Ofatumumab Plus Bendamustine in Frontline and Relapsed Chronic Lymphocytic Leukaemia (CLL)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01520922
First received: January 19, 2012
Last updated: August 7, 2014
Last verified: March 2014
  Purpose

This is a Phase II, open label, single arm, multi-centre study investigating the safety and efficacy of ofatumumab plus bendamustine in subjects with untreated or relapsed CLL.

Each subject from the screening phase who is willing to participate in the study and is found eligible according to the inclusion and exclusion criteria will enter the treatment phase and will receive a maximum of 6 Cycles of study treatment (ofatumumab plus bendamustine). All subjects will receive 3 Cycles of study treatment (Cycles 1, 2 and 3). Eligibility to receive study treatment for Cycles 4, 5 and 6 will be assessed following the 3rd Cycle. Subjects who have achieved at least stable disease with acceptable toxicity following 3 Cycles of treatment will be eligible to continue to receive study treatments for a maximum of 3 further Cycles. In case of progressive disease, at, or at any time after the start of Cycle 4, subjects must discontinue further study treatment and move into the study's follow-up period.

During the treatment phase, all eligible subjects will be allocated to receive the following study treatments:

  1. Subjects with Untreated CLL: Up to 6 monthly intravenous infusions of ofatumumab (Cycle 1: 300 mg Day 1 and 1000 mg Day 8; subsequent Cycles: 1000 mg at Day 1 every 28 Days) in combination with up to 6 Cycles of intravenously infused bendamustine (90 mg/m2, Days 1 and 2, every 28 Days).
  2. Subjects with Relapsed CLL: Up to 6 monthly intravenous infusions of ofatumumab (Cycle 1: 300 mg Day 1 and 1000 mg Day 8; subsequent Cycles: 1000 mg at Day 1 every 28 Days) in combination with up to 6 Cycles of intravenously infused bendamustine (70 mg/m2, Days 1 and 2, every 28 Days).

The studies primary endpoint is overall response rate (ORR) as determined by Investigator evaluation. The ORR is the percentage of subjects achieving an objective response (i.e., partial response or better), using the IWCLL updated NCI-WG guidelines. Response assessments are planned at the following time-points: After 3 Cycles of ofatumumab plus bendamustine treatment, after 6 Cycles of ofatumumab plus bendamustine treatment and after the last dose, if not after 6 cycles, of ofatumumab plus bendamustine treatment.

Follow-up assessments will be performed every 3 months following the last study treatment. The follow-up period will last for a maximum of 3 years. Response evaluation assessments to determine subject response or progression will be performed during the follow-up period, according to the IWCLL updated NCI-WG guidelines. Following progression, only survival status and details concerning the subject's next CLL therapy will be recorded.


Condition Intervention Phase
Leukaemia, Lymphocytic, Chronic
Biological: Ofatumumab
Drug: Bendamustine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II, Multi-centre Study Investigating the Safety and Efficacy of Ofatumumab and Bendamustine Combination in Patients With Untreated or Relapsed Chronic Lymphocytic Leukaemia (CLL)

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Participants With Overall Response (OR), as Assessed by the Investigator [ Time Frame: From the start of study treatment until 3 months after the last dose of study treatment ] [ Designated as safety issue: No ]
    OR is defined as the number of participants achieving an objective response (complete response [CR], CR with incomplete bone marrow recovery [CRi], partial response [PR], and nodular PR [nPR]), after 3 cycles, after 6 cycles, and after the last dose of ofatumumab and bendamustine treatment. CR (all the criteria at least 2 months after last treatment): no lymphadenopathy (Ly)/ hepatomegaly/ splenomegaly/ constitutional symptoms; neutrophils >1500 per microliter (µL), platelets (PL) >100,000/µL, hemoglobin (Hb) >11 grams/deciliter (g/dL), lymphocytes (LC) <4000/µL, bone marrow (BM) sample must be normocellular for age, <30% LC, no lymphoid nodule. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. PR: >=50% decrease in LC, Ly, size of liver and spleen and at least one of the following results: PL >100,000/µL or 50% improvement over Baseline (BL), Hb >11 g/dL or 50% improvement over BL, LC <4000/µL. nPR: persistent nodules BM.


