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Ofatumumab Added to Fludarabine-Cyclophosphamide vs Fludarabine-Cyclophosphamide Combination in Relapsed Subjects With Chronic Lymphocytic Leukemia

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ClinicalTrials.gov Identifier: NCT00824265
Recruitment Status : Completed
First Posted : January 16, 2009
Results First Posted : July 25, 2016
Last Update Posted : January 12, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The purpose of this study is to evaluate the safety and efficacy of ofatumumab added to fludarabine-cyclophosphamide in patients with relapsed Chronic Lymphocytic Leukemia (CLL).

Condition or disease Intervention/treatment Phase
Leukaemia, Lymphocytic, Chronic Drug: OFC Infusion Drug: FC infusion Phase 3

Detailed Description:

Fludarabine is currently approved for treatment of relapsed Chronic Lymphocytic Leukemia. Studies have shown that drugs in combination with fludarabine have shown more effectiveness than fludarabine alone. The addition of ofatumumab to fludarabine-cyclophosphamide combination offers potentially a more effective therapy, without additional toxicity.

The objective of this study is to determine the effect of ofatumumab added to fludarabine and cyclophosphamide in patients with Chronic Lymphocytic Leukemia who have responded previously to therapy but later develop progressive disease and require additional therapy.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 365 participants
Allocation: Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III, Open Label, Randomized Trial of Ofatumumab Added to Fludarabine-Cyclophosphamide vs. Fludarabine-Cyclophosphamide Combination in Subjects With Relapsed Chronic Lymphocytic Leukemia
Study Start Date : March 2009
Actual Primary Completion Date : December 2014
Actual Study Completion Date : October 25, 2017


Arm Intervention/treatment
Experimental: Ofatumumab, Fludarabine, Cyclophosphamide
Ofatumumab Cycle 1-Day 1 300mg, Cycle 1-Day 8 1000mg, then Cycles 2-6 Day 1 1000mg every 28 days, Fludarabine 25mg/m2 Days 1-3 every 28 days for 6 cycles, Cyclophosphamide 250 mg/m2 Days 1-3 every 28 days for 6 cycles
Drug: OFC Infusion
Ofatumumab Cycle 1-Day 1 300mg, Cycle 1-Day 8 1000mg, then Cycles 2-6 Day 1 1000mg every 28 days, Fludarabine 25mg/m2 Days 1-3 every 28 days for 6 cycles, Cyclophosphamide 250 mg/m2 Days 1-3 every 28 days for 6 cycles

Active Comparator: Fludarabine, Cyclophosphamide
Fludarabine 25mg/m2 Days 1-3 every 28 days for 6 cycles, Cyclophosphamide 250 mg/m2 Days 1-3 every 28 days for 6 cycles
Drug: FC infusion
Fludarabine 25mg/m2 Days 1-3 every 28 days for 6 cycles, Cyclophosphamide 250mg/m2 Days 1-3 every 28 days for 6 cycles




Primary Outcome Measures :
  1. Progression-free Survival (PFS), as Assessed by the Independent Review Committee (IRC) [ Time Frame: From randomization up to 5 years after last dose of study drug ]
    PFS is defined as the interval of time between the date of randomization and the earlier of the date of disease progression (progressive disease,PD) and the date of death due to any cause. PD requires at least one of the following: lymphadenopathy, appearance of any new lesion such as enlargerd lymph nodes (>1.5 cm) spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site; an increase by 50% or more in the previously noted enlargement of the liver or spleen, an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter, transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukaemia.


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: From randomization up to 5 years after last dose of study drug ]
    Overall survival is defined as the time from randomization to death due to any cause. Each participant was followed at the time when the last IRC-assessed PFS events occurred. Participants who had not died were censored at the date of last contact.

  2. Time to Response, as Assessed by the IRC [ Time Frame: From randomization up to 5 years after last dose of study drug ]
    Time to response is defined as the time from randomization to the first response. Complete Response/remission(CR) all the criteria at least 2 months after last treatment: no lymphadenopathy(Ly) > 1.5 cm/ hepatomegaly/spleenomegaly/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. Incomplete bone marrow recovery(CRi): CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. Partial Remission/response(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. Nodular PR(nPR): persistent nodules BM.

