- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05943496
Tafasitamab, Acalabrutinib, and Obinutuzumab for the Treatment of Previously Untreated Chronic Lymphocytic Leukemia
A Phase Ib Study Evaluating the Safety and Efficacy of Tafasitamab, Acalabrutinib, and Obinutuzumab in Previously Untreated Chronic Lymphocytic Leukemia
Study Overview
Status
Conditions
Detailed Description
PRIMARY OBJECTIVE:
I. Evaluate safety and minimal residual disease negativity.
SECONDARY OBJECTIVE:
I. Evaluate early indications of efficacy as response.
EXPLORATORY OBJECTIVES:
I. Determine progression-free survival. II. Determine overall survival. III. Define the population based on molecular correlates and determinants of CLL.
IV. Associations between molecular correlates and determinants of CLL and response.
V. Patient reported quality of life (QOL) outcomes.
OUTLINE:
Patients receive obinutuzumab intravenously (IV) over a rate titrated up to 400 mg/hour on days 1, 2, 8, and 15 for cycle 1 then on day 1 for cycles 2-6 and tafasitamab IV over 1.5-2 hours on days 1, 4, 8, 15, and 22 for cycle 2, on days 1, 8, 15, and 22 for cycles 3-4, and on days 1 and 15 for cycles 5-7. Patients also receive acalabrutinib orally (PO) twice daily (BID) of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and computed tomography (CT) scans throughout the trial. Patients may undergo an echocardiography (ECHO) at baseline as clinically indicated and may also undergo bone marrow biopsy and/or aspiration at baseline and/or follow-up.
After completion of study treatment, patients are followed up every 3 months for 2 years.
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
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Oregon
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Portland, Oregon, United States, 97239
- Recruiting
- OHSU Knight Cancer Institute
-
Contact:
- OHSU Knight Cancer Clinical Trials Hotline
- Phone Number: 503-494-1080
- Email: trials@ohsu.edu
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Principal Investigator:
- Stephen E. Spurgeon
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Written informed consent. Participant or legally authorized representative (LAR) must provide written informed consent prior to any study-specific procedures or interventions
- Age >= 18 years. All genders, races, and ethnic groups will be included
- Ability to swallow and retain oral medication
- Documented previously untreated CLL. Diagnosis must be confirmed by peripheral flow cytometry and made in accordance with international workshop (iw)CLL diagnostic criteria
- Baseline detectable immunoglobulin heavy (IGH) gene signature determined as part of clonoSEQ for minimal residual disease (MRD) testing
Must meet at least 1 criterion for treatment based on iwCLL guidelines
- Evidence of progressive marrow failure as manifested by the onset or worsening of anemia and/or thrombocytopenia, or
- Massive (i.e., lower edge of spleen >= 6 cm below the left costal margin), progressive, or symptomatic splenomegaly, or
- Massive (i.e., >= 10 cm in the longest diameter), progressive, or symptomatic lymphadenopathy, or
- Progressive lymphocytosis in the absence of infection, with an increase in blood absolute lymphocyte count (ALC) > 50% over a 2 month period, or lymphocyte doubling time of < 6 months (as long as initial ALC was >= 30,000/uL), or
- Autoimmune anemia and / or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy, or
Constitutional symptoms, defined as any one or more of the following disease related symptoms or signs occurring in the absence of evidence of infection:
- Unintentional weight loss of >= 10% within the previous 6 months, or
- Significant fatigue (grade >= 2), or
- Fevers > 100.5°F or 38.0°C for >= 2 weeks, or
- Night sweats for > 1 month
- Presence of measurable lymphadenopathy, defined as the presence of > 1 nodal lesion that measures > 2.0 cm in the longest diameter (LD) and > 1.0 cm in the longest perpendicular diameter (LPD) as assessed by computed tomography (CT) or magnetic resonance imaging (MRI)
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Life expectancy of greater than 12 months, as estimated by the treating physician or investigator
- Absolute neutrophil count (ANC) > 1,000/mm^3 (uL)
- Platelet count > 50,000/mm^3 (uL).