Secondary Outcome Measures:
  • Number of Participants With Overall Response (OR) With Computed Tomography (CT) Scan (CT Scan) Assessment, as Assessed by the Investigator [ Time Frame: From the start of study treatment until 3 months after the last dose of study treatment ] [ Designated as safety issue: No ]
    OR is defined as the number of participants achieving an objective response (complete response [CR], CR with incomplete bone marrow recovery [CRi], partial response [PR], and nodular PR [nPR]), after 3 cycles, after 6 cycles, and after the last dose of ofatumumab and bendamustine treatment. CR (all the criteria at least 2 months after last treatment): no lymphadenopathy (Ly)/ hepatomegaly/ splenomegaly/ constitutional symptoms; neutrophils >1500 per microliter (µL), platelets (PL) >100,000/µL, hemoglobin (Hb) >11 grams/deciliter (g/dL), lymphocytes (LC) <4000/µL, bone marrow (BM) sample must be normocellular for age, <30% LC, no lymphoid nodule. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. PR: >=50% decrease in LC, Ly, size of liver and spleen and at least one of the following results: PL >100,000/µL or 50% improvement over Baseline (BL), Hb >11 g/dL or 50% improvement over BL, LC <4000/µL. nPR: persistent nodules BM.

  • Number of Participants With Complete Response (CR) With and Without a CT Scan Assessment After the Last Dose of Study Treatment, as Assessed by the Investigator [ Time Frame: From the start of study treatment until 3 months after the last dose of study treatment ] [ Designated as safety issue: No ]
    Response was determined according to the IWCLL updated NCI-WG guidelines 2008. CR requires all of the following criteria at least 2 months after the last treatment: no lymphadenopathy (Ly)/ hepatomegaly/ splenomegaly/ constitutional symptoms; neutrophils >1500/µL, platelets (PL) >100,000/µL, hemoglobin (Hb) >11.0 g/dL, lymphocytes (LC) <4000/µL, bone marrow (BM) sample must be normocellular for age, <30% LC, no lymphoid nodule.

  • Progression-free Survival (PFS) [ Time Frame: From the start of study treatment until earliest date of disease progression or death (up to 3 years after the last dose of study treatment) ] [ Designated as safety issue: No ]
    PFS is defined as the interval of time between the date of the first administration of study treatment and the earlier of the date of disease progression (PD) and the date of death due to any cause. PD requires at least one of the following:new lesion or increase by >=50% from BL in LC, Ly, size of liver and spleen, PL >= 50% decrease from BL, or to <100,000/uL secondary to CLL, Hb decrease of >2 g/dL from BL or to <10 g/dL secondary to CLL, CLL- transformation. Response was determined according to the IWCLL updated NCI-WG guidelines 2008. Participants who have neither progressed or died at the time of analysis were censored at the date of the last adequate assessment. If there was more than 1 scheduled visit missed, PFS is censored at the last adequate assessment of response. An adequate assessment is defined as an assessment where the investigator determined a response of CR, CRi, nPR, PR, or stable disease (SD). PFS data are not yet mature and the median PFS has not been reached.

  • Overall Survival (OS) [ Time Frame: From the start of study treatment to the date of death due to any cause (up to 3 years after the last dose of study treatment) ] [ Designated as safety issue: No ]
    OS is defined as the interval of time between the date of the first administration of study treatment and the date of death due to any cause. For participants who did not die, time of death was censored at the date of last contact. OS data are not yet mature and the median OS has not been reached.