  3. Duration of Response (DOR), as Assessed by the IRC [ Time Frame: From time of initial response to disease progression or death, whichever came first (up to 5 years after the last dose of study drug) ]
    DOR is defined as the time from the initial response (CR, CRi, nPR, or PR) to the first documented sign of PD or death due to any cause. PD requires at least one of the following: lymphadenopathy, appearance of any new lesion such as enlargerd lymph nodes (>1.5 cm) spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site; an increase by 50% or more in the previously noted enlargement of the liver or spleen, an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter, transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukaemia.

  4. Time to Progression, as Assessed by the IRC [ Time Frame: From randomization up to 5 years after the last dose of study drug ]
    Time to progression is defined as the time from the date of randomization to PD. PD requires at least one of the following: lymphadenopathy, appearance of any new lesion such as enlargerd lymph nodes (>1.5 cm) spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site; an increase by 50% or more in the previously noted enlargement of the liver or spleen, an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter, transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukaemia.

  5. Time to Next Therapy [ Time Frame: From the start of study drug until the start of the next anti-CLL therapy (up to 5 years after the last dose of study drug) ]
    Time to next therapy is defined as the time from randomization until the start of the next-line of treatment.

  6. Number of Participants With Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status [ Time Frame: Cycle 2 Day1, Cycle 3 Day1, Cycle 4 Day1, Cycle 5 Day1, Cycle 6 Day1, follow up (FU) at 1Month (M) after study drug therapy, then every 3 month up to 5 year (up to 60 months) ]
    The ECOG performance status scales and criteria are used by doctors and researchers to assess how a participant's disease is progressing, how the disease affects the daily living, and determines appropriate treatment and prognosis. ECOG performance status are measured at Cycle 2 Day1, Cycle 3 Day1, Cycle 4 Day1, Cycle 5 Day1 and Cycle 6 Day1. During follow period, 1 M after study drug therapy, then every 3 month up to 5 year (up to 60 months). Improvement is defined as a decrease from baseline by at least one step on the ECOG performance status scale (yes/no).

  7. Number of Participants With no B-Symptoms or at Least One B-symptoms Over the Time [ Time Frame: Screening, Cycle1 Day 1, Cycle 2 Day1, Cycle 3 Day1, Cycle 4 Day1, Cycle 5 Day1, Cycle 6 Day 1 and During at 1M after study drug therapy, then every 3 M up to 5 year (up to 60 months) ]
    Participants with no B-symptoms (B-Sy) (no night sweat, no weight loss, no fever and no extreme fatigue) and at least one indicated B-sy(night sweats, weight loss, fever or extreme fatigue) were presented at Screening, Cycle 1 Day 1, Cycle 2 Day1, Cycle 3 Day1, Cycle 4 Day1, Cycle 5 Day1, Cycle 6 Day 1 and during follow up period at 1 M after study drug therapy, then every 3 M up to 5 year (up to 60 months).

  8. Percentage of Participants With the Best Overall Response (OR), as Assessed by the IRC [ Time Frame: From randomization up to 5 years after last dose of study drug ]
    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]). CR (all the criteria at least 2 months after last treatment): no lymphadenopathy (Ly) > 1.5 cm/ 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. nPR: persistent nodules BM.

  9. Percentage of Participants With the Best OR, as Assessed by the Investigator [ Time Frame: From randomization up to 5 years after last dose of study drug ]
    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]). CR (all the criteria at least 2 months after last treatment): no lymphadenopathy (Ly) > 1.5 cm/ 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. nPR: persistent nodules BM.

  10. Number of Participants Who Were Negative for Minimal Residual Disease (MRD) Assessed by IRC [ Time Frame: From randomization up to 5 years after last dose of study drug ]
    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 participants who were suspected of achieving a primary endpoint CR. MDR was performed by flow cytometry on a bone marrow or peripheral blood sample taken at least 2 months after final treatment. MRD negative was defined as less than one CLL cell per 10000 leukocytes.

  11. Number of Participants Who Were Negative for MRD Assessed by Investigator [ Time Frame: From randomization up to 5 years after last dose of study drug ]
    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 participants who were suspected of achieving a primary endpoint CR. MDR was performed by flow cytometry on a bone marrow or peripheral blood sample taken at least 2 months after final treatment. MRD negative was defined as less than one CLL cell per 10000 leukocytes.