- Serum creatinine =< 2 x upper limit of normal (ULN) or creatinine clearance (CrCl) >= 40 mL/min by Cockcroft-Gault
- Aspartate aminotransferase (AST) =< 3 x ULN
- Alanine aminotransferase (ALT) =< 3 x ULN
- Alkaline phosphatase (ALP) =< 3 x ULN
- Total bilirubin =< 2.5 x ULN unless documented history of Gilbert's syndrome
Negative for hepatitis C infection and chronic hepatitis B infection
- Participants with positive serology for hepatitis C virus (HCV) must have been tested for HCV ribonucleic acid (RNA) and are eligible only in the case of negative HCV RNA by polymerase chain reaction (PCR) testing
- Participants must be hepatitis B virus (HBV) negative by serology. Participants with occult or prior HBV infection (defined as negative hepatitis B [HB] surface antigen [sAg] and positive serology testing for anti-HBV core antigen [cAb]) may be included if HBV deoxyribonucleic acid (DNA) was undetectable by PCR, provided that they are willing to undergo monthly ongoing DNA testing. Antiviral prophylaxis may be administered as per institutional guidelines
- Participants who have protective HBV titers of HB surface antibody (sAb) (HBsAb positive, HBcAb negative, and HBsAg negative) after vaccination or previously cured hepatitis B are eligible
- Individuals with childbearing potential must have documented negative pregnancy test at least 7 days prior to start of any treatment drug and must commit to the use of study approved methods of contraception during study treatment and for 6 months after the last dose of obinutuzumab
- Individuals that can contribute sperm for the conception of a child must commit to the use of study approved methods of contraception during the trial period and for 6 months after the last dose of obinutuzumab. Such individuals must also refrain from donation of sperm during study treatment and for 6 months after the last dose of obinutuzumab
- Individuals of reproductive and lactating potential must agree to stop breastfeeding and refrain from donation of ova from the start of study treatment (cycle [C]1 day [D]1) and for 6 months after the last dose of obinutuzumab
Exclusion Criteria:
- Previous or concurrent diagnosis of any other hematologic malignancy
- Any previous CLL-directed treatment. Prior corticosteroids (or ongoing prednisone =< 20 mg daily, or equivalent) for symptom control are permitted. Enrollment will be considered for those individuals that can taper ongoing use of a corticosteroid at > 20 mg daily to 0 mg within 14 days of C1D1
Known history of hypersensitivity to
- Humanized or murine monoclonal antibodies or products
- A CD19 or CD20 antibody
- Tafasitamab
- Acalabrutinib
- Receipt of live vaccine within 14 days of trial enrollment
- Prior history of any solid malignancy, unless disease-free for over 2 years, exclusive of any prior history of squamous cell carcinoma of the skin or cervix, basal cell carcinoma of the skin, transitional cell urothelial carcinoma, prostate cancer, or early-stage melanoma. Exceptions will be considered, at the discretion of the investigator, if the prior treatment (i.e., within 2 years) is not expected to confound the results of this study
- Patients with history of confirmed progressive multifocal leukoencephalopathy (PML)
- Active autoimmune disease requiring treatment with > 20 mg of prednisone (or prednisone equivalent daily), apart from autoimmune hemolytic anemia or immune thrombocytopenic purpura (ITP).