  • Time to Response [ Time Frame: From the start of study treatment to the first response (CR, CRi, nPR, or PR) (up to 3 Month Follow-up (F/U) visit) ] [ Designated as safety issue: No ]
    Time to response is defined as time from date of the first administration of study treatment to the first response (CR, CRi, nPR, or PR). Response was determined according to the IWCLL updated NCI-WG guidelines 2008. CR: all of the following criteria at least 2 months after last treatment: no lymphadenopathy (Ly)/ hepatomegaly/ splenomegaly/ constitutional symptoms; neutrophils >1500 per microliter (µL), platelets (PL) >100,000/µL, hemoglobin (Hb) >11.0 grams/deciliter (g/dL), lymphocytes (LC) <4000/µL, bone marrow (BM) sample must be normocellular for age, <30% LC, no lymphoid nodule. CRi: CR criteria, persistent anemia/ thrombocytopenia/ neutropenia unrelated to CLL but related to drug toxicity. nPR: persistent nodules BM. PR: >=50% decrease in LC, Ly, size of liver and spleen and at least one of the following results: PL >100,000/µL or 50% improvement over Baseline (BL), Hb >11.0 g/dL or 50% improvement over BL, LC <4000/µL.

  • Duration of Response [ Time Frame: From time of initial response (CR, CRi, nPR, or PR) to disease progression or death, whichever came first (up to 3 years after the last doseof study treatment) ] [ Designated as safety issue: No ]
    The duration of response is defined as the time from the initial response (CR, CRi, nPR, or PR) to the first documented sign of disease progression (PD) or death due to any cause. PD requires at least one of the following: new lesion or increase by >=50% from Baseline in lymphocytes (LC) with at least 5000B-lymphocytes per microliter (5.0 x 10^9/L), lymphadenopathy (Ly), size of liver and spleen, platelets (PL) >= 50% decrease from Baseline, or to <100,000/uL secondary to CLL, hemoglobin (Hb) decrease of >2 g/dL from Baseline or to <10 g/dL secondary to CLL, CLL- transformation, cytopenia after treatment. Response was determined according to the IWCLL updated NCI-WG guidelines 2008.

  • Time to Progression [ Time Frame: From the start of study treatment to disease progression (up to 3 years after the last dose of study treatment) ] [ Designated as safety issue: No ]
    Time to progression is defined as the time from the date of the first administration of study treatment to disease progression (PD). PD requires at least one of the following: new lesion or increase by >=50% from Baseline in lymphocytes (LC) with at least 5000 B-lymphocytes per microliter (5.0 x 10^9/L), lymphadenopathy (Ly), size of liver and spleen, platelets (PL) >= 50% decrease from Baseline, or to <100,000/uL secondary to CLL, hemoglobin (Hb) decrease of >2 g/dL from Baseline or to <10 g/dL secondary to CLL, CLL- transformation, cytopenia after treatment. Response was determined according to the IWCLL updated NCI-WG guidelines 2008.Time to progression data are not yet mature and the median time to progression has not been reached.

  • Time to Next Therapy [ Time Frame: From the start of study treatment until the start of the next anti-CLL therapy (up to 3 years after the last dose of study treatment) ] [ Designated as safety issue: No ]
    Time to next therapy is defined as the time from the date of the first administration of study treatment until the start of the next anti-CLL therapy.

  • Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) [ Time Frame: From first dose of study medication to 60 days after the last dose of study medication (if the event is considered as an AE), or up to 3 years after the last dose of study treatment or until the time of the next anti-CLL therapy, if considered a SAE ] [ Designated as safety issue: No ]
    An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs.