  12. 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 (for an AE), or up to 5 years after the last dose of study drug or until the time of the next anti-CLL therapy (for SAE) ]
    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.

  13. Number of Participants With a Human Anti-human Antibody (HAHA) Positive Result at Indicated Time Points [ Time Frame: From start of study drug until 60 days after the last dose of study medication ]
    Serum samples for analysis of HAHA were collected at Baseline (Screening), after 3 cycles were compelted, after 1 M and 6 M post last dose. All samples were first tested in a screening step; positive samples from the screening were further evaluated in a confirmation test. The confirmed positive samples were reported as HAHA-positive.

  14. Number of Participants With Autoimmune Hemolytic Anaemia (AIHA) [ Time Frame: From first dose of study medication to 60 days after the last dose of study medication (for an AE), or up to 5 years after the last dose of study drug or until the time of the next anti-CLL therapy (for SAE) ]
    AIHA is a condition 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 experienced AIHA are presented.

  15. Number of Participants With Drug Related AEs and SAEs of Maximum Severity of Grade 3 or Higher [ Time Frame: From first dose of study medication to 60 days after the last dose of study medication (for an AE), or up to 5 years after the last dose of study drug or until the time of the next anti-CLL therapy (for SAE) ]
    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. Maximum severity grades were evaluated according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 3.0 (1, mild; 2, moderate; 3, severe; 4, life-threatening/disabling; 5, death).

  16. Number of Participants With at Least One Grade 3/Grade 4 Myelosuppression (Anemia, Neutropenia, and Thrombocytopenia) [ Time Frame: From first dose of study medication to 60 days after the last dose of study medication (for an AE), or up to 5 years after the last dose of study drug or until the time of the next anti-CLL therapy (for SAE) ]
    Participants with at least one 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 3.0 (1, mild; 2, moderate; 3, severe; 4, life-threatening/disabling; 5, death).

  17. Number of Participants Who Received no Transfusion or at Least One Transfusion During the Study [ Time Frame: From randomization up to 5 years after last dose of study drug ]
    Participants who received no transfusion and at least one transfusion during the study are presented. Participants who took any blood products or blood supportive care product are included.

  18. Mean Level of Immunoglobulin (Ig) Antibodies IgA, IgG, and IgM [ Time Frame: Baseline, 1M and 6M follow up ]
    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. Blood samples were collected from each participant and IgA, IgG, and IgM were measured at Baseline, and 1M and 6M after last dose during follow up period.

  19. Change From Baseline in Cluster of Differentiation (CD) Cell Counts, CD5+ and CD19+ [ Time Frame: Screening, Cycle 1 Day1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and after last dose at 1 M and then every three months up to 45 M during Follow-up Period ]
    CD5+ and CD19+ cells were counted by flow cytometry at Screening (Baseline) on Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 during the treatment period and after last dose of study drug at 1 M and then every three month follow up up to 45 M. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus. Baseline is defined as the assessment closest to but prior to first dose (e.g. day 1 if available, otherwise, screening). Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

  20. Change From Baseline in Cell Counts, CD5- CD19+ [ Time Frame: Screening, Cycle 1 Day1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and after last dose at 1 M and then every three month up to 45 M during Follow-up Period ]
    CD5- CD19+ cells were counted by flow cytometry at Screening (baseline) at Cycle 1 Day1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 during treatment period and after last dose of study drug at 1 M and then every three month up to 45 M during follow up period. Flow cytometry is a technique for counting and examining microscopic particles with an electronic detection apparatus. Baseline is defined as the assessment closest to but prior to first dose (e.g. Day 1 if available otherwise screening). Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

  21. Prognostic and Biological Markers Correlating With Clinical Response [ Time Frame: From randomization up to 5 years after last dose of study drug ]
    Blood samples were collected for the assessment of the following prognostic markers at BL: immunoglobulin heavy chain variable region(IgVH) homology; Zeta-Chain-Associated Protein Kinase 70(ZAP70), VH3-21 usage; Cytogenetics (by fluorescent in situ hybridization [FISH]); beta 2 microglobulin. Cox-regression model was used to explore the relationship between progression-free survival and the following explanatory variables: treatment group, cytogenetics (analyzed by FISH included 6q-,11q-, +12q, 17p-, 13q-) , ZAP-70 (positive, negative or intermediate), VH3-21 usage (Yes and No), IgVH homology (>98%, 97%-98% and <97%), beta 2 microglobulin (>3500 microgram per liter [µg/L] and <=3500 µg/L). For each covariate, a hazard ratio <1 indicates a lower risk on the first effect tested compared with the other effects tested. Cytogenetics Group (based on >=20%)=cytogenetics (CY G).

