Trial Title:
Roginolisib (IOA-244) With Venetoclax and Rituximab for Refractory/Relapsed Chronic Lymphocytic Leukemia (CLL)
NCT ID:
NCT06644183
Condition:
Leukemia
Relapsed Leukemia
Chronic Lymphocytic Leukemia
Relapsed Cancer
Refractory Leukemia
Conditions: Official terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Rituximab
Venetoclax
Conditions: Keywords:
Leukemia
Relapsed Leukemia
Chronic Lymphocytic Leukemia
Relapsed Cancer
Refractory Leukemia
CLL
Relapsed Chronic Lymphocytic Leukemia
Refractory Chronic Lymphocytic Leukemia
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Sequential Assignment
Intervention model description:
Phase 1: single arm, Phase 2: two arm, randomized trial
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Roginolisib
Description:
Phosphoinositide 3-kinase delta inhibitor, 40 mg capsule, taken orally per protocol.
Arm group label:
Phase 1b Arm A: Venetoclax + Roginolisib + Rituximab Dose Level -1
Arm group label:
Phase 1b Arm B: Venetoclax + Roginolisib + Rituximab Dose Level 1
Arm group label:
Phase 2 Arm A: Venetoclax + Roginolisib + Rituximab
Other name:
MSC2360844A
Other name:
[6-fluoro-1-(4-morpholin-4-ylmethyl-phenyl)-5,5-dioxo-4,5-dihydro-1H-5λ6-thiochro-meno[4,3-c]pyrazol-3-yl]-morpholin-4-yl-methanone hemi-fumarate, C26 H27 F N4 O5 S. 0.5 C4H4O4
Intervention type:
Drug
Intervention name:
Venetoclax
Description:
B-cell lymphoma 2 inhibitor, 10, 50, and 100mg tablets, taken orally per standard of
care.
Arm group label:
Phase 1b Arm A: Venetoclax + Roginolisib + Rituximab Dose Level -1
Arm group label:
Phase 1b Arm B: Venetoclax + Roginolisib + Rituximab Dose Level 1
Arm group label:
Phase 2 Arm A: Venetoclax + Roginolisib + Rituximab
Arm group label:
Phase 2 Arm B: Venetoclax + Rituximab
Other name:
ABT-199
Other name:
GDC-0199
Intervention type:
Drug
Intervention name:
Rituximab
Description:
Chimeric anti-CD 20 monoclonal antibody, single-use 10 and 50mL vials, via intravenous
(into the vein) infusion per standard of care.
Arm group label:
Phase 1b Arm A: Venetoclax + Roginolisib + Rituximab Dose Level -1
Arm group label:
Phase 1b Arm B: Venetoclax + Roginolisib + Rituximab Dose Level 1
Arm group label:
Phase 2 Arm A: Venetoclax + Roginolisib + Rituximab
Arm group label:
Phase 2 Arm B: Venetoclax + Rituximab
Other name:
Riabni
Other name:
Ruxience
Other name:
Truxima
Other name:
Rituxan
Other name:
ABP 798
Other name:
IDEC-C2B8, PF-05280586
Other name:
MabThera
Summary:
This research study will test the safety and anticancer activity of the combination of
three drugs (Roginolisib, Venetoclax, and Rituximab) for participants with relapsed or
refractory Chronic Lymphocytic Leukemia (CLL).
The names of the study drugs involved in this study are:
- Roginolisib (a novel type of PI3-kinase delta inhibitor)
- Venetoclax (a type of B-cell lymphoma 2 inhibitor)
- Rituximab (a type of monoclonal antibody)
Detailed description:
This is a Phase I/II, open-label, randomized, and comparator controlled study to test the
safety and anticancer activity of the combination of three drugs (Roginolisib,
Venetoclax, and Rituximab) for participants with relapsed or refractory Chronic
Lymphocytic Leukemia (CLL). In this study, investigators are assessing whether adding the
study drug, Roginolisib, will lead to deeper responses than the standard combination of
Venetoclax and Rituximab alone.
A phase Ib safety lead-in portion of the trial will determine the dose and tolerability
of Roginolisib with the standard 2-drug combination treatment of Venetoclax + Rituximab.
In the phase 2 portion of the trial, participants will be randomized into one of two
treatment arms: Arm A: Roginolisib + Venetoclax and Rituximab vs. Arm B: Venetoclax and
Rituximab. Randomization means a participant is placed into a treatment arm by chance.
The U.S. Food and Drug Administration (FDA) has not approved Roginolisib as a treatment
for relapsed or refractory CLL.