  • Mean Change From Baseline in the Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM [ Time Frame: Baseline and last study visit/withdrawal visit (up to 3 years after the last dose of study treatment) ] [ Designated as safety issue: No ]
    Immunoglobulins, or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Low levels indicate immuno-suppression. IgA, IgG, and IgM were measured in the blood samples of the participants. Baseline IgA, IgG, and IgM values are the last pre-dose assessment values performed on cycle 1 Day 1. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

  • Change From Baseline in Cluster of Differentiation (CD) CD5+CD19+ Cell Counts at Screening, 3-Month Follow-up, and 6-Month Follow-up [ Time Frame: Screening, 3-Month Follow-up, and 6-Month Follow-up ] [ Designated as safety issue: No ]
    CD5+ CD19+ cells were counted by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus. Baseline CD5+ CD19+ cell count value is the last pre-dose assessment values performed on cycle 1 Day 1. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

  • Change From Baseline in CD5-CD19+ Cell Counts at Screening, 3-Month Follow-up, and 6-Month Follow-up [ Time Frame: Screening, 3-Month Follow-up, and 6-Month Follow-up ] [ Designated as safety issue: No ]
    CD5-CD19+ cells were counted by flow cytometry. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus. Baseline CD5- CD19+ cell count value is the last pre-dose assessment values performed on cycle 1 Day 1. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

  • Number of Participants Who Were Negative or Positive for Minimal Residual Disease (MRD) and Achieved a Bone Marrow Biopsy Confirmed Complete Response (CR) at the 3-Month Follow-up [ Time Frame: From start of treatment until the 3-Month Follow-up visit ] [ Designated as safety issue: No ]
    MRD refers to small number of leukemic cells that remain in the participant during treatment or after treatment at the time the participant achieved a confirmed CR. MRD analysis was performed for the partcipants who were suspected of achieving a primary endpoint CR. Analysis of CD5+ CD19+ was performed on the bone marrow aspirate sample obtained no sooner than 2 months following the last dose of study treatment. MRD results were reported as negative or positive.

  • Number of Participants Who Recived no Transfusion or at Least One Transfusion During the Study [ Time Frame: From start of treatment until earliest date of disease progression or death (up to 3 years after the last dose of study treatment) ] [ Designated as safety issue: No ]
    Participants who received no transfusion and at least one transfusion during the study are presented. Participants who took any blood products are counted in this table.

  • Number of Participants With Autoimmune Hemolytic Anaemia (AIHA) Disease [ Time Frame: From first dose of study medication to 60 days after the last dose of study medication (if the event is considered as an AE), or up to 3 years after the last dose of study treatment or until the time of the next anti-CLL therapy, if considered a SAE ] [ Designated as safety issue: No ]
    AIHA is a disease where the body's immune system fails to recognize red blood cells as "self" and begins destroying these red blood cells. The number of participants diagnosed with AIHA are presented.

  • Number of Participants With the Indicated Grade 3 or Grade 4 Myelosuppression (Anemia, Neutropenia, and Thrombocytopenia), as Assessed by the Investigator [ Time Frame: From the first dose of study medication to 60 days after the last dose of study medication ] [ Designated as safety issue: No ]
    Participants with a Grade 3 or Grade 4 myelosuppression (anemia, neutropenia, and thrombocytopenia) are presented. Myelosuppression is defined as the decrease in the ability of the bone marrow to produce blood cells. AEs were graded according to NCI common terminology criteria for adverse events (CTCAE) grade, version 4.0 (1, mild; 2, moderate; 3, severe; 4, life-threatening/disabling; 5, death).

  • Number of Participants With the Indicated Grade 3 or Grade 4 Adverse Event of Infection [ Time Frame: From first dose of study medication to 60 days after the last dose of study medication (if the event is considered as an AE), or up to 3 years after the last dose of study treatment or until the time of the next anti-CLL therapy, if considered a SAE ] [ Designated as safety issue: No ]
    Participants with the indicated Grade 3 or Grade 4 adverse event of infection are presented. AEs were graded according to the NCI CTCAE grade, version 4.0 (1, mild; 2, moderate; 3, severe; 4, life-threatening/disabling; 5, death).