  22. Changes in Patient Reported Outcome (PRO) Measures and Scores for European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Chronic Lymphocytic Leukaemia 16 Item Module (EORTC QLQ-CLL 16) [ Time Frame: Screening, Cycle 3 Day 1, and 1 M and every 3 month post last dose up to 24 month. ]
    The EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of health-related quality of life (HRQoL) important in CLL. There are 4 multi-item scales - fatigue (2 items), treatment side effects ([TSE], 4 items), disease symptoms (disease effects scale [DES], 4 items), and infection scale [IS] (4 items) - and single item scales (social activities [Social Problems (SP) Scale] and future health worries[Future Health (FH) Scale].). These are measured on a four point scale where 1 = not at all and 4 = very much. These scores are transformed to give a rating from 0 - 100, where 0 =no symptoms or problems and 100 = a severe symptoms or problems. EORTC QLQ-CLL16 was assessed at Screening; Cycle 4 Day 1 and during follow-up 1 M and every 3 M up to 24 months. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value was obtained at randomization.

  23. Change From Baseline in Patient Reported Outcome (PRO) as Assessed by EuroQoL Five-Dimension (EQ-5D) Score at Indicated Visit [ Time Frame: Screening, Cycle 3 Day 1, and 1 M and every 3 month post last dose up to 24 month. ]
    EQ-5D is comprised of a 5-item health status measure and a visual analogue scale (VAS) and is used to generate two scores: the utility score and the thermometer score. The utility score measures mobility, self-care, usual activities, pain, discomfort, and anxiety/depression. Responses to each of the 5 health states are measured on a 3-point scale (level 1 = no problem; level 2 = some or moderate problem(s) and level 3 = unable, or extreme problems). Responses are typically converted into health utilities or valuations on a scale ranging from 0 (death) to 1 (perfect health). The thermometer score ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A Negative health status describes health state worse than death.Baseline is the most recent, non-missing value prior to or on the first study drug dose date.

  24. Change From Baseline in the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Score [ Time Frame: Screening, Cycle 3 Day 1, and 1 M and every 3 month post last dose up to 24 month. ]
    EORTC QLQ-C30, a self-reported, cancer-specific instrument assessing 15 domains: physical, role, emotional, cognitive and social functioning, pain,fatigue, nausea and vomiting, insomnia, loss of appetite, constipation, diarrhea, and dyspnea, financial difficulties and a global health status/quality of life (QOF). Functional and symptoms scales were measured on four point Likert scale where 1 = not at all and 4 = very much. Pat. assessed at Screening; Cycle 4 Day 1 and during follow-up 1 M and every 3 M up to 24 months. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline is the most recent, non-missing value prior to or on the first study treatment dose date. Clinically meaningful changes or minimally important differences (MIDs)have been previously established for the EORTC QLQ C30, and categorized as 'small' if the mean change in scores is 5-10 points, 'moderate' if 10-20 points, and 'large' if >20points.

  25. Mean of Health Change Questionnaire (HCQ) [ Time Frame: Screening, Cycle 3 Day 1, and 1 M and every 3 month post last dose up to 24 month. ]
    The HCQ consists of a single question in which the participant is asked if he/she has experienced any change in his/her health overall since beginning the study. For HCQ, values from 1 to 9 were assigned to the 9 responses in the HCQ questionnaire, ranging from 1 for 'my health is a great deal better' to 9 for 'my health is a great deal worse' since the beginning of the study. Lower scores represent better conditions.

  26. Mean Area Under the Time-concentration Curve (AUC) Curve Over the Dosing Interval (AUC[0-tau]) of Ofatumumab [ Time Frame: Cycle 1 Week 1, Cycle 1 Week 2, Cycles 2,3,4,5,6 ]
    Area under the time-concentration curve (AUC) over the dosing interval (AUC[0-tau]) was evaluated. Blood samples were collected from participants who received ofatumumab plus fludarabine and cyclophosphamide predose and 0.5 h after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, predose samples were collected prior to ofatumumab administration at Cycles 2, 3, 5, and 6 (Days 29, 57, 113, and 141).