- Evidence of ongoing systemic bacterial, fungal, or viral infection, except localized fungal infections of skin or nails. NOTE: Participants may be receiving prophylactic antiviral or antibacterial therapies at the discretion of the investigator
- Seropositivity for, or history of active viral infection with, human immunodeficiency virus (HIV)
- Known histological transformation from CLL to an aggressive lymphoma (i.e., Richter's transformation)
- Known bleeding disorders
- Use of warfarin, marcumar, or phenprocoumon unless drug can be discontinued with normalization of international normalized ratio (INR) (e.g., INR < 2, or baseline) within 7 days of C1D1
- Any participant having received agents known to be strong and moderate cytochrome P450 3A inhibitors or inducers within 7 days prior to screening / baseline may require special approval and / or a wash-out period before day 1, at the discretion of the investigator
- Ongoing use of proton pump inhibitors (PPI). PPI must be discontinued 48 hours prior to C1D1
Any severe and / or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
- Symptomatic, or history of documented congestive heart failure (New York [NY] Heart Association functional classification III-IV)
- Left ventricular ejection fraction (LVEF) < 50%
- Poorly controlled atrial fibrillation
- A history of ventricular arrhythmias
- Uncontrolled hypertension (HTN): Defined as hypertension despite the use of > 2 anti-HTN agents at optimal doses
- Myocardial infarction within 6 months of enrollment
- Angina not well-controlled by medication
- Poorly controlled or clinically significant atherosclerotic vascular disease including cerebrovascular accident (CVA), transient ischemic attack (TIA), angioplasty, cardiac / vascular stenting within 6 months of enrollment
- Any other significant medical illness, abnormality, or condition that would, in the investigator's judgement, make the participant inappropriate for study participation or would put the participant at risk
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (tafasitamab, obinutuzumab, acalabrutinib)
Patients receive obinutuzumab IV over a rate titrated up to 400 mg/hour on days 1, 2, 8, and 15 for cycle 1 then on day 1 for cycles 2-6 and tafasitamab IV over 1.5-2 hours on days 1, 4, 8, 15, and 22 for cycle 2, on days 1, 8, 15, and 22 for cycles 3-4, and on days 1 and 15 for cycles 5-7.
Patients also receive acalabrutinib PO BID in each cycle.
Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Patients also undergo blood sample collection and CT throughout the trial.
Patients may undergo an ECHO at baseline as clinically indicated and may also undergo bone marrow biopsy and/or aspiration at baseline and/or follow-up
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Ancillary studies
Undergo blood sample collection
Other Names:
Undergo CT scan
Other Names:
Given PO
Other Names:
Undergo ECHO
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Undergo bone marrow biopsy and/or aspiration
Other Names:
Undergo bone marrow biopsy and/or aspiration
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of patients that achieve minimal residual disease (MRD) negativity in peripheral blood
Time Frame: From first dose of study drug (cycle 1, day 1) to 3, 6, 9, 12 months and 1-3 months after last dose of acalabrutinib up to 2 years
|
MRD negativity in patients reported using the efficacy set.
Point estimate, along with exact two-sided 95% confidence interval (CI) reported.
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From first dose of study drug (cycle 1, day 1) to 3, 6, 9, 12 months and 1-3 months after last dose of acalabrutinib up to 2 years
|
Incidence of dose limiting toxicities (DLTs)
Time Frame: From first dose of tafasitamab (cycle 2, day 1) to end of cycle 6 (C6D28) up to 2 years.
|
Incidences of DLTs, serious AEs, and AEs of special interest experienced during cycle 2-6 evaluated.
The severity of the AE assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 5. The international working chronic lymphocytic leukemia (iwCLL) grading system for hematological toxicities also utilized.
Incidence and type of DLT reported.
|
From first dose of tafasitamab (cycle 2, day 1) to end of cycle 6 (C6D28) up to 2 years.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective response rate (ORR)
Time Frame: From cycle 1, day 1 to any complete response (CR) or partial response (PR) through cycle 12 up to 2 years. Each cycle is 28 days.
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Defined by the iwCLL.
ORR, the sum of CR + PR, estimated using the efficacy set.
ORR point estimate at end of treatment along with exact two-sided 95% CI reported.
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From cycle 1, day 1 to any complete response (CR) or partial response (PR) through cycle 12 up to 2 years. Each cycle is 28 days.
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Stephen E Spurgeon, OHSU Knight Cancer Institute
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Disease Attributes
- Leukemia, B-Cell
- Chronic Disease
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Protein Kinase Inhibitors
- Immunoglobulins
- Obinutuzumab
- Acalabrutinib
- Tyrosine Protein Kinase Inhibitors
Other Study ID Numbers
- STUDY00024507 (Other Identifier: OHSU Knight Cancer Institute)
- NCI-2023-04657 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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