regimen as the prior line of therapy. Patients who were treated with a regimen containing both classes of novel agents will be allowed to enroll and will be enrolled into Cohort B. Patients who receive a temporizing non-experimental treatment such as an anti-CD20 monoclonal antibody, corticosteroid including high dose methylprednisolone after progression on a BTK or BCL-2 inhibitor will be considered for enrollment after discussion with the study sponsor.
  • Age ≥18 years
  • ECOG performance status ≤2
  • Patient must have adequate bone marrow function and meet the below thresholds:
  • Absolute neutrophil count of ≥ 750 cell/μL in absence of G-CSF for 7 days prior to enrollment.
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  • Platelet count of ≥ 30,000 cells/μL, or ≥ 20,000 cells/μL if there is bone marrow involvement)
  • Patient must have adequate organ function and meet the thresholds below:
  • Total bilirubin ≤ 1.5 times the upper limit of normal (ULN). Subjects with bilirubin exceeding this limit due to Gilbert's disease are eligible
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x ULN if no liver involvement or ≤5 x the ULN if known liver involvement
  • Creatinine clearance >30 ml/min/1.73m2 as calculated by the MDRD equation
  • Ability to swallow and retain oral medication.
  • Females who are not of child-bearing potential, and females of child-bearing potential (FCBP) who have a negative serum pregnancy test within 3 days prior to initial trial treatment. Males of reproductive potential may not participate unless they agree to use medically acceptable contraception. FCBP and all male partners, and male subjects must consent to use a medically acceptable method of contraception throughout the study period and for 4 months after the last dose of study drug
  • Willingness and ability to comply with trial and follow-up procedures, and give written informed consent

Who cannot join

  • Patient has had prior exposure to a PI3K inhibitor at any point in treatment history
  • Patient has discontinued the BTK or BCL2 inhibitor due to intolerance. Intolerance will be defined as discontinuing prior BTKi or BCL-2 therapy for any reason without evidence of progression. Patients who were re-challenged after discontinuation for therapeutic reasons will be allowed if the toxicity did not recur or was managed without indication for discontinuation. Patients who progress on BTKi or BCL-2 therapy who were on a reduced dose due to an AE/intolerance are eligible as long as progression has been documented on that reduced dose.
  • Patient has clinical or radiographic evidence of, or has biopsy proven Richter's transformation or prolymphocytic leukemia.
  • Patient has undergone an allogeneic stem cell transplant.
  • Patient has received an autologous hematologic stem cell transplant within 6 months of study entry.
  • Prior history of malignancy within 3 years of study enrollment except for adequately treated basal, squamous cell carcinoma or non-melanomatous skin cancer, carcinoma in situ of the cervix, superficial bladder cancer not treated with intravesical chemotherapy or BCG within 6 months, localized prostate cancer and PSA <1.0 mg/dL on 2 consecutive measurements at least 3 months apart with the most recent one being within 4 weeks of study entry.
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  • Patient is known to be positive for HIV.
  • Patient has history of hepatitis C infection, active infection with hepatitis B or active cytomegalovirus (CMV) as determined by PCR.
  • Patient has previous exposure to a BTK inhibitor therapy within 14 days of initiating study treatment on Cycle 1 Day 1, or previous exposure to anti-cancer therapy including chemotherapy, radiotherapy, or investigational therapy, including other targeted small molecule agents within 21 days of initiating study treatment on Cycle 1 Day 1.
  • Evidence of ongoing systemic bacterial, fungal or viral infection, except localized fungal infections of skin or nails.
  • History of anaphylaxis (excluding infusion related reactions) in association with previous anti-CD20 administration.
  • Inflammatory bowel disease (such as Crohn's disease or ulcerative colitis).
  • Malabsorption syndromes.
  • Irritable bowel syndrome with greater than 3 loose stools per day as a baseline.
  • Any severe and/or uncontrolled medical conditions or other conditions that could affect participation in the study such as:
  • Symptomatic, or history of documented congestive heart failure (New York Heart Association functional classification III-IV)[see Appendix: NYHA Classifications]
  • Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, CHF, or myocardial infarction within 6 months of enrollment.
  • Concomitant use of medication known to cause QT prolongation or torsades de pointes should be used with caution and at investigator discretion.
  • Poorly controlled or clinically significant atherosclerotic vascular disease including cerebrovascular accident (CVA), transient ischemic attack (TIA), angioplasty, cardiac or vascular stenting within 6 months of enrollment.
  • Females who are pregnant or lactating.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Weill Cornell Medicine