  27. Maximum Concentration (Cmax) and Observed Drug Concentration Prior to the Next Dose (Ctrough) of Ofatumumab [ Time Frame: Cycle 1 Week 1, Cycle 1 Week 2, Cycles 2,3,4,5 ]
    Blood samples were collected to assess the plasma concentration of ofatumumab.Cmax and Ctrough were determined. Blood samples were collected from participants who received ofatumumab plus fludarabine and cyclophosphamide predose and 0.5 h after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4 (Days 1, 8, and 85). In addition, predose samples were collected prior to ofatumumab administration at Cycles 2, 3, 5, and 6 (Days 29, 57, 113, and 141).

  28. Time of Occurrence of Cmax (Tmax) of Ofatumumab [ Time Frame: Cycle 1 Week 1, Cycle 1 Week 2, Cycle 4 ]
    Blood samples were collected from participants who received ofatumumab plus fludarabine and cyclophosphamide predose and 0.5 h after the end of the ofatumumab infusion at treatment Cycle 1 and Cycle 4.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • confirmed and active CLL requiring treatment
  • at least one previous treatment for CLL and having achieved a complete or partial remission/response but after a period of 6 or more months, shows evidence of disease progression
  • fully active at a minimum or fully capable of selfcare and up and about more than 50% of waking hours
  • age 18yrs or older
  • signed written informed consent

Exclusion Criteria:

  • diagnosis of refractory CLL (failure to achieve a complete or partial remission/response or disease progression within 6 months of last anti-CLL treatment
  • abnormal/inadequate blood values, liver and kidney function
  • certain heart problems, serious significant diseases, AIHA, other current cancers or within the last 5 years
  • active or chronic infections
  • use of drugs to suppress allergic or inflammatory responses (glucocorticoids)
  • CLL transformation
  • CLL central nervous system involvement
  • current participation in other clinical study
  • inability to comply with the protocol activities
  • lactating or pregnant women or female patients of child-bearing potential (or male patients with such partners) not willing to use adequate contraception

