Chronic Lymphocytic Leukemia
Conditions
Keywords
umbralisib, ublituximab, venetoclax, ibrutinib, CLL, acalabrutinib
Brief summary
Phase 2, two cohort trial evaluating the addition of ublituximab and umbralisib on the rate of minimal residual disease (MRD) negativity in participants with Chronic Lymphocytic Leukemia (CLL), who are currently on treatment with ibrutinib, alacabrutinib or venetoclax.
Detailed description
This is a Phase 2 open label, two treatment cohort trial evaluating the addition of ublituximab and umbralisib on the rate of minimal residual disease (MRD) negativity in participants with CLL, who fail to achieve MRD negativity, after a minimum 6-month treatment with ibrutinib, alacabrutinib or venetoclax.
Interventions
DRUGUblituximab
* recombinant chimeric anti-CD20 monoclonal antibody * administered as an IV infusion
DRUGUmbralisib
* Phosphoinositide-3-kinase (PI3K) delta inhibitor * Tablet form, to taken orally on a daily basis
DRUGIbrutinib
* Bruton Tyrosine Kinase (BTK) inhibitor * Tablet form, to taken orally on a daily basis
DRUGVenetoclax
* BCL-2 inhibitor * Tablet form, to be taken orally
DRUGAcalabrutinib Oral Capsule
Kinase inhibitor, capsule form, to be taken orally
Sponsors
TG Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants with Chronic Lymphocytic Leukemia (CLL) who have been on treatment for at least 6 months * Minimal Residual Disease positive at screening * Adequate organ system function as specified in the protocol * Ability to follow protocol procedures.
Exclusion criteria
* Participants receiving cancer therapy or any investigational drug within 21 days of Cycle 1, Day 1. * Participants with a known histological transformation * Active Hepatitis B or Hepatitis C.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Undetected Minimal Residual Disease (U-MRD) | Up to approximately 23 months | U-MRD rate was defined as the proportion of participants who have undetectable MRD in the peripheral blood as confirmed by central lab. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Up to approximately 34 months | ORR was defined as percent of participants who achieve complete response (CR) or partial response (PR). CR was defined as no evidence of new disease, regression of all target nodal masses to normal size \< or = 1.5 cm in the longest diameter (LD) and an absolute lymphocyte count (ALC) in peripheral blood \< 4\*10\^9/L. PR was defined as no evidence of new disease, a decrease in peripheral blood ALC by ≥50% from baseline or a decrease to \<4 x 10\^9/L or a decrease by ≥50% from the baseline in the sum of the products (SPD) of the target nodal lesions or a decrease by ≥50% from baseline in the CLL marrow infiltrate or in B lymphoid, no target, splenic, liver, or non-target disease with worsening that meets the criteria for definitive nodules, peripheral blood counts with ANC \>1.5 x 10\^9/L or platelet count ≥100 x 10\^9/L or hemoglobin ≥110 g/L (11.0 g/dL) without red blood cell transfusions, all without need for exogenous growth factors. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) as Assessed by National Cancer Institute - Common Terminology Criteria for Adverse Events-Version (NCI-CTCAE-V5) | Up to approximately 34 months | An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product. An AE does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. A TEAE is an AE that starts or worsens after receiving study drug. |
Countries
United States
Participant flow
Recruitment details
A total of 41 participants were enrolled at 8 investigative sites across United States.
Participants by arm
| Arm | Count |
|---|---|
| Ublituximab + Umbralisib + Ibrutinib Participants were administered with ublituximab, 900 milligrams (mg), intravenous (IV) infusion once every cycle through cycle 6, then every three cycles upto 24 cycles; umbralisib, 800 mg, oral tablet, daily through Cycles 1-24; ibrutinib oral tablet daily (1 Cycle = 28 days). | 30 |
| Ublituximab + Umbralisib + Venetoclax Participants were administered with ublituximab, 900 milligrams (mg), intravenous (IV) infusion once every cycle through cycle 6, then every three cycles upto 24 cycles; umbralisib, 800 mg, oral tablet, daily through Cycles 1-24; venetoclax oral tablet daily (1 Cycle = 28 days). | 6 |
| Ublituximab + Umbralisib + Acalabrutinib Participants were administered with ublituximab, 900 milligrams (mg), intravenous (IV) infusion once every cycle through cycle 6, then every three cycles upto 24 cycles; umbralisib, 800 mg, oral tablet, daily through Cycles 1-24; acalabrutinib oral capsule every 12 hours (1 Cycle = 28 days). | 5 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Sponsor's Discretion | 30 | 6 | 5 |
Baseline characteristics
| Characteristic | Ublituximab + Umbralisib + Ibrutinib | Ublituximab + Umbralisib + Venetoclax | Ublituximab + Umbralisib + Acalabrutinib | Total |
|---|---|---|---|---|
| Age, Continuous | 63 years | 54.5 years | 71 years | 63 years |
| Race and Ethnicity Not Collected | — | — | — | 0 Participants |
| Sex: Female, Male Female | 7 Participants | 1 Participants | 0 Participants | 8 Participants |
| Sex: Female, Male Male | 23 Participants | 5 Participants | 5 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Rate of Undetected Minimal Residual Disease (U-MRD)
U-MRD rate was defined as the proportion of participants who have undetectable MRD in the peripheral blood as confirmed by central lab.
Time frame: Up to approximately 23 months
Population: Data for this outcome measure was not collected or analyzed as planned as the study was terminated due to sponsor's business decision.
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) as Assessed by National Cancer Institute - Common Terminology Criteria for Adverse Events-Version (NCI-CTCAE-V5)
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product. An AE does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. A TEAE is an AE that starts or worsens after receiving study drug.
Time frame: Up to approximately 34 months
Population: Data for this outcome measure was not collected or analyzed as planned as the study was terminated due to sponsor's business decision.
Secondary
Overall Response Rate (ORR)
ORR was defined as percent of participants who achieve complete response (CR) or partial response (PR). CR was defined as no evidence of new disease, regression of all target nodal masses to normal size \< or = 1.5 cm in the longest diameter (LD) and an absolute lymphocyte count (ALC) in peripheral blood \< 4\*10\^9/L. PR was defined as no evidence of new disease, a decrease in peripheral blood ALC by ≥50% from baseline or a decrease to \<4 x 10\^9/L or a decrease by ≥50% from the baseline in the sum of the products (SPD) of the target nodal lesions or a decrease by ≥50% from baseline in the CLL marrow infiltrate or in B lymphoid, no target, splenic, liver, or non-target disease with worsening that meets the criteria for definitive nodules, peripheral blood counts with ANC \>1.5 x 10\^9/L or platelet count ≥100 x 10\^9/L or hemoglobin ≥110 g/L (11.0 g/dL) without red blood cell transfusions, all without need for exogenous growth factors.
Time frame: Up to approximately 34 months
Population: Data for this outcome measure was not collected or analyzed as planned as the study was terminated due to sponsor's business decision.