Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Conditions
Keywords
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Ofatumumab
Brief summary
The risk of immunosuppression deters many patients from receiving fludarabine, while combination chemotherapy regimens are poorly tolerated by elderly or infirm chronic lymphocytic leukemia (CLL) patients. Previous studies by our group and others have shown that rituximab is safe and well tolerated when used as a single agent in patients with CLL. In addition, maintenance therapy with rituximab was well tolerated by CLL patients, with probable prolongation of progression-free survival (Hainsworth et al. 2003). Based on pre clinical and clinical studies indicating possible increased efficacy of ofatumumab in patients with CLL, we wish to develop an antibody-only regimen for older patients and patients who refuse fludarabine-based regimens.
Interventions
DRUGOfatumumab
IV infusion once weekly for a total of 8 weeks. Patients will visit the study center once weekly to receive their IV infusion of ofatumumab. To reduce the possibility of infusion reactions, the first dose of ofatumumab will be administered at a dose of 300 mg. If the initial 300 mg dose of ofatumumab is well tolerated, without occurrence of any infusion-associated AEs of ≥ grade 3, subsequent doses of ofatumumab (i.e., Week 2 through Week 8) will be at a dose of 2000 mg.
Sponsors
GlaxoSmithKline
SCRI Development Innovations, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. CD20+ B-cell chronic lymphocytic leukemia (B-CLL) or small lymphocytic lymphoma according to NCI criteria (see Appendix B). 2. Previously untreated CLL or small lymphocytic lymphoma (SLL). 3. Patients must require treatment according to NCI-Working Group guidelines (see Appendix C). 4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≤2 (see Appendix A). 5. Laboratory values as follows ≤7 days of initiation of treatment: * Creatinine \<3.0 mg/dL * Aspartate amino transferase (AST) or alanine amino transferase (ALT) and alkaline phosphatase (ALP) must be \<3 x upper limit of normal (ULN) * Total bilirubin \<1.5 x the institutional ULN 6. Patients must be hepatitis B sAg negative. Note: Patients who are HepB sAg negative but are HepB cAb positive (regardless of HepB sAb status) will NOT be allowed. 7. Women of childbearing potential must have a negative serum pregnancy test performed ≤7 days prior to start of treatment. Women of childbearing potential or men with partners of childbearing potential must use effective birth control measures during treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately. 8. Patients ≤ 65 years of age, or patients 18-64 years of age who have declined fludarabine-based regimens, are eligible. 9. Patient must be accessible for treatment and follow-up. 10. Patients must be able to understand the nature of this study, give written informed consent prior to study entry, and comply with study requirements.
Exclusion criteria
1. Previous therapy for CLL/SLL. (Patients who have received steroids or IVIG for autoimmune complications of CLL are eligible). 2. Current active hepatic or biliary disease (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease, per assessment by the treating physician). 3. Active bacterial or viral infection, or infection requiring intravenous antibiotic treatment at the time of accrual. 4. Central nervous system lymphoma/CLL. 5. Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (i.e., Richters transformation). 6. History of other malignancy within 2 years of study entry which could affect compliance with the protocol or interpretation of results. Patients with a history of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix, low grade, early-stage, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ (DCIS) of the breast treated with curative intent, are generally eligible. These cases should be discussed with the study chair or study co-chair prior to enrollment. 7. Patients who are HepB sAg positive and/or HepB cAb positive. 8. Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements. 9. Any condition that would prevent patient comprehension of the nature of, and risk associated with, the study. 10. A serious underlying medical condition that would impair the ability of the patient to receive protocol treatment. 11. A major surgical procedure, open biopsy, or significant traumatic injury ≤28 days of beginning treatment, or anticipation of the need for major surgery during the course of the study. 12. Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to visit 1, whichever is longer. Patients may not receive any other investigational or anti-cancer treatments while participating in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | 18 months | The Number of Patients Who Experience an Objective Benefit From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | 18 months | To assess the overall response rate of patients with previously untreated CLL or SLL receiving ofatumumab. |
| Number of Complete Responses | 18 Months | The Number of Patients Who Experience a Complete Response From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions |
| Number of Partial Responses | 18 Months | The Number of Patients Who Experience a Partial Response From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions |
| Safety of the Treatment Regimen | 18 Months | Listing of all non-serious Adverse Events ocurring in 5% of patients or more |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ofatumumab 1000mg Ofatumumab 300mg IV Day 1 followed by ofatumumab 1000mg weekly for a total of 8 weeks
Ofatumumab: IV infusion once weekly for a total of 8 weeks. Patients will visit the study center once weekly to receive their IV infusion of ofatumumab. To reduce the possibility of infusion reactions, the first dose of ofatumumab will be administered at a dose of 300 mg. If the initial 300 mg dose of ofatumumab is well tolerated, without occurrence of any infusion-associated AEs of ≥ grade 3, subsequent doses of ofatumumab (i.e., Week 2 through Week 8) will be at a dose of 2000 mg. | 33 |
| Ofatumumab 2000mg Ofatumumab 300mg IV Day 1 followed by ofatumumab 2000mg weekly for a total of 8 weeks
Ofatumumab: IV infusion once weekly for a total of 8 weeks. Patients will visit the study center once weekly to receive their IV infusion of ofatumumab. To reduce the possibility of infusion reactions, the first dose of ofatumumab will be administered at a dose of 300 mg. If the initial 300 mg dose of ofatumumab is well tolerated, without occurrence of any infusion-associated AEs of ≥ grade 3, subsequent doses of ofatumumab (i.e., Week 2 through Week 8) will be at a dose of 2000 mg. | 44 |
| Total | 77 |
Baseline characteristics
| Characteristic | Ofatumumab 1000mg | Ofatumumab 2000mg | Total |
|---|---|---|---|
| Age, Continuous | 75 years | 69 years | 72 years |
| Region of Enrollment United States | 33 participants | 44 participants | 77 participants |
| Sex: Female, Male Female | 17 Participants | 19 Participants | 36 Participants |
| Sex: Female, Male Male | 16 Participants | 25 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 32 / 33 | 42 / 44 |
| serious Total, serious adverse events | 3 / 33 | 2 / 44 |
Outcome results
Primary
Overall Response Rate (ORR)
The Number of Patients Who Experience an Objective Benefit From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: 18 months
Population: All patients who were evaluable for a response assessment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ofatumumab 1000mg | Overall Response Rate (ORR) | 15 participants |
| Ofatumumab 2000mg | Overall Response Rate (ORR) | 30 participants |
Secondary
Number of Complete Responses
The Number of Patients Who Experience a Complete Response From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions
Time frame: 18 Months
Population: All patients who were evaluable for a response assessment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ofatumumab 1000mg | Number of Complete Responses | 2 participants |
| Ofatumumab 2000mg | Number of Complete Responses | 0 participants |
Secondary
Number of Partial Responses
The Number of Patients Who Experience a Partial Response From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions
Time frame: 18 Months
Population: All patients who were evaluable for a response assessment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ofatumumab 1000mg | Number of Partial Responses | 13 participants |
| Ofatumumab 2000mg | Number of Partial Responses | 30 participants |
Secondary
Progression-free Survival (PFS)
To assess the overall response rate of patients with previously untreated CLL or SLL receiving ofatumumab.
