Trial Outcomes & Findings for Acalabrutinib and High Frequency Low Dose Subcutaneous Rituximab in Patients With Previously Untreated Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (NCT NCT03788291)
NCT ID: NCT03788291
Last Updated: 2024-09-26
Results Overview
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)
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
39 participants
Primary outcome timeframe
1 year
Results posted on
2024-09-26
Participant Flow
Participant milestones
| Measure |
Acalabrutinib and Rituximab Treatment
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.
Acalabrutinib: 100 mg by mouth twice a day starting on day 8 of cycle 1
Rituximab: Administered 2 times weekly for 6 cycles. Initial dose day 1: 50 mg IV, then 50 mg SQ thereafter.
|
|---|---|
|
Overall Study
STARTED
|
38
|
|
Overall Study
COMPLETED
|
38
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Acalabrutinib and High Frequency Low Dose Subcutaneous Rituximab in Patients With Previously Untreated Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma
Baseline characteristics by cohort
| Measure |
Acalabrutinib and Rituximab Treatment
n=38 Participants
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.
Acalabrutinib: 100 mg by mouth twice a day starting on day 8 of cycle 1
Rituximab: Administered 2 times weekly for 6 cycles. Initial dose day 1: 50 mg IV, then 50 mg SQ thereafter.
|
|---|---|
|
Age, Continuous
|
66.5 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
38 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
38 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
38 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 1 yearTo 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)
Outcome measures
| Measure |
Acalabrutinib and Rituximab Treatment
n=38 Participants
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.
Acalabrutinib: 100 mg by mouth twice a day starting on day 8 of cycle 1
Rituximab: Administered 2 times weekly for 6 cycles. Initial dose day 1: 50 mg IV, then 50 mg SQ thereafter.
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|---|---|
|
Proportion of Subjects With a Complete Response Rate (CR) at 1 Year of Therapy
|
0.26 proportion of participants
|
SECONDARY outcome
Timeframe: 1 yearPopulation: This analysis was only performed on participants with a complete response after 12 cycles of treatment. Ten participants had a complete response.
6-color flow cytometry was performed on patients achieving a complete response to evaluate for minimal residual disease.
Outcome measures
| Measure |
Acalabrutinib and Rituximab Treatment
n=10 Participants
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.
Acalabrutinib: 100 mg by mouth twice a day starting on day 8 of cycle 1
Rituximab: Administered 2 times weekly for 6 cycles. Initial dose day 1: 50 mg IV, then 50 mg SQ thereafter.
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|---|---|
|
Proportion of Subjects With Minimal Residual Disease in Peripheral Blood and Bone
|
1.0 proportion or participants
|
Adverse Events
Acalabrutinib and Rituximab Treatment
Serious events: 10 serious events
Other events: 38 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Acalabrutinib and Rituximab Treatment
n=38 participants at risk
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.
Acalabrutinib: 100 mg by mouth twice a day starting on day 8 of cycle 1
Rituximab: Administered 2 times weekly for 6 cycles. Initial dose day 1: 50 mg IV, then 50 mg SQ thereafter.
|
|---|---|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
2.6%
1/38 • 1 year
|
|
Infections and infestations
Lung infection
|
2.6%
1/38 • 1 year
|
|
Infections and infestations
COVID-19 infection
|
10.5%
4/38 • 1 year
|
|
Renal and urinary disorders
Urinary Tract Obstruction
|
2.6%
1/38 • 1 year
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
2.6%
1/38 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
2.6%
1/38 • 1 year
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Leiomyosarcoma
|
2.6%
1/38 • 1 year
|
|
Infections and infestations
Joint Infection
|
2.6%
1/38 • 1 year
|
|
Infections and infestations
Urinary tract infection
|
5.3%
2/38 • 1 year
|
|
Cardiac disorders
Coronary artery disease
|
2.6%
1/38 • 1 year
|
|
Nervous system disorders
Stroke
|
2.6%
1/38 • 1 year
|
Other adverse events
| Measure |
Acalabrutinib and Rituximab Treatment
n=38 participants at risk
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.
Acalabrutinib: 100 mg by mouth twice a day starting on day 8 of cycle 1
Rituximab: Administered 2 times weekly for 6 cycles. Initial dose day 1: 50 mg IV, then 50 mg SQ thereafter.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
5.3%
2/38 • 1 year
|
|
Infections and infestations
COVID-19
|
39.5%
15/38 • 1 year
|
|
Infections and infestations
Pneumonia (non-COVID)
|
13.2%
5/38 • 1 year
|
|
Infections and infestations
Dental Infection
|
5.3%
2/38 • 1 year
|
|
Infections and infestations
Cellulitis
|
7.9%
3/38 • 1 year
|
|
Infections and infestations
Upper respiratory infection
|
31.6%
12/38 • 1 year
|
|
Infections and infestations
Urinary tract infection
|
21.1%
8/38 • 1 year
|
|
Musculoskeletal and connective tissue disorders
arthritis/arthralgias
|
39.5%
15/38 • 1 year
|
|
Musculoskeletal and connective tissue disorders
bruising
|
39.5%
15/38 • 1 year
|
|
Musculoskeletal and connective tissue disorders
hematoma
|
10.5%
4/38 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Myalgias
|
50.0%
19/38 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Rash
|
23.7%
9/38 • 1 year
|
|
Gastrointestinal disorders
Constipation
|
21.1%
8/38 • 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
23.7%
9/38 • 1 year
|
|
Gastrointestinal disorders
Nausea
|
28.9%
11/38 • 1 year
|
|
General disorders
Cough
|
26.3%
10/38 • 1 year
|
|
Nervous system disorders
Dizziness
|
21.1%
8/38 • 1 year
|
|
General disorders
Edema
|
31.6%
12/38 • 1 year
|
|
General disorders
Fatigue
|
36.8%
14/38 • 1 year
|
|
Nervous system disorders
Headache
|
68.4%
26/38 • 1 year
|
|
Injury, poisoning and procedural complications
Infusion reaction
|
63.2%
24/38 • 1 year
|
|
General disorders
Injection site reaction
|
31.6%
12/38 • 1 year
|
|
Cardiac disorders
Sinus bradychardia
|
5.3%
2/38 • 1 year
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place