The U.S. FDA has approved Venetoclax and Rituximab as a standard 2-drug combination
treatment for relapsed or refractory CLL.
The research study procedures include screening for eligibility in-clinic visits, blood
tests, urine tests, electrocardiograms (ECGs), Computerized Tomography (CT) scans,
Magnetic Resonance Imaging (MRI) scans, and bone marrow biopsy and/or aspirations.
Participants will receive study treatment for approximately 12 months and will be
followed for up to 5 years.
It is expected about 3-12 people will take part in the Phase 1 portion of the trial, and
52 people will participate in the Phase 2 portion of the research study.
iOnctura SA is supporting this research study by providing the study drug, Roginolisib.
The U.S. Department of Defense (DOD) is supporting this research study by providing
funding.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients with relapsed/refractory CLL who meet iwCLL criteria for requiring
treatment.
- Patients with measurable disease as defined by at least one of: circulating
lymphocytosis > 5000 B cells/microliter, bone marrow involvement > 30%, palpable
splenomegaly or lymph nodes > 1.5 cm. Computer tomography (CT) at screening must be
performed and followed every 2 cycles (1 cycle = 28 days).
- Patients must have received at least two prior therapies for CLL including systemic
therapy containing a covalent BTK inhibitor.
- Patients willing to undergo a pre-treatment and on treatment bone marrow biopsy.
- Age ≥18 years, at the time of signing the IRB approved informed consent. Because no
dosing or adverse event data are currently available on the use of venetoclax in
combination with roginolisib in participants <18 years of age, children are excluded
from this study, but will be eligible for future pediatric trials.
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
- Participants must meet the following organ and marrow function as defined below:
- Platelet count ≥50 x 109/L^^^
- Total bilirubin ≤ 1.5 ×institutional upper limit of normal (ULN)*
- AST(SGOT)/ALT(SGPT) ≤3.0 × institutional ULN
- Creatinine clearance ≥ 60 mL/min**
- ^^^Thrombocytopenia due to marrow involvement of CLL: > 30 x 109/L for the
safety run-in, and 20 x 109/L for the randomized portion of the study
- *unless increase attributed to leukemic organ involvement, hemolysis or
Gilbert's syndrome. Patients who are < 75 years may have bilirubin of ≤ 3.0 ×
ULN
- ** calculated by the Cockcroft Gault formula or measured by 24 hours urine
collection
- Patients with clinically inactive CNS disease or treated CNS disease that is no
longer symptomatic, or who need corticosteroids or anticonvulsants may be enrolled
in the study. For patients who have symptoms present, imaging and lumbar puncture
must be performed to exclude a CNS condition that may impact the study conduct.
- Willingness to undergo a pre-treatment and on-treatment bone marrow to evaluate MRD.
- Willingness to use adequate contraception prior to study entry and for the duration
of study participation.
- The effects of roginolisib on the developing human fetus are unknown.
- Venetoclax may cause embryo fetal harm when administered to pregnant women.
Anti-CD20 targeting agents are likely to cause fetal B-cell depletion. For this
reason women of child-bearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior
to study entry and for the duration of study participation. Women of
child-bearing potential will be required to have a negative serum pregnancy
test during screening and a negative serum pregnancy test on Cycle 1 Day 1.
Should a woman become pregnant or suspect she is pregnant while she or her
partner is participating in this study, she should inform her treating
physician immediately.
- Men treated or enrolled on this protocol must also agree to use adequate
contraception prior to the study, for the duration of study participation, and
4 months after completion of roginolisib or venetoclax administration.
Contraception must be conducted up to 12 months after taking the last rituximab
dose.
- Ability to understand and the willingness to sign a written informed consent
document, which includes compliance with the requirements of this protocol.
- Eligible to receive infection prophylaxis and supportive care as per institutional
guidelines.
Exclusion Criteria:
- Patients who have received prior treatment with venetoclax or PI3K inhibitors in the
last 6 months. Patients must not have had any CLL-directed anticancer therapy within
5 half- lives of the therapy prior to Cycle 1 Day 1.
- Patients who have received a live vaccine within 30 days of planned start of study
therapy. With regards to other type of vaccines, including SARS-Co2 vaccines, these
are allowed.