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00824265


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Locations
United States, Florida
Novartis Investigative Site
Boca Raton, Florida, United States, 33486
United States, Illinois
Novartis Investigative Site
Chicago, Illinois, United States, 60612-3833
United States, Maryland
Novartis Investigative Site
Clinton, Maryland, United States, 20735
United States, Missouri
Novartis Investigative Site
Kansas City, Missouri, United States, 64128
Novartis Investigative Site
Saint Louis, Missouri, United States, 63110
United States, Tennessee
Novartis Investigative Site
Memphis, Tennessee, United States, 38120
Brazil
Novartis Investigative Site
Brasilia, Goiás, Brazil, 70390-150
Novartis Investigative Site
Porto Alegre, Rio De Janeiro, Brazil, 91350-200
Novartis Investigative Site
Porto Alegre, Rio Grande Do Sul, Brazil, 90610000
Novartis Investigative Site
Rio de Janeiro, Brazil, 20211-030
Novartis Investigative Site
Rio de Janeiro, Brazil, 20230 -130
Novartis Investigative Site
Rio de Janeiro, Brazil, 21941-913
Novartis Investigative Site
São Paulo, Brazil, 03102-002
Novartis Investigative Site
São Paulo, Brazil, 05403-000
Bulgaria
Novartis Investigative Site
Pleven, Bulgaria, 5800
Novartis Investigative Site
Plovdiv, Bulgaria, 4000
Novartis Investigative Site
Sofia, Bulgaria, 1233
Novartis Investigative Site
Sofia, Bulgaria, 1407
Novartis Investigative Site
Sofia, Bulgaria, 1606
Novartis Investigative Site
Sofia, Bulgaria
Novartis Investigative Site
Varna, Bulgaria, 9010
Canada, British Columbia
Novartis Investigative Site
New Westminster, British Columbia, Canada, V3L 3W4
Canada, Ontario
Novartis Investigative Site
Kitchener, Ontario, Canada, N2G 1G3
Novartis Investigative Site
Newmarket, Ontario, Canada, L3Y 2P9
Novartis Investigative Site
Ottawa, Ontario, Canada, K1H 8L6
Canada, Quebec
Novartis Investigative Site
Greenfield Park, Quebec, Canada, J4V 2H1
Novartis Investigative Site
Montreal, Quebec, Canada, H1T 2M4
Novartis Investigative Site
Sherbrooke, Quebec, Canada, J1H 5N4
Canada, Saskatchewan
Novartis Investigative Site
Saskatoon, Saskatchewan, Canada, S7N 4H4
Germany
Novartis Investigative Site
Karlsruhe, Baden-Wuerttemberg, Germany, 76137
Novartis Investigative Site
Stuttgart, Baden-Wuerttemberg, Germany, 70190
Novartis Investigative Site
Stuttgart, Baden-Wuerttemberg, Germany, 70376
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Villingen-Schwenningen, Baden-Wuerttemberg, Germany, 78052
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Muenchen, Bayern, Germany, 81241
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Frankfurt, Hessen, Germany, 65929
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Kassel, Hessen, Germany, 34119
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Hannover, Niedersachsen, Germany, 30625
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Lehrte, Niedersachsen, Germany, 31275
Novartis Investigative Site
Essen, Nordrhein-Westfalen, Germany, 45122
Novartis Investigative Site
Moenchengladbach-Rheydt, Nordrhein-Westfalen, Germany, 41239
Novartis Investigative Site
Muenster, Nordrhein-Westfalen, Germany, 48149
Novartis Investigative Site
Saarbruecken, Saarland, Germany, 66113
Novartis Investigative Site
Dresden, Sachsen, Germany, 01307
Novartis Investigative Site
Luebeck, Schleswig-Holstein, Germany, 23562
Novartis Investigative Site
Hamburg, Germany, 22767
Greece
Novartis Investigative Site
Athens,, Greece, 11 527
Novartis Investigative Site
Athens, Greece, 11527
Novartis Investigative Site
Thessaloniki, Greece, 564 29
Novartis Investigative Site
Thessaloniki, Greece, 57010
India
Novartis Investigative Site
Bangalore, India, 560029
Novartis Investigative Site
Mumbai, India, 400012
Novartis Investigative Site
Mumbai, India, 400014
Novartis Investigative Site
New Delhi, India, 110029
Novartis Investigative Site
Pune, India, 411001
Novartis Investigative Site
Vadodara, India, 390007
Italy
Novartis Investigative Site
Potenza, Basilicata, Italy, 85100
Novartis Investigative Site
Albano Laziale (Roma), Lazio, Italy, 00041
Novartis Investigative Site
Roma, Lazio, Italy, 00161
Novartis Investigative Site
Genova, Liguria, Italy, 16132
Novartis Investigative Site
Pavia, Lombardia, Italy, 27100
Novartis Investigative Site
Ascoli Piceno, Marche, Italy, 63100
Novartis Investigative Site
Alessandria, Piemonte, Italy, 15100
Novartis Investigative Site
Novara, Piemonte, Italy, 28100
Novartis Investigative Site
Catania, Sicilia, Italy, 95124
Novartis Investigative Site
Palermo, Sicilia, Italy, 90146