Time frame: 18 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ofatumumab 1000mg | Progression-free Survival (PFS) | 19.8 months |
| Ofatumumab 2000mg | Progression-free Survival (PFS) | 32.5 months |
Secondary
Safety of the Treatment Regimen
Listing of all non-serious Adverse Events ocurring in 5% of patients or more
Time frame: 18 Months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Hypokalemia | 1 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Dizziness | 5 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | White blood cell decreased | 10 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Hyperhidrosis | 6 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Blood bilirubin increased | 2 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Hypocalcemia | 4 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Cough | 5 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Oral pain | 1 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Fatigue | 12 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Respiratory, thoracic and mediastinal disorders | 3 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Diarrhea | 8 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Abdominal pain | 2 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Weight loss | 2 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Allergic rhinitis | 3 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Neutrophil count decreased | 7 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Anorexia | 2 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Allergic reaction | 14 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Back pain | 2 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Dyspnea | 6 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Fever | 2 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Non-cardiac chest pain | 1 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Gastrointestinal disorders - Other, unknown | 3 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Hyperglycemia | 4 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Headache | 4 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Anemia | 14 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Hypertension | 3 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Edema | 8 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Hyponatremia | 4 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Aspartate aminotransferase increased | 6 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Dysgeusia | 2 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Nausea | 3 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Flushing | 1 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Infections and infestations - Other, unspecified | 6 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Gastroesophageal reflux disease | 3 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Pain | 9 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Hypoglycemia | 2 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Peripheral sensory neuropathy | 2 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Musculoskeletal and connective tissue disorders | 2 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Pruritus | 4 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Skin and subcutaneous tissue disorders - Other | 4 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Constipation | 2 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Upper respiratory infection | 0 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Platelet count decreased | 13 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Vomiting | 1 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Insomnia | 3 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Alanine aminotransferase increased | 2 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Urinary frequency | 1 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Blurred vision | 4 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Psychiatric disorders - Other, unspecified | 5 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Bruising | 1 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Rash | 7 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Chills | 1 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Arthralgia | 4 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Creatinine increased | 1 participants |
| Ofatumumab 1000mg | Safety of the Treatment Regimen | Infusion related reaction | 1 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Creatinine increased | 3 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Infusion related reaction | 3 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Urinary frequency | 3 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Weight loss | 2 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Hypocalcemia | 5 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Aspartate aminotransferase increased | 2 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Respiratory, thoracic and mediastinal disorders | 5 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Non-cardiac chest pain | 6 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Hypokalemia | 3 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Nausea | 11 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Fatigue | 21 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Allergic reaction | 16 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Anemia | 13 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Pain | 14 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Platelet count decreased | 10 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Rash | 16 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | White blood cell decreased | 9 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Cough | 13 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Diarrhea | 9 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Neutrophil count decreased | 10 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Dyspnea | 9 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Hyperglycemia | 11 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Edema | 6 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Infections and infestations - Other, unspecified | 7 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Peripheral sensory neuropathy | 11 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Constipation | 10 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Insomnia | 9 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Psychiatric disorders - Other, unspecified | 7 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Arthralgia | 7 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Dizziness | 5 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Hyperhidrosis | 4 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Blood bilirubin increased | 6 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Oral pain | 7 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Pruritus | 3 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Abdominal pain | 4 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Allergic rhinitis | 3 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Anorexia | 4 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Back pain | 4 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Fever | 4 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Gastrointestinal disorders - Other, unknown | 3 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Headache | 2 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Hypertension | 3 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Hyponatremia | 2 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Dysgeusia | 3 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Flushing | 4 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Gastroesophageal reflux disease | 2 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Hypoglycemia | 3 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Musculoskeletal and connective tissue disorders | 3 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Skin and subcutaneous tissue disorders - Other | 1 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Upper respiratory infection | 5 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Vomiting | 4 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Alanine aminotransferase increased | 2 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Blurred vision | 0 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Bruising | 3 participants |
| Ofatumumab 2000mg | Safety of the Treatment Regimen | Chills | 3 participants |