Combination treatment for untreated chronic lymphocytic leukemia and small lymphocytic lymphoma

A Phase Ib Study Evaluating the Safety and Efficacy of Tafasitamab, Acalabrutinib, and Obinutuzumab in Previously Untreated Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

This study is testing a new combination of three medications to see if it can help people with untreated chronic lymphocytic leukemia or small lymphocytic lymphoma feel better and live longer.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 27 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: OHSU Knight Cancer Institute (Academic / other)
• Drugs / interventions: obinutuzumab, Tafasitamab, Acalabrutinib, prednisone
• Locations: 1 site (Portland, Oregon)
• Trial ID: NCT05943496 on ClinicalTrials.gov

What this trial studies

This phase Ib trial evaluates the safety and effectiveness of a combination of tafasitamab, acalabrutinib, and obinutuzumab in patients with previously untreated chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). The study aims to assess the treatment's ability to achieve minimal residual disease negativity and early indications of efficacy. Participants will receive the medications through intravenous and oral routes over multiple cycles, with regular monitoring through blood samples and imaging. The trial also includes exploratory objectives to analyze progression-free survival, overall survival, and quality of life outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a confirmed diagnosis of previously untreated CLL or SLL.

Not a fit: Patients with prior treatment for CLL or SLL or those who do not meet the eligibility criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a more effective option for patients with previously untreated CLL and SLL, potentially improving survival rates.

How similar studies have performed: Other studies have shown promising results with similar combinations of therapies for CLL, indicating potential for success in this approach.

Eligibility criteria

Participant 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/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

FOR PARTICIPANTS WITH SLL ONLY:

* 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

Participant Exclusion Criteria

* 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

Where this trial is running

Portland, Oregon

• OHSU Knight Cancer Institute — Portland, Oregon, United States (Recruiting)

Study contacts

• Principal investigator: Stephen E Spurgeon — OHSU Knight Cancer Institute

Conditions Chronic Lymphocytic Leukemia