  • Number of Participants With the Indicated Constitutional or B-symptoms [ Time Frame: Screening (SCR), Cycle 1 Day 1 (C1D1), Cycle 2 Day 1 (C2D1) , Cycle 3 Day 1 (C3D1), Cycle 4 Day 1 (C4D1), Cycle 5 Day 1 (C5D1), Cycle 6 Day 1 (C6D1), 3-Month Follow-up (F/U), 6-Month F/U and 9-Month F/U ] [ Designated as safety issue: No ]
    Participants with the indicated constitutional or B-symptoms (night sweats, weight loss, fever or extreme fatigue) were presented for SCR, C1D1, C2D1, C3D1, C4D1, C5D1, C6D1, 3-Month F/U, 6-Month F/U and 9-Month F/U.

  • Number of Participants With the Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) [ Time Frame: BL, Cycle 1 Day 1 (C1D1), Cycle 2 Day 1 (C2D1) , Cycle 3 Day 1 (C3D1), Cycle 4 Day 1 (C4D1), Cycle 5 Day 1 (C5D1), Cycle 6 Day 1 (C6D1), 3-Month F/U, 6-Month F/U and 9-Month F/U and last assessment (LA) at or prior to study treatment discontinuation ] [ Designated as safety issue: No ]
    The ECOG performance status scales and criteria are used by doctors and researchers to assess how a participant's disease is progressing, assess how the disease affects the daily living abilities of the participant, and determine appropriate treatment and prognosis. Grade 0, fully active, able to carry on all pre-disease performance without restriction. Grade 1, restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. Grade 2, ambulatory and capable of all selfcare, but unable to carry out any work activities; up and about more than 50% of waking hours. Grade 3, capable of only limited selfcare; confined to bed or chair more than 50% of waking hours. Grade 4, completely disabled; cannot carry on any selfcare; totally confined to bed or chair. Grade 5, dead.

  • Number of Participants With Confirmed Positive Response for Human Anti-human Antibodies (HAHA) at the Indicated Time Points [ Time Frame: Cycle 1 Day 1 (C1D1), Cycle 6 Day 1 (C6D1), 6-Month Follow-up (F/U), and any post-dose time point ] [ Designated as safety issue: No ]
    The presence of HAHA in human serum was determined using a validated electrochemiluminescent assay in a multi-tier assay format. All samples were first assessed in a screening (SCR) assay, and the potential positive (Pos) samples were further tested in the confirmation (CNF) assays. Confirmed positives were reported as HAHA positive and titer was determined for each positive sample. The drug tolerance of the HAHA assay is 200 microgram/milliliter (µg/mL); thus, samples that tested negative in the assay and had ofatumumab concentrations no more than 200 µg/mL were considered as conclusive negative (C Neg) results.

  • Mean Maximum Decrease in Sum of the Product of the Diameter (SPD) From Baseline in Participants With Lymphadenopathy at Baseline [ Time Frame: Baseline, Cycle 2 Day 1 (C2D1), Cycle 3 Day 1 (C3D1), Cycle 4 Day 1 (C4D1), Cycle 5 Day 1 (C5D1), Cycle 6 Day 1 (C6D1), 3-Month Follow-Up (F/U), 6-Month F/U and 9-Month F/U ] [ Designated as safety issue: No ]
    Lymph nodes were evaluated by physical examination which involved recording the diameter in two planes (sum of the product of the diameter [SPD]) of the largest palpable node in each of the following sites: cervical, axillary, supraclavicular, inguinal and femoral. Lymphadenopathy is defined as lymph nodes with the largest diameter greater than 1.5 centimeters. The maximum reduction in SPD from Baseline at C2D1, C3D1, C4D1, C5D1, C6D1, 3-Month F/U, 6-Month F/U and 9-Month F/U are provided.