Mexico
Novartis Investigative Site
Guadalajara, Jalisco, Mexico, 44280
Novartis Investigative Site
Monterrey, Nuevo León, Mexico, 64460
Novartis Investigative Site
Monterrey, Nuevo León, Mexico, 64710
Novartis Investigative Site
Mexico City, Mexico, CP 14080
Netherlands
Novartis Investigative Site
Amersfoort, Netherlands, 3818 ES
Novartis Investigative Site
Den Haag, Netherlands, 2545 CH
Novartis Investigative Site
Nijmegen, Netherlands, 6525 GA
Novartis Investigative Site
Rotterdam, Netherlands, 3015 CE
Novartis Investigative Site
Rotterdam, Netherlands, 3075 EA
Poland
Novartis Investigative Site
Bialystok, Poland, 15-276
Novartis Investigative Site
Chorzow, Poland, 41-500
Novartis Investigative Site
Krakow, Poland, 31-501
Novartis Investigative Site
Lodz, Poland, 93-510
Novartis Investigative Site
Opole, Poland, 45-372
Novartis Investigative Site
Slupsk, Poland, 76-200
Novartis Investigative Site
Szczecin, Poland, 71-242
Novartis Investigative Site
Warszawa, Poland, 02-507
Novartis Investigative Site
Warszawa, Poland, 02-776
Novartis Investigative Site
Warszawa, Poland, 02-781
Novartis Investigative Site
Wroclaw, Poland, 50-367
Romania
Novartis Investigative Site
Bucharest, Romania, 022328
Novartis Investigative Site
Bucharest, Romania, 050098
Novartis Investigative Site
Iasi, Romania, 700483
Novartis Investigative Site
Timisoara, Romania, 300329
Russian Federation
Novartis Investigative Site
Kazan, Russian Federation, 420029
Novartis Investigative Site
Moscow, Russian Federation, 115478
Novartis Investigative Site
Moscow, Russian Federation, 125101
Novartis Investigative Site
Moscow, Russian Federation, 125167
Novartis Investigative Site
Novosibirsk, Russian Federation, 630087
Novartis Investigative Site
St'Petersburg, Russian Federation, 191024
Novartis Investigative Site
St. Petersburg, Russian Federation, 197 089
Spain
Novartis Investigative Site
Badalona/Barcelona, Spain, 08916
Novartis Investigative Site
Barcelona, Spain, 08003
Novartis Investigative Site
Barcelona, Spain, 08025
Novartis Investigative Site
Madrid, Spain, 28006
Novartis Investigative Site
Madrid, Spain, 28040
Novartis Investigative Site
Madrid, Spain, 28046
Novartis Investigative Site
Salamanca, Spain, 37007
Novartis Investigative Site
Sevilla, Spain, 41014
Taiwan
Novartis Investigative Site
Taichung, Taiwan, 404
Novartis Investigative Site
Tainan, Taiwan, 704
Novartis Investigative Site
Taipei, Taiwan, 100
Novartis Investigative Site
Taipei, Taiwan, 112
Thailand
Novartis Investigative Site
Bangkok, Thailand, 10330
Novartis Investigative Site
Bangkok, Thailand, 10400
Novartis Investigative Site
Bangkok, Thailand, 10700
Ukraine
Novartis Investigative Site
Cherkasy, Ukraine, 18009
Novartis Investigative Site
Dnipropetrovsk, Ukraine, 49102
Novartis Investigative Site
Kharkiv, Ukraine, 61070
Novartis Investigative Site
Khmelnytskyi, Ukraine, 29000
Novartis Investigative Site
Kyiv, Ukraine, 03022
Novartis Investigative Site
Kyiv, Ukraine, 04112
Novartis Investigative Site
Lviv, Ukraine, 79044
Novartis Investigative Site
Makiivka, Ukraine, 86132
Novartis Investigative Site
Simferopil, Ukraine, 95023
Novartis Investigative Site
Vinnitsa, Ukraine, 21018
Novartis Investigative Site
Zhytomyr, Ukraine, 10002
United Kingdom
Novartis Investigative Site
Birmingham, United Kingdom, B9 5SS
Novartis Investigative Site
Bradford, United Kingdom, BD9 6RJ
Novartis Investigative Site
Burton on Trent, United Kingdom, DE13 0RB
Novartis Investigative Site
Carshalton, United Kingdom, SM5 1AA
Novartis Investigative Site
Cornwall, United Kingdom, TR1 3LJ
Novartis Investigative Site
Cottingham, United Kingdom, HU16 5JQ
Novartis Investigative Site
Dudley, United Kingdom, DY1 2HQ
Novartis Investigative Site
Glasgow, United Kingdom, G12 OYN
Novartis Investigative Site
Leicester, United Kingdom, LE1 5WW
Novartis Investigative Site
Manchester, United Kingdom, M13 9WL
Novartis Investigative Site
Salford, United Kingdom, M6 8HD
Novartis Investigative Site
Swindon, United Kingdom, SN3 6BB
Novartis Investigative Site
Uxbridge, United Kingdom, UB8 3NN
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00824265     History of Changes
Other Study ID Numbers: 110913
First Posted: January 16, 2009    Key Record Dates
Results First Posted: July 25, 2016
Last Update Posted: January 12, 2018
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Relapsed
Oncology
Safety
Chronic Lymphocytic Leukemia
Ofatumumab
Efficacy

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Ofatumumab
Antibodies, Monoclonal
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents