Acalabrutinib and High Frequency Low Dose Subcutaneous Rituximab in Patients With Previously Untreated Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma

NCT03788291 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: ULYM18086
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this research study is to find out if the combination of acalabrutinib and high frequency low dose subcutaneous rituximab is safe and effective in patients who have previously untreated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Conditions

Chronic Lymphocytic Leukemia (CLL); Small Lymphocytic Lymphoma (SLL)

Keywords

Chronic Lymphocytic Leukemia (CLL); Small Lymphocytic Lymphoma (SLL); Phase II; Acalabrutinib; Rituximab

Outcome Measures

Primary Outcomes (1)

• Proportion of Subjects With a Complete Response Rate (CR) at 1 Year of Therapy

  To satisfy criteria for a CR, all of the following criteria must be met: * No evidence of new disease * ALC in peripheral blood of \<4 x 109/L * Regression of all target nodal masses to normal size ≤1.5 cm in the LD * Normal spleen and liver size * Regression to normal of all nodal non-target disease and disappearance of all detectable non-nodal, non-target disease * Morphologically negative bone marrow defined as \<30% of nucleated cells being lymphoid cells and no lymphoid nodules in a bone marrow sample (the presence of benign reactive nodules is still compatible with a CR) * Absence of constitutional symptoms * Peripheral blood counts meeting all of the following criteria: * ANC \>1.5 x 109/L without need for exogenous growth factors (e.g., G-CSF) * Platelet count ≥100 x 109/L without need for exogenous growth factors * Hemoglobin ≥110 g/L (11.0 g/dL) without red blood cell transfusions or need for exogenous growth factors (e.g., erythropoietin)

  1 year

Secondary Outcomes (1)

• Proportion of Subjects With Minimal Residual Disease in Peripheral Blood and Bone

  1 year

Study Arms (1)

Acalabrutinib and Rituximab treatment

EXPERIMENTAL

Rituximab: administered 2 times weekly for 6 cycles. Initial dose day 1: 50 mg IV, Then 50 mg SQ thereafter. Acalabrutinib: 100 mg po BID starting on day 8 of cycle 1. * Patients who have attained a complete response who are also MRD negative at cycle 12 will undergo a BM biopsy to confirm CR and MRD negatively. If confirmed, the patient will stop therapy and be followed until disease progression. * Patients not in a MRD negative CR, will continue acalabrutinib. * Repeat response assessments (CTs, MRD testing in blood) will be performed at 24 cycles of therapy for those continuing on acalabrutinib. If both negative the patient will undergo a BM biopsy to confirm CR and MRD negativity. If confirmed, the patient will stop therapy and be followed until disease progression. In the absence of a CR or if MRD +, acalabrutinib may be continued until disease progression, unacceptable toxicity or physician/patient discretion.

Drug: Acalabrutinib; Drug: Rituximab

Interventions

Acalabrutinib DRUG

100 mg by mouth twice a day starting on day 8 of cycle 1

Acalabrutinib and Rituximab treatment

Rituximab DRUG

Administered 2 times weekly for 6 cycles. Initial dose day 1: 50 mg IV, then 50 mg SQ thereafter.

Acalabrutinib and Rituximab treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of B-cell CLL or SLL, with diagnosis established according to IWCLL criteria and documented within medical records. Patients must not have received previous therapy for CLL/SLL
• CLL/SLL that warrants treatment consistent with accepted IWCLL criteria for initiation of therapy. Any one of the following conditions constitutes CLL/SLL that warrants treatment:
• 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/L), 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:
• i. Unintentional weight loss of ≥10% within the previous 6 months, or
• ii. Significant fatigue (≥Grade 2), or
• iii. Fevers \>100.5°F or 38.0°C for ≥2 weeks, or
• iv. Drenching night sweats for \>1 month.
• Adequate organ system function, defined as follows:
• Absolute neutrophil count (ANC) ≥ 0.5x109/L and platelet count ≥ 30x109/L
• Total bilirubin ≤2.5 times the upper limit of normal (ULN) unless due to Gilbert's disease

You may not qualify if:

• Patients receiving cancer therapy (i.e., chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy, surgery).
• a. Systemic corticosteroid therapy started prior to study entry is allowed as clinically warranted. Topical or inhaled corticosteroids are permitted.
• Serologic status reflecting active hepatitis B or C infection. Patients who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR). Those who are hepatitis B surface antigen (HbsAg) positive or hepatitis B PCR positive will be excluded. Subjects who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded.
• Known history of HIV.
• Known histological transformation from CLL to an aggressive lymphoma.
• Evidence of ongoing systemic bacterial, fungal or viral infection, except localized fungal infections of skin or nails. NOTE: Patients may be receiving prophylactic antiviral or antibacterial therapies at investigator discretion.
• Live virus vaccines within 4 weeks prior to C1D1 or during rituximab therapy.
• History of anaphylaxis (excluding infusion related reactions) in association with previous anti-CD20 administration or acalabrutinib.
• 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 (NY Heart Association functional classification III-IV)
• Uncontrolled cardiac arrhythmia (Patients with controlled atrial fibrillation/flutter are eligible)
• Myocardial infarction within 3 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 3 months of enrollment.
• Active bleeding or history of bleeding diathesis (eg, hemophilia or von Willebrand disease).

Sponsors & Collaborators

• University of Rochester: lead

Study Sites (1)

University of Rochester

Rochester, New York, 14642, United States

Location

Related Publications (1)

• Wallace DS, Zent CS, Baran AM, Reagan PM, Casulo C, Rice G, Friedberg JW, Barr PM. Acalabrutinib and high-frequency low-dose subcutaneous rituximab for initial therapy of chronic lymphocytic leukemia. Blood Adv. 2023 Jun 13;7(11):2496-2503. doi: 10.1182/bloodadvances.2022009382.

  PMID: 36689726 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

acalabrutinib; Rituximab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Paul Barr, MD
• Organization: University of Rochester

paul_barr@urmc.rochester.edu

585-273-3258

Study Officials

• Paul Barr

  University of Rochester

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Clinical Trials Office for Wilmot Cancer Institute

Study Record Dates

• First Submitted: December 24, 2018
• First Posted: December 27, 2018
• Study Start: March 25, 2019
• Primary Completion: May 19, 2023
• Study Completion: May 19, 2023
• Last Updated: September 26, 2024
• Results First Posted: September 26, 2024

Record last verified: 2024-09

Locations

US (1)