  • Number of Participants With the Indicated Reduction in Organomegaly (Spleen and Liver) [ Time Frame: Screening (Scr), Cycle 2 Day 1 (C2D1), Cycle 3 Day 1 (C3D1), Cycle 4 Day 1 (C4D1), Cycle 5 Day 1 (C5D1), Cycle 6 Day 1 (C6D1), 3-Month Follow-Up (F/U), 6-Month F/U and 9-Month F/U ] [ Designated as safety issue: No ]
    Organomegaly is the abnormal enlargement of organs. Physical examination of the liver (L) and spleen (S) were done at Scr, C1D1, C2D1, C3D1, C4D1, C5D1, C6D1, 3-Month F/U, 6-Month F/U and 9-Month F/U. The result of the physical examination of the liver (L) and spleen (S) was presented as normal (NOR), enlarged (EL) and not assessed (NOA).

  • Number of Participants With the Indicated Cytogenetics Testing at Baseline Who Also Had a Clinical Response After Last Dose of Study Treatment [ Time Frame: From the start of study treatment until earliest date of disease progression or death (up to up to 3 months following last dose of study treatment) ] [ Designated as safety issue: No ]
    Cytogenetics refers to the study of numerical and structural chromosomal abnormalities. Cytogenetics (analyzed by fluorescent in situ hybridization [FISH]) of 17p deletion, 11q deletion, 17p or 11q deletions, 6q- or +12q or 13q- deletions, and no aberration at Baseline were summarized by clinical responses after the last dose of study treatment. Clinical responses included complete remission (CR), nodular partial remission (nPR), complete response with incomplete bone marrow Recovery (CRi), partial remission (PR), disease progression (PD), and stable disease (SD). The participants with a PR, CRi, PR or nPR are called responders and the participants with SD and PD are called non-responders.

  • Number of Participants With the Indicated Beta 2 Microglobulin (B2M) at Baseline Who Also Had a Clinical Response After the Last Dose of Study Treatment [ Time Frame: From the start of study treatment until earliest date of disease progression or death (up to up to 3 months following last dose of study treatment) ] [ Designated as safety issue: No ]
    Participants with B2M concentration of <=4000 µg/L and >4000 µg/L at Baseline and who had clinical response after the last dose of study treatment were provided. Clinical responses included complete remission (CR), complete response with incomplete bone marrow Recovery (CRi), nodular partial remission (nPR), and partial remission (PR), disease progression (PD), and stable disease (SD). The participants with a PR, CRi, PR or nPR are called responders and the participants with SD and PD are called non-responders.

  • Number of Participants With the Indicated Immunoglobulin Heavy Chain Variable Region (IgVH) Testing at Baseline Who Also Had a Clinical Response After Last Dose of Study Treatment [ Time Frame: From the start of study treatment until earliest date of disease progression or death (up to up to 3 months following last dose of study treatment) ] [ Designated as safety issue: No ]
    Participants with IgVH mutation results as mutated and unmutated status and clinical response after last dose of study treatment were provided. Clinical responses included complete remission (CR), complete response with incomplete bone marrow recovery (CRi), nodular partial remission (nPR), partial remission (PR), disease progression (PD), and stable disease (SD). The participants with a PR, CRi, PR or nPR are called responders and the participants with SD and PD are called non-responders.

  • Number of Participants With Zeta-chain-associated Protein Kinase (ZAP) 70 Testing at Baseline Who Also Had a Clinical Response After Last Dose of Study Treatment [ Time Frame: From the start of study treatment until earliest date of disease progression or death (up to 3 months following last dose of study treatment) ] [ Designated as safety issue: No ]
    ZAP-70 is a protein normally expressed near the surface membrane of T cells and natural killer cells. ZAP-70 in B cells is used as a prognostic marker in identifying different forms of CLL. Participants with ZAP-70 testing results intermediate (Int), positive (Pos) and negative (Neg) at Baseline and who had a clinical response after last dose of study treatment are provided. Clinical responses included complete remission (CR), complete response with incomplete bone marrow recovery (CRi), nodular partial remission (nPR), partial remission (PR), disease progression (PD), and stable disease (SD). The participants with a PR, CRi, PR or nPR are called responders and the participants with SD and PD are called non-responders.

