Tafasitamab, Acalabrutinib, and Obinutuzumab for the Treatment of Previously Untreated Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

Phase 1

Recruiting

• Conditions: Chronic Lymphocytic Leukemia
• Interventions: Drug: Acalabrutinib; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: Echocardiography; Biological: Obinutuzumab; Other: Questionnaire Administration; Biological: Tafasitamab

• Registration Number: NCT05943496
• Lead Sponsor: OHSU Knight Cancer Institute

Brief Summary

This phase Ib trial tests the safety and effectiveness of tafasitamab, acalabrutinib, and obinutuzumab in treating patients with previously untreated chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). CLL and SLL are types of cancer that develops from a specific white blood cell called B cells or B lymphocytes. Tafasitamab and obinutuzumab are monoclonal antibodies that may interfere with the ability of cancer cells to grow and spread. Acalabrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cell cancers such as CLL at abnormal levels. This may help keep cancer cells from growing and spreading. Giving tafasitamab, acalabrutinib, and obinutuzumab may kill more cancer cells in patients with previously untreated CLL and SLL.

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 or SLL.

IV. Associations between molecular correlates and determinants of CLL/SLL 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 Timeline

• Study First Submitted: 2023-07-05
• Study First Submitted QC: 2023-07-05
• Study First Posted: 2023-07-13
• Study Start: 2023-10-02
• Status Verified: 2023-11
• Last Update Submitted: 2024-07-19
• Last Update Posted: 2024-07-23
• Primary Completion: 2026-01-01
• Study Completion: 2027-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (tafasitamab, obinutuzumab, acalabrutinib)	Biospecimen Collection	See Detailed DescriptionPatients 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.
Treatment (tafasitamab, obinutuzumab, acalabrutinib)	Bone Marrow Aspiration	See Detailed DescriptionPatients 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.
Treatment (tafasitamab, obinutuzumab, acalabrutinib)	Computed Tomography	See Detailed DescriptionPatients 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.
Treatment (tafasitamab, obinutuzumab, acalabrutinib)	Bone Marrow Biopsy	See Detailed DescriptionPatients 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.
Treatment (tafasitamab, obinutuzumab, acalabrutinib)	Echocardiography	See Detailed DescriptionPatients 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.
Treatment (tafasitamab, obinutuzumab, acalabrutinib)	Obinutuzumab	See Detailed DescriptionPatients 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.
Treatment (tafasitamab, obinutuzumab, acalabrutinib)	Questionnaire Administration	See Detailed DescriptionPatients 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.
Treatment (tafasitamab, obinutuzumab, acalabrutinib)	Tafasitamab	See Detailed DescriptionPatients 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.
Treatment (tafasitamab, obinutuzumab, acalabrutinib)	Acalabrutinib	See Detailed DescriptionPatients 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.

Primary Outcome Measures

Name	Time	Method
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.	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 blood	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.

Secondary Outcome Measures

Name	Time	Method
Objective response rate (ORR)	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.	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.

Trial Locations

Locations (1)

OHSU Knight Cancer Institute; 🇺🇸 Portland, Oregon, United States