Chronic Lymphocytic Leukemia and Relapsed and Refractory Mantle Cell Lymphoma
Conditions
Brief summary
This study is plan to assess the safety and efficacy of Acalabrutinib in Indian patients with chronic lymphocytic leukaemia (CLL) and relapsed and refractory mantle cell lymphoma (MCL)
Detailed description
A prospective, multi-centre, phase IV clinical trial of Acalabrutinib capsules in Indian adult patients with chronic lymphocytic leukaemia (CLL) and relapsed and refractory mantle cell lymphoma (MCL). As per recommendation from Indian health authority, the current phase-IV study is planned with the aim to assess the safety and efficacy profile of Acalabrutinib in Indian patients with CLL/SLL, and patients with MCL who have received at least one prior therapy. The data obtained from the study will help to understand the safety and efficacy profile of Acalabrutinib in Indian patients. Patients will be monitored throughout the study period for Adverse Events of Acalabrutinib
Interventions
DRUGAcalabrutinib capsule
The recommended dose of Acalabrutinib is 100 mg given per oral (PO) twice daily
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
None (Open Label)
Intervention model description
A Prospective, Multicentre, Phase-IV study and Clinical trials with a single arm.
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
Patients are eligible to be included in the study only if all of the following inclusion criteria and none of the
Exclusion criteria
apply: 1\. Men and Women aged 18yrs or more. 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0,1, or 2 3. Able to receive all outpatient treatments, all laboratory monitoring, and all radiologic evaluations. 4\. The following laboratory parameters: 1. Absolute neutrophil count (ANC) ≥750 cells/μL or ≥500 cells/μL in patients with documented bone marrow involvement, and independent of growth factor support 07 days before the assessment 2. Platelet count ≥50,000 cells/μL or ≥30,000 cells/μL in patients with documented bone marrow involvement, and without transfusion support 07 days before the assessment 3. Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤2.0 x ULN 4. Total bilirubin ≤1.5 x ULN 5. Estimated creatinine clearance of ≥30 mL/min 5. Refractory disease defined as achieving less than partial response with the most recent treatment within 6 months before study entry 6. Provision of signed, written and dated informed consent prior to any study-specific Procedures 7. The patients of either CLL or MCL: a. CLL patients: i. Treatment naïve or ≥1 prior systemic therapy for CLL ii. Diagnosis of CD20+ CLL that meets published diagnostic criteria (Hallek et al. 2018) iii. An active disease that meets ≥1 of the following iwCLL 2018 criteria for requiring treatment: 1. Evidence of progressive marrow failure as manifested by the development of, or worsening of, anaemia and/or thrombocytopenia. Cut-off levels of Hb \<10 g/dL or platelet counts \<100 × 109/L are generally regarded as an indication for treatment. However, in some patients, platelet counts \<100 × 109/L may remain stable over a long period; this situation does not automatically require therapeutic intervention. 2. Massive (i.e., ≥6 cm below the left costal margin) or progressive or symptomatic splenomegaly. 3. Massive nodes (i.e., ≥10 cm in longest diameter) or progressive or symptomatic lymphadenopathy. 4. Progressive lymphocytosis with an increase of ≥50% over a 2-month period or Lymphocyte Doubling Time (LDT) in \<6 months. LDT can be obtained by linear regression extrapolation of absolute lymphocyte counts obtained at intervals of 2 weeks over an observation period of 2 to 3 months; patients with initial blood lymphocyte counts \<30 × 109/L may require a longer observation period to determine the LDT. Factors contributing to lymphocytosis other than CLL (e.g., infections, steroid administration) should be excluded. 5. Autoimmune complications, including anaemia or thrombocytopenia poorly responsive to corticosteroids. 6. Symptomatic or functional extra-nodal involvement (e.g., skin, kidney, lung, spine). 7. Disease-related symptoms as defined by any of the following: 1. Unintentional weight loss of ≥10% within the previous 06 months. 2. Significant fatigue (i.e., ECOG performance scale 02 or worse; cannot work or unable to perform usual activities). 3. Fever ≥100.5°F or 38.0°C for 02 or more weeks without evidence of infection. 4. Night sweats for ≥1 month without evidence of infection. b. MCL Patients: i. Confirmed MCL with translocation t(11;14) (q13;q32) and/or overexpressed cyclin D1 ii. Measurable nodal disease (one or more lesions measuring ≥2 cm in the longest diameter) iii. Relapsed after, or were refractory to, 1-5 previous treatments
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events of Special Interest (AESI) Including Arrhythmias (Atrial Fibrillation), Anaemia, Hypertension, Bleeding, Infections | Throughout study completion, approximately 198 days (from the Screening Phase [Day 0], Treatment Phase [Days 1-170], and until the Follow-up Phase [28 days after Day 170]) | The AESIs for acalabrutinib, including arrhythmias (atrial fibrillation), anaemia, hypertension, bleeding, and infections, are presented. |
| Second Primary Malignancies | Throughout study completion, approximately 198 days (from the Screening Phase [Day 0], Treatment Phase [Days 1-170], and until the Follow-up Phase [28 days after Day 170]) | The safety of acalabrutinib was investigated by determining the number of second primary malignancies. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response to Treatment | Visit 5 (Day 85) and Visit 8 (Day 170) | The efficacy of acalabrutinib was assessed by measuring the participants' objective response to treatment. Objective response = Complete Response (CR) + Partial Response (PR) + Partial Response with lymphocytosis (PRL). |
| Health Related Quality of Life (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 [EORTC QLQC30] Questionnaire) | From Visit 1 (Day 0), during Visit 5 (Day 85), and at Visit 8 (Day 170) | The EORTC QLQ-C30 is a 30-item questionnaire that measures quality of life in cancer patients. It is divided into several scales: Functioning Scales (Physical, Role, Cognitive, Emotional, and Social), Symptom Scales (Fatigue, Pain, Nausea/Vomiting), Dyspnoea, Sleep Disturbances, Appetite Loss, Diarrhoea, Constipation, Financial Difficulties, and Global Health Status/Quality of Life Scale. Scores range from 0 to 100. A higher score indicates better health related quality of life. The total scores were calculated from the mean of the 13 QLQ-C30 scales (Global Quality of Life Scale and Financial Impact Scale were excluded). Prior to calculating the mean, Symptom Scales were reversed to obtain a uniform direction of all scales. The total score was only calculated if all of the required 13 scale scores were available using scale scores based on the completed items, provided that at least 50% of the items in that scale were completed. |
Countries
India
Participant flow
Pre-assignment details
103 participants were consented and were divided into two groups, participants with CLL/SLL (N=90) and participants with MCL (N=13). Out of these, 100 participants (89 in the CLL/SLL and 11 in the MCL group) were considered in the full analysis set, 03 enrolled participants were discontinued due to withdrawal of the consent form.
Participants by arm
| Arm | Count |
|---|---|
| CCL/SLL Participants were treatment naïve or had received at least one prior therapy | 89 |
| Relapsed and Refractory MCL Participants had received at least one prior therapy | 11 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death, Serious Adverse Event, Screen Failure | 1 | 3 |
| Overall Study | Disease Progression | 2 | 0 |
| Overall Study | Patient Decision | 4 | 2 |
Baseline characteristics
| Characteristic | Relapsed and Refractory MCL | Total | CCL/SLL |
|---|---|---|---|
| Age, Continuous | 60.3 Years STANDARD_DEVIATION 6.9 | 61.6 Years STANDARD_DEVIATION 10.8 | 61.8 Years STANDARD_DEVIATION 11.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 11 Participants | 100 Participants | 89 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 2 Participants | 20 Participants | 18 Participants |
| Sex: Female, Male Male | 9 Participants | 80 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 89 | 2 / 11 |
| other Total, other adverse events | 38 / 89 | 7 / 11 |
| serious Total, serious adverse events | 8 / 89 | 3 / 11 |
Outcome results
Primary
Adverse Events of Special Interest (AESI) Including Arrhythmias (Atrial Fibrillation), Anaemia, Hypertension, Bleeding, Infections
The AESIs for acalabrutinib, including arrhythmias (atrial fibrillation), anaemia, hypertension, bleeding, and infections, are presented.
Time frame: Throughout study completion, approximately 198 days (from the Screening Phase [Day 0], Treatment Phase [Days 1-170], and until the Follow-up Phase [28 days after Day 170])
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CLL/SLL | Adverse Events of Special Interest (AESI) Including Arrhythmias (Atrial Fibrillation), Anaemia, Hypertension, Bleeding, Infections | 0 Events |
| Relapsed and Refractory MCL | Adverse Events of Special Interest (AESI) Including Arrhythmias (Atrial Fibrillation), Anaemia, Hypertension, Bleeding, Infections | 0 Events |
Primary
Second Primary Malignancies
The safety of acalabrutinib was investigated by determining the number of second primary malignancies.