  • Number of Participants With an Adverse Event of Any Infusion Reactions (IR) or Serious Infusion Reactions (SIR) [ Time Frame: From the first dose of study medication to 60 days after the last dose of study medication (up to 24 hours after last dose of study treatment) ] [ Designated as safety issue: No ]
    An Infusion reaction is defined as events occurring after the beginning of an infusion of ofatumumab or within 24 hours following the end of an infusion of bendamustine.


Enrollment: 99
Study Start Date: March 2012
Estimated Study Completion Date: December 2015
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ofatumumab plus bendamustine
In this single arm, Phase II study, each patient who is willing to participate and is found eligible according to the inclusion and exclusion criteria will enter the treatment phase. Eligible subjects will be allocated to receive the following study treatments depending upon their previous CLL treatment status: Subjects with Untreated CLL: Up to 6 monthly intravenous infusions of Ofatumumab (Cycle 1: 300 mg Day 1 and 1000 mg Day 8; subsequent Cycles: 1000 mg at Day 1 every 28 days) in combination with up to 6 Cycles of intravenous infusions of bendamustine (90 mg/m2, Days 1 and 2; every 28 Days). Subjects with Relapsed CLL: Up to 6 monthly intravenous infusions of Ofatumumab (Cycle 1: 300 mg Day 1 and 1000 mg Day 8; subsequent Cycles: 1000 mg at Day 1 every 28 days) in combination with up to 6 Cycles of intravenous infusions of bendamustine (70 mg/m2, Days 1 and 2; every 28 Days).
Biological: Ofatumumab
Ofatumumab (ARZERRA™) is an immunoglobulin G1κ (IgG1κ) human monoclonal antibody that specifically recognises a distinct epitope encompassing both large and small extracellular loops on the human CD20 molecule expressed on B cells and binds to this site with high affinity with a dissociation half-life of approximately 3 hours. Ofatumumab induces more efficient complement-dependent cytotoxicity (CDC) mediated cell lysis in vitro, compared to rituximab, especially in low CD20 density cells.
Other Name: Arzerra
Drug: Bendamustine
Bendamustine is a cytostatic drug which structurally combines a purine-like benzamidazol nucleus and a bifunctional alkylating nitrogen mustard group.
Other Names:
  • Bendamustine hydrochloride
  • Levact
  • Ribomustin
  • Treanda

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • A diagnosis of CLL defined by a circulating B-lymphocyte count of greater than or equal to 5,000/uL at study entry or at any time in the past and flow cytometry confirmation of immunophenotype with CD5, CD19, CD20, CD23, CD79b, and surface Ig prior to first dose of study treatment.
  • Active disease and indication for treatment based on the IWCLL updated NCI-WG guidelines, defined by presence of at least any one of the following conditions: Evidence of progressive marrow failure as manifested by development or worsening of anaemia and/or thrombocytopenia; Massive (i.e. at least 6 cm below the left costal margin) or progressive or symptomatic splenomegaly; Massive nodes (i.e. at least 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy; Progressive lymphocytosis with an increase of more than 50% over a two-month period or a lymphocyte doubling time of less than 6 months.
  • A minimum of any one of the following disease-related symptoms must be present: a. Unintentional weight loss greater than or equal to 10% within the previous six months; b. Fevers greater than 100.5°F (38.0°C) for greater than or equal to 2 Weeks without evidence of infection; Or c. Night sweats for more than 1 month without evidence of infection.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
  • Age greater than or equal to 18 years.
  • Signed written informed consent from either the subject, or their legally acceptable representative if the subject is incapable of giving their own consent, prior to performing any study-specific tests or procedures.
  • Subjects enrolled into the previously untreated subject cohort must also meet all of the following criteria: No prior treatment for CLL (prior corticosteroid immunosuppression treatment for autoimmune hemolytic anaemia and idiopathic thrombocytopenic purpura (ITP) is permitted); Be considered inappropriate for fludarabine-based therapy for reasons that include, but are not limited to, advanced age or presence of co-morbidities.
  • Subjects enrolled into the relapsed subject cohort must also meet the following criteria: Relapsed CLL: defined as a subject who has received at least one prior CLL therapy and previously achieved a complete or partial remission/response lasting at least 6 months.

