Pirtobrutinib and Venetoclax With MRD Detection for Previously Untreated Chronic Lymphocytic Leukemia
MC210806 Phase 2 Study of MRD Guided, FIxed DuRation TherApy for Previously Untreated Chronic Lymphocytic LeukEmia With Pirtobrutinib and Venetoclax (MIRACLE)
3 other identifiers
interventional
72
1 country
1
Brief Summary
This phase II trial studies how well pirtobrutinib and venetoclax work in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. This study also seeks to adopt a blood test which shows a small number of cancer cells in the body after cancer treatment called minimal residual disease as a guide to determine length of treatment. Drugs used in chemotherapy, such as pirtobrutinib and venetoclax, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Identifying minimal residual disease results after combination chemotherapy may help guide future treatment decisions for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jan 2023
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 28, 2022
CompletedFirst Posted
Study publicly available on registry
January 10, 2023
CompletedStudy Start
First participant enrolled
January 31, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 11, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 3, 2030
February 12, 2026
February 1, 2026
3.8 years
December 28, 2022
February 10, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Undetected minimal residual disease (uMRD)
Success of uMRD (\< 1/10\^4) will be measured by ClonoSEQ in both peripheral blood and bone marrow. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true rate of uMRD by ClonoSEQ in both peripheral blood and bone marrow after cycle 15 will be calculated.
After cycle 15 (1 cycle = 28 days)
Secondary Outcomes (9)
Peripheral blood uMRD rate
Up to 3 years
Bone marrow uMRD rate
Up to 3 years
Overall response rate
Up to 3 years
Complete response rate
Up to 3 years
Duration of response
From when patient's objective status is first noted to be either a CR, CRi, PR, or nPR to the earliest date on which progressive disease is documented by the iwCLL criteria, assessed up to 3 years
- +4 more secondary outcomes
Study Arms (1)
Treatment (pirtobrutinib and venetoclax)
EXPERIMENTALPatients receive pirtobrutinib and venetoclax PO on study. Patients also undergo CT, MRI, and PET scans during screening and on study. Patients also undergo bone marrow aspiration and bone marrow biopsy, and collection of blood, tissue, stool, and saliva samples on study.
Interventions
Undergo MRI scan
Undergo PET scan
Given PO
Undergo ECHO
Undergo MUGA
Given PO
Undergo collection of blood, tissue, stool, and saliva samples
Undergo bone marrow aspiration
Undergo bone marrow biopsy
Undergo CT scan
Eligibility Criteria
You may qualify if:
- Age \>= 18 years.
- Confirmed diagnosis of CLL according to the International Workshop on (iw)CLL 2018 criteria or biopsy proven small lymphocytic lymphoma (SLL) according to the World Health Organization (WHO) criteria.
- NOTE: The diagnosis of CLL requires the presence of \> 5 × 10\^9/L B lymphocytes in the peripheral blood. Typically, CLL cells express CD19, CD5, and CD23, with variable expression of CD20 (typically dim), and show kappa or lambda light chain restriction.
- NOTE: A diagnosis of mantle cell lymphoma must be excluded by demonstrating a negative cyclin D1 expression and/or a negative t(11;14) translocation.
- No prior CLL/SLL-directed therapy such as chemotherapy, immunotherapy, targeted therapy with small molecule inhibitors, radiation therapy, or cellular therapy.
- NOTE: Nutraceutical treatments with no established benefit in CLL (such as epigallocatechin gallate or EGCG, found in green tea or other herbal treatments or supplemental vitamins) will not be considered prior CLL/SLL-directed therapy.
- NOTE: Prior corticosteroid therapy for an indication other than CLL/SLL will not be considered prior CLL/SLL-directed therapy.
- NOTE: A short course of corticosteroid (e.g., =\< 1 week of intravenous or =\< 2 weeks of oral corticosteroid) given for acute SLL-related symptoms or impending severe organ dysfunction is allowed.
- Provide written informed consent.
- Patients with SLL must have a measurable B-cell clone (of CLL immunophenotype) in either peripheral blood or bone marrow (e.g., by flow cytometry) at baseline.
- Meeting at least one of the following indications for treatment:
- Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (Hb \< 11 g/dL) and/or thrombocytopenia (platelet counts \< 100 × 10\^9/L).
- Massive (i.e., \>= 6 cm below the left costal margin) or progressive or symptomatic splenomegaly.
- Massive nodes (i.e., \>= 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy.
- Progressive lymphocytosis with an increase of \>= 50% over a 2-month period, or lymphocyte doubling time (LDT) \< 6 months. LDT can be obtained by linear regression extrapolation of absolute lymphocyte counts obtained at intervals of 2 weeks over an observation period of 2 to 3 months; patients with initial blood lymphocyte counts \< 30 × 10\^9/L may require a longer observation period to determine the LDT. Factors contributing to lymphocytosis other than CLL (e.g., infections, steroid administration) should be excluded.
- +21 more criteria
You may not qualify if:
- Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
- Pregnant persons.
- Nursing persons (lactating persons are eligible provided that they agree not to breast feed while receiving treatment on the study or within 6 months of the last dose of study treatment).
- Male or females of reproductive potential who are unwilling to employ adequate contraception during treatment and for 6 months after pirtobrutinib.
- Evidence of Richter transformation.
- Central nervous system (CNS) involvement of CLL/SLL (e.g., any parenchymal, leptomeningeal, cerebrospinal fluid \[CSF\], cranial or spinal nerve root involvement).
- Active uncontrolled autoimmune complications (e.g., active autoimmune hemolytic anemia or clinically significant immune thrombocytopenia).
- Receiving any other investigational agent which would be considered as a treatment for the CLL/SLL (with the exception of corticosteroid).
- Any of the following medication requirement or recent use:
- Requirement of a strong cytochrome P450 (CYP) 3A inhibitor or inducer during the study.
- Use of a strong or moderate CYP3A inhibitor or inducer =\< 7 days prior to registration.
- Requirement of a strong P-glycoprotein 1 (PgP) inhibitor during the study.
- Anticoagulation with a vitamin K antagonist =\< 7 days prior to registration or anticipated use during the study.
- Vaccination with live vaccine =\< 28 days prior to registration.
- NOTE: Because of their effect on CYP3A4, use of any of the following =\< 3 days of study therapy start or planned use during study participation is prohibited:
- +30 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Mayo Cliniclead
Study Sites (1)
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Yucai Wang, MD, PhD
Mayo Clinic in Rochester
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 28, 2022
First Posted
January 10, 2023
Study Start
January 31, 2023
Primary Completion (Estimated)
November 11, 2026
Study Completion (Estimated)
September 3, 2030
Last Updated
February 12, 2026
Record last verified: 2026-02