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Roginolisib (IOA-244) With Venetoclax and Rituximab for Refractory/Relapsed Chronic Lymphocytic Leukemia (CLL)

ConditionsLeukemiaRelapsed LeukemiaChronic Lymphocytic LeukemiaRelapsed CancerRefractory Leukemia
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorJennifer R. Brown, MD, PhD

About this trial

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)

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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).

Trial design

Design model

Sequential

Treatments tested in this trial

  • Roginolisib

    Drug

    Phosphoinositide 3-kinase delta inhibitor, 40 mg capsule, taken orally per protocol.

  • Venetoclax

    Drug

    B-cell lymphoma 2 inhibitor, 10, 50, and 100mg tablets, taken orally per standard of care.

  • Rituximab

    Drug

    Chimeric anti-CD 20 monoclonal antibody, single-use 10 and 50mL vials, via intravenous (into the vein) infusion per standard of care.

Treatment groups

64 Participants
are divided into 4 treatment groups
Group A: Phase 1b Arm A: Venetoclax + Roginolisib + Rituximab Dose Level -1Experimental treatment 3 interventions
Group B: Phase 1b Arm B: Venetoclax + Roginolisib + Rituximab Dose Level 1Experimental treatment 3 interventions
Group C: Phase 2 Arm A: Venetoclax + Roginolisib + RituximabExperimental treatment 3 interventions
Group D: Phase 2 Arm B: Venetoclax + RituximabActive comparator 2 interventions

Trial outcomes

Primary outcomes

1

Undetectable Minimal Residual Disease(uMRD) rate by ClonoSEQ assay

uMRD rate is defined as the proportion of participants with uMRD after treatment with either roginolisib plus venetoclax + rituximab, or venetoclax+ rituximab, as measured in bone marrow at a level of 10-4 by the clonoSEQ assay.

Time frame
1 year

Secondary outcomes

1

Adverse Event of Interest Rate

Adverse event of interest rate is defined as the percentage of participants who experienced an adverse event including transaminitis, rash, diarrhea, colitis and pneumonitis as well as febrile neutropenia and infection. Assessment will be based on NCI CTCAE grading for non-hematologic toxicity, and iwCLL criteria for hematologic toxicity.

Time frame
1 year
2

Undetectable Minimal Residual Disease(uMRD) rate by flow cytometry

uMRD as measured in blood at same timepoint as ClonoSeq.

Time frame
5 years
3

Median Progression Free Survival(PFS)

PFS based on Kaplan Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Participants alive without PD were censored at the earliest of the date of the last disease evaluation.

Time frame
5 years
4

Median Overall Survival (OS)

Overall survival based on the Kaplan-Meier method is defined as the time from randomization to death. Participants alive are censored at the last date of contact (including lost-to-follow-up) or at the date of withdrawal of consent, if relevant.

Time frame
5 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Jennifer R. Brown, MD, PhD

Lead sponsor

Dana-Farber Cancer Institute

Sponsor institution

United States Department of Defense

Collaborator

Source ClinicalTrials.gov
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