Exclusion Criteria:

  • Refractory CLL: defined as treatment failure (failure to achieve a CR or PR) or disease progression within 6 months of the last anti-CLL therapy.
  • Previous autologous or allogeneic stem cell transplantation.
  • Active autoimmune hemolytic anaemia (AIHA) and idiopathic thrombocytopenic purpura (ITP) requiring corticosteroid therapy greater than 25 mg prednisone (or equivalent) or chemotherapy.
  • Known transformation of CLL (e.g. Richter's).
  • Known central nervous system involvement by CLL. Screening laboratory values: Platelets less than 100 x 109/L (unless due to CLL involvement of the bone marrow). Neutrophils less than 1.5 x 109/L (unless due to CLL involvement of the bone marrow). Serum creatinine greater than 1.5 times the upper limit of normal (ULN); subjects with a serum creatinine greater than 1.5 x ULN will be eligible if the calculated creatinine clearance [Cockcroft, 1976] is greater than or equal to 30 mL/min. Total bilirubin greater than 1.5 times ULN (unless due to liver involvement by CLL or Gilbert's disease). Transaminases greater than 2.5 times ULN.
  • Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis, active Hepatitis C, and known Human Immunodeficiency Virus (HIV) disease. All HIV-positive subjects are excluded from this study, regardless of whether they have an Acquired Immunodeficiency Syndrome (AIDS) defining disease and/or are on antiviral therapy.
  • Other past or current malignancy (with the exception of basal cell carcinoma of the skin or in situ carcinoma of the cervix or breast) unless the tumour was successfully treated with curative intent at least 2 years prior to trial entry.*
  • Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months prior to first study treatment, congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities.*
  • History of significant cerebrovascular disease or event with significant symptoms or sequelae.*
  • Glucocorticoid use, unless given in doses less than or equal to 25mg/Day prednisone (or equivalent) for less than 7 Days for exacerbations other than CLL (e.g. asthma).*
  • Positive serology for Hepatitis B (HB) defined as a positive test for Hepatitis B surface antigen (HBsAg). In addition, if negative for HBsAg but Hepatitis B core antibody (HBcAb) positive, a Hepatitis B Virus (HBV) DNA test will be performed and if positive the subject will be excluded.
  • Known or suspected hypersensitivity to ofatumumab or bendamustine that in the opinion of the investigator is a contraindication to their participation in the present study.
  • Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 Weeks prior to first study treatment dose, whichever is longer, or participation in any other interventional clinical study.
  • Known or suspected inability to comply with the study protocol.
  • Lactating women, women with a positive pregnancy test at Visit 1 or women (of childbearing potential) as well as men with partners of childbearing potential, who are not willing to use adequate contraception from study start through one year following last ofatumumab dose. Adequate contraception is defined as abstinence, oral hormonal birth control, implants of levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, intrauterine device, and male partner sterilisation if male partner is sole partner for that subject. For females in the USA, the use of a double barrier method is also considered adequate (condom or occlusive cap plus spermicidal agent).

    • Subjects can participate in the study if in the opinion of the investigator it is thought not to affect the subject's safety, the conduct of the study or the interpretation of the data.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01520922

  Show 30 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01520922     History of Changes
Other Study ID Numbers: 115991
Study First Received: January 19, 2012
Results First Received: October 10, 2013
Last Updated: August 7, 2014
Health Authority: Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Germany: Federal Agency for Sera and Vaccines
United States: Food and Drug Administration
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Italy: Ethics Committee for Clinical Trials
Russia: Ministry of Health of the Russian Federation
Spain: Spanish Agency for Medicines and Health Products
Greece: National Drug Organisation
Czech Republic: State Institute for Drug Control

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bendamustine
Nitrogen Mustard Compounds
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 20, 2014