Tafasitamab, Acalabrutinib, and Obinutuzumab for Untreated CLL/SLL
This study is testing a combination of three drugs—tafasitamab, acalabrutinib, and obinutuzumab—for people with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who haven't received treatment before. CLL and SLL are cancers of certain white blood cells. Tafasitamab and obinutuzumab are antibodies that may stop cancer cells from growing. Acalabrutinib is a kinase inhibitor, meaning it blocks a protein (BTK) that helps cancer cells grow. The main goals are to see how safe this drug combination is and if it can reduce the amount of cancer cells in the blood. This study is currently unclear on its recruitment status and plans to enroll 27 participants.
- Study design
- This is an interventional study, meaning participants will receive specific treatments. It plans to enroll 27 participants.
- What's involved
- You would receive obinutuzumab and tafasitamab intravenously (through a vein) and acalabrutinib by mouth. You would also have blood draws and CT scans throughout the trial, which repeats every 28 days for up to 12 cycles.
- Compensation
- Not stated in the trial record.
- Follow-up
- The study will measure how many patients achieve minimal residual disease negativity for up to 2 years after starting treatment.
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NCT05943496
Tafasitamab, Acalabrutinib, and Obinutuzumab for the Treatment of Previously Untreated Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma
Recruiting
PHASE1Ages 18+InterventionalTreatmentOHSU Knight Cancer InstituteInvestigator-initiated
~27 participants
Updated 2025-11-06 on ClinicalTrials.gov
What's tested:AcalabrutinibBiospecimen CollectionBone Marrow AspirationBone Marrow BiopsyComputed TomographyEchocardiography
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Incidence of dose limiting toxicities (DLTs)
Measured over From first dose of tafasitamab (cycle 2, day 1) to end of cycle 6 (C6D28) up to 2 years. (cycle length = 28 days)
+1 more outcome measured
Conditions
Where it's being run
1 sites across 1 statesOregon1
Study leadership
- Stephen E Spurgeon · PRINCIPAL_INVESTIGATOR · OHSU Knight Cancer Institute
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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/SLL. Diagnosis must be confirmed by peripheral blood flow cytometry or lymph node biopsy 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 within the 7 days before the 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
Previous or concurrent diagnosis of any other hematologic malignancy
Any previous CLL-directed treatment. Use of 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 after 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
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
What this trial measures
- Incidence of dose limiting toxicities (DLTs)From first dose of tafasitamab (cycle 2, day 1) to end of cycle 6 (C6D28) up to 2 years. (cycle length = 28 days)
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.
- Proportion of patients that achieve minimal residual disease (MRD) negativity in peripheral bloodFrom 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.(cycle length = 28 days)
MRD negativity in patients reported using the efficacy set. Point estimate, along with exact two-sided 95% confidence interval (CI) reported.