Time frame: Throughout study completion, approximately 198 days (from the Screening Phase [Day 0], Treatment Phase [Days 1-170], and until the Follow-up Phase [28 days after Day 170])
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CLL/SLL | Second Primary Malignancies | 0 Participants |
| Relapsed and Refractory MCL | Second Primary Malignancies | 0 Participants |
Secondary
Health Related Quality of Life (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 [EORTC QLQC30] Questionnaire)
The EORTC QLQ-C30 is a 30-item questionnaire that measures quality of life in cancer patients. It is divided into several scales: Functioning Scales (Physical, Role, Cognitive, Emotional, and Social), Symptom Scales (Fatigue, Pain, Nausea/Vomiting), Dyspnoea, Sleep Disturbances, Appetite Loss, Diarrhoea, Constipation, Financial Difficulties, and Global Health Status/Quality of Life Scale. Scores range from 0 to 100. A higher score indicates better health related quality of life. The total scores were calculated from the mean of the 13 QLQ-C30 scales (Global Quality of Life Scale and Financial Impact Scale were excluded). Prior to calculating the mean, Symptom Scales were reversed to obtain a uniform direction of all scales. The total score was only calculated if all of the required 13 scale scores were available using scale scores based on the completed items, provided that at least 50% of the items in that scale were completed.
Time frame: From Visit 1 (Day 0), during Visit 5 (Day 85), and at Visit 8 (Day 170)
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CLL/SLL | Health Related Quality of Life (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 [EORTC QLQC30] Questionnaire) | Visit 5 Total Score | 56.8 Score on a scale | Standard Deviation 7.88 |
| CLL/SLL | Health Related Quality of Life (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 [EORTC QLQC30] Questionnaire) | Visit 8 Total Score | 57.9 Score on a scale | Standard Deviation 9.34 |
| CLL/SLL | Health Related Quality of Life (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 [EORTC QLQC30] Questionnaire) | Visit 1 Total Score | 56.9 Score on a scale | Standard Deviation 12.52 |
| Relapsed and Refractory MCL | Health Related Quality of Life (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 [EORTC QLQC30] Questionnaire) | Visit 1 Total Score | 57.0 Score on a scale | Standard Deviation 6.46 |
| Relapsed and Refractory MCL | Health Related Quality of Life (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 [EORTC QLQC30] Questionnaire) | Visit 5 Total Score | 57.9 Score on a scale | Standard Deviation 7.21 |
| Relapsed and Refractory MCL | Health Related Quality of Life (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 [EORTC QLQC30] Questionnaire) | Visit 8 Total Score | 58.6 Score on a scale | Standard Deviation 6.76 |
Secondary
Objective Response to Treatment
The efficacy of acalabrutinib was assessed by measuring the participants' objective response to treatment. Objective response = Complete Response (CR) + Partial Response (PR) + Partial Response with lymphocytosis (PRL).
Time frame: Visit 5 (Day 85) and Visit 8 (Day 170)
Population: Full Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CLL/SLL | Objective Response to Treatment | Visit 5: CR | 1 Participants |
| CLL/SLL | Objective Response to Treatment | Visit 5: PR | 53 Participants |
| CLL/SLL | Objective Response to Treatment | Visit 5: PRL | 1 Participants |
| CLL/SLL | Objective Response to Treatment | Visit 5: Objective Response | 55 Participants |
| CLL/SLL | Objective Response to Treatment | Visit 8: CR | 4 Participants |
| CLL/SLL | Objective Response to Treatment | Visit 8: PR | 50 Participants |
| CLL/SLL | Objective Response to Treatment | Visit 8: PRL | 1 Participants |
| CLL/SLL | Objective Response to Treatment | Visit 8: Objective Response | 55 Participants |
| Relapsed and Refractory MCL | Objective Response to Treatment | Visit 8: Objective Response | 4 Participants |
| Relapsed and Refractory MCL | Objective Response to Treatment | Visit 5: CR | 2 Participants |
| Relapsed and Refractory MCL | Objective Response to Treatment | Visit 8: CR | 0 Participants |
| Relapsed and Refractory MCL | Objective Response to Treatment | Visit 5: PR | 3 Participants |
| Relapsed and Refractory MCL | Objective Response to Treatment | Visit 8: PRL | 0 Participants |
| Relapsed and Refractory MCL | Objective Response to Treatment | Visit 5: PRL | 0 Participants |
| Relapsed and Refractory MCL | Objective Response to Treatment | Visit 8: PR | 4 Participants |
| Relapsed and Refractory MCL | Objective Response to Treatment | Visit 5: Objective Response | 5 Participants |