- Patients requiring ongoing treatment with chronic high dose immunosuppressants
(e.g., cyclosporine) or systemic steroids > 20 mg prednisone (or equivalent) QD. For
example, patients with uncontrolled autoimmune haemolytic anaemia (AIHA) or
idiopathic thrombocytopenia purpura (ITP), which requires > 20 mg once daily (QD) of
prednisone (or equivalent) to maintain haemoglobin levels of >8.0 g/dL or platelets
> 10,000 mL without transfusion support.
- History of transformation of CLL to aggressive non-Hodgkin lymphoma (Richter´s
transformation or pro-lymphocytic leukaemia) which may otherwise interfere with the
interpretation of the outcome of the study (including biomarker evaluation).
- Patients who have not recovered from adverse events due to prior anti-cancer therapy
(i.e., have residual toxicities > Grade 1) with the exception of alopecia or
fatigue. Any irAEs from prior immunotherapy must have complete resolution and must
have resolved at least 2 weeks before Cycle1 Day1.
- Participants who are receiving any other investigational agents for this condition.
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition to roginolisib or venetoclax or their formulation components or
prior anti- CD20 targeting agents more than 6 months before initiating study
treatments.
- Patients with a history of systemic autoimmune disease.
- Participants receiving any medications or substances that are strong inhibitors or
inducers of CYP3A are ineligible. Moderate CYP3A inhibitors and P-gp inhibitors can
be administered when venetoclax dose is reduced to 50%. Otherwise, venetoclax is
contraindicated in patients requiring strong or moderate CYP3A inducers.
- Because of ongoing research, regularly consulting medical reference databases
is recommended. One such reference is the Website of the US-FDA: (Drug
Interactions | Relevant Regulatory Guidance and Policy Documents | FDA)
- As part of the enrollment/informed consent procedures, the participant will be
counseled on the risk of interactions with other agents, and what to do if new
medications need to be prescribed or if the participant is considering a new
over-the-counter medicine or herbal product.
- Pregnant women are excluded from this study because venetoclax has the potential to
cause embryo-fetal harm, and the potential for teratogenic or abortifacient effects
with roginolisib is currently unknown. Because there is an unknown but potential
risk for adverse events in nursing infants secondary to treatment of the mother with
roginolisib or venetoclax breastfeeding should be discontinued if the mother is
treated with these agents.
- Patients with a history of other primary malignancy are excluded when they require
therapy that will interfere with the investigational treatments. Exceptions are if
the natural history or treatment does not have the potential to interfere with the
safety or efficacy assessment of the investigational regimen. For example:
- Malignancies surgically treated with curative intent and with no known active
disease present for ≥2 years before the first dose of study treatment.
- Adequately treated nonmelanoma skin cancer or lentigo maligna without evidence
of disease.
- Adequately treated cervical carcinoma in situ without evidence of disease.
- Surgically/adequately treated low-grade, early-stage, localized prostate cancer
without evidence of disease or low risk localized prostate cancer on
observation.
- Inability to swallow food or any condition of the upper gastrointestinal tract that
precludes administration of oral medications.
- History or presence of cardiovascular disease, which in the Investigator's opinion
may impact the clinical trial participation. Patients with a QTcF > 470 msec at
screening.
- History of tuberculosis treatment within the preceding two years.
- Ongoing systemic bacterial, fungal, or viral infections (including also hepatitis
viral infection) at the time of initiation of study treatment (defined as requiring
intravenous [IV] antimicrobial, antifungal or antiviral agents). Subjects on
antimicrobial, antifungal or antiviral prophylaxis are not specifically excluded if
all other inclusion/exclusion criteria are met, there is no evidence of active
infection at enrollment, and ongoing treatment does not have a significant risk of
drug-drug interaction with venetoclax.
- Known Human immunodeficiency virus (HIV) infection which is treated with agents that
can interfere with venetoclax due to potential drug-drug interactions or increased
risk of myelotoxicity.
- Any serious or uncontrolled medical disorder or active infection that, in the
opinion of the Investigator, may increase the risk associated with study
participation, study drug administration, or would impair the ability of the patient
to receive protocol therapy.
- Known alcohol or substance abuse.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02115
Country:
United States
Contact:
Last name:
Jennifer Brown, MD, PhD
Phone:
617-632-5847
Email:
Jennifer_brown@dfci.harvard.edu
Investigator:
Last name:
Jennifer Brown, MD, PhD
Email:
Principal Investigator
Start date:
April 2025
Completion date:
October 1, 2032
Lead sponsor:
Agency:
Jennifer R. Brown, MD, PhD
Agency class:
Other
Collaborator:
Agency:
United States Department of Defense
Agency class:
U.S. Fed
Source:
Dana-Farber Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06644183