    New York, New York, 10065

Other trials in United States

About this study

Official title: Phase II Study of Umbralisib Plus Ublituximab (U2) in Progressive CLL After Novel Therapy

This study evaluates the efficacy and safety of umbralisib and ublituximab (U2) as salvage therapy in patients with chronic lymphocytic leukemia (CLL) who have progressed either on a BTK inhibitor (BTKi) or BCL-2 inhibitor. The study will evaluate this combination in two parallel cohorts and subjects will be assigned based on which class of novel agent-containing regimen was used prior. Cohort A will consist of patients who progress after BTKi containing regimens and Cohort B will consist of patients who progress after a BCL-2 containing regimen. Subjects who progress on a regimen containing both a BTKi and a BCL-2 inhibitor, will be enrolled in cohort B. Each cohort will be evaluated independently of each other.

Read the detailed description

This is a single-center, two cohort Phase 2 clinical trial investigating the effectiveness of umbralisib and ublituximab in patients with progressive CLL. Cohort A will consist of patients who who have progressed after receiving either a BTK inhibitor (BTKi) or BCL-2 inhibitor.

Being tested
Umbralisib, Ublituximab
Keywords
CLL, progression
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Disease Progression

What participants receive

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

  • UmbralisibDrug

    Also called TGR-1202

    • Lead-in cycle of 28 days (Cycle -1) of umbralisib monotherapy, 800mg oral daily
    • Continued 800mg oral daily dosing in all subsequent cycles (combination therapy cycles 1-6, then continued monotherapy cycle 7 and beyond)

  • UblituximabDrug

    Also called TG-1101

    -Co-administered on days 1 and 2 (dose split over days 1 and 2), 8, 15 of cycle 1 then on day 1 for subsequent cycles 2-6

Study groups in NCT04149821
Study groupRoleWhat they receive
Cohort A Post BTKi TherapyExperimentalPatients who progress after a BTKi containing regimen
Receives: Drug: Umbralisib; Drug: Ublituximab
Cohort B Post BCL-2 TherapyExperimental* Patients who progress after BCL-2 containing regimens * Patients who progress on a regimen containing both a BTKi and a BCL-2 inhibitor
Receives: Drug: Umbralisib; Drug: Ublituximab

What is being measured

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

  1. Efficacy of Umbralisib in Combination With Ublituximab (U2) as Measured by Overall Response Rate (ORR) in Patients With CLL Who Have Progressed on a BTKi or BCL-2 Inhibitor

    Number of subjects who achieve a partial or complete response

    Measured: 11 months

Secondary outcomes (3)

  1. Safety of Umbralisib in Combination With Ublituximab (U2) as Measured by the Percentage of Subjects Who Experience 1 or More Adverse Events

    Rate of subjects who experience 1 or more adverse events

    Measured: 1 year and 4 months

  2. Complete Remission Rate as Measured by the Number of Subjects Who Achieve Complete Response as Their Best Response

    Number of subjects who achieve complete response on study

    Measured: 1 year and 4 months

  3. Duration of Response

    Median interval of time between subjects' first objective response to the first sign of disease progression

    Measured: 1 year and 4 months

Timeline

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

  1. First posted4 Nov 2019
  2. Study start10 Feb 2021
  3. Primary completion21 Jan 2022
  4. Study completion9 Jun 2022

Why it stopped: Terminated due to low accrual

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04149821
Sponsor's protocol ID
19-06020316
Status last verified
May 2023
First submitted
30 Oct 2019
Last updated
15 Jun 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Umbralisib and Ublituximab in people with Chronic Lymphocytic Leukemia and CLL Progression, run by Weill Medical College of Cornell University 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 14 inclusion and 20 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: stopped early, as of the sponsor's last update on 15 Jun 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Efficacy of Umbralisib in Combination With Ublituximab (U2) as Measured by Overall Response Rate (ORR) in Patients With CLL Who Have Progressed on a BTKi or BCL-2 Inhibitor (time frame: 11 months). 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 NCT04149821.

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 15 Jun 2023.

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