Ofatumumab With High Dose Methylprednisone Followed by Ofatumumab and Alemtuzumab in 17p CLL

Sponsor
Dana-Farber Cancer Institute (Other)
Overall Status
Terminated
CT.gov ID
NCT01465334
Collaborator
National Comprehensive Cancer Network (Other), GlaxoSmithKline (Industry)
30
Enrollment
2
Locations
2
Arms
61
Duration (Months)
15
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main purpose of this study is to examine how two separate groups of 17p deletion Chronic lymphocytic leukemia (CLL) participants respond to sequential treatment with this particular combination of drugs. The two groups are those participants who have previously received treatment for their CLL and those who have not yet received any treatment. The combination of drugs is Ofatumumab and High-Dose Methylprednisolone (HDMP) first followed by Ofatumumab and Alemtuzumab. All three drugs are FDA approved and have known activity in treating 17p CLL. We hope that by combining these drugs together in this study, they will have more benefit than each one alone and that the subjects' CLL will be significantly impacted.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Detailed Description

Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy.

Part A: Ofatumumab + HDMP 2-4 cycles Part B: Ofatumumab + Alemtuzumab 1-6 cycles Part C:

Maintenance with Ofatumumab + Alemtuzumab up to 2 years

Between days 15-22 of Cycle 2 of Part A, participants are restaged. Participants who achieve nodal complete response discontinue Part A therapy and undergo minimal residual disease (MRD) assessment to guide the decision whether to go to Part B or Part C. The participants with persistent disease after 2 cycles of Part A therapy receive 2 more cycles of Part A therapy and then undergo another restaging as well as MRD assessment. At restaging, participants with minimal disease are eligible for Part C or allogeneic stem cell transplant (SCT) off protocol. The remaining participants receive Part B therapy. On Part B, restaging occurs at weeks 12 and 18. If MRD negative complete response (CR) status is achieved then therapy is discontinued and the primary endpoint evaluation occurs 2 months later. Otherwise with persistent disease Part B therapy continues up to 24 weeks and the primary endpoint evaluation occurs after Part B therapy is completed. Participants who achieve clinical complete response may receive Part C therapy or be observed while waiting SCT.

Study Design

Study Type:
Interventional
Actual Enrollment :
30 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Study of Ofatumumab-High Dose Methylprednisolone Followed by Ofatumumab-Alemtuzumab in 17p Deletion CLL
Study Start Date :
Dec 1, 2011
Actual Primary Completion Date :
Nov 1, 2014
Actual Study Completion Date :
Jan 1, 2017

Arms and Interventions

ArmIntervention/Treatment
Experimental: Treatment Naive

Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28

Drug: Ofatumumab
Other Names:
  • GSK 1841157
  • Drug: High-Dose Methylprednisolone
    Other Names:
  • HDMP
  • Drug: Alemtuzumab
    Other Names:
  • Campath-1H
  • Experimental: Relapsed/Refractory

    Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28

    Drug: Ofatumumab
    Other Names:
  • GSK 1841157
  • Drug: High-Dose Methylprednisolone
    Other Names:
  • HDMP
  • Drug: Alemtuzumab
    Other Names:
  • Campath-1H
  • Outcome Measures

    Primary Outcome Measures

    1. Induction Overall Response Rate (ORR) [Disease was evaluated after weeks 8 and 16 of Part A and at 12, 18 and 24 weeks during part B.]

      Induction ORR is the percentage of participants achieving a minimum of partial response (PR) over induction treatment based on International Workshop on Chronic Lymphocytic Leukemia (IW-CLL) criteria (Hallek, et al 2008). There are numerous diagnostic tests used for response evaluation including potentially CBC and differential count, marrow aspirate and biopsy, ultrasound of the abdomen, CT scans (chest, pelvis, abdomen) and physical examination. PR is a 50% or greater decrease of measured size of lymphadenopathy, hepatomegaly, splenomegaly as well as blood lymphocytes (over baseline), marrow infiltrate or B-lymphoid nodules and a 50% or greater increase from baseline in platelet count (or level >100,000/micro liter), hemoglobin (or level >11 grams/deciliter), neutrophils (or level >1500/microliter).

    Secondary Outcome Measures

    1. Number of Participants Achieving Induction Complete Response (CR) [Disease was evaluated after weeks 8 and 16 of Part A and at 12, 18 and 24 weeks during part B.]

      CR over induction treatment was based on International Workshop on Chronic Lymphocytic Leukemia (IW-CLL) criteria (Hallek, et al 2008). There are numerous diagnostic tests used for response evaluation including potentially CBC and differential count, marrow aspirate and biopsy, ultrasound of the abdomen, CT scans (chest, pelvis, abdomen) and physical examination. CR is absence of significant lymphadenopathy (nodes<1.5 centimeters in long axis diameter), hepatomegaly, splenomegaly as well as blood lymphocytes<4000/microliter, normocellular for age marrow with <30% lymphocytes, no B-lymphoid nodules and platelet>100,000/micro liter, hemoglobin>11 grams/deciliter, neutrophils>1500/microliter.

    2. Overall Objective Response Rate (ORR) [Disease was evaluated after weeks 8 and 16 of Part A, at 12, 18 and 24 weeks during part B and every 6 months on Part C.]

      Overall ORR is the percentage of participants achieving a minimum of partial response (PR) over induction and maintenance treatment based on International Workshop on Chronic Lymphocytic Leukemia (IW-CLL) criteria (Hallek, et al 2008). There are numerous diagnostic tests used for response evaluation including potentially CBC and differential count, marrow aspirate and biopsy, ultrasound of the abdomen, CT scans (chest, pelvis, abdomen) and physical examination. PR is a 50% or greater decrease of measured size of lymphadenopathy, hepatomegaly, splenomegaly as well as blood lymphocytes (over baseline), marrow infiltrate or B-lymphoid nodules and a 50% or greater increase from baseline in platelet count (or level >100,000/micro liter), hemoglobin (or level >11 grams/deciliter), neutrophils (or level >1500/microliter).

    3. Number of Participants With Overall CR [Disease was evaluated after weeks 8 and 16 of Part A, at 12, 18 and 24 weeks during part B and every 6 months on Part C.]

      CR overall (induction and maintenance treatment) was based on International Workshop on Chronic Lymphocytic Leukemia (IW-CLL) criteria (Hallek, et al 2008). There are numerous diagnostic tests used for response evaluation including potentially CBC and differential count, marrow aspirate and biopsy, ultrasound of the abdomen, CT scans (chest, pelvis, abdomen) and physical examination. CR is absence of significant lymphadenopathy (nodes<1.5 centimeters in long axis diameter), hepatomegaly, splenomegaly as well as blood lymphocytes<4000/microliter, normocellular for age marrow with <30% lymphocytes, no B-lymphoid nodules and platelet>100,000/micro liter, hemoglobin>11 grams/deciliter, neutrophils>1500/microliter.

    4. Overall MRD Negative Rate [MRD was assessed after weeks 8 and 16 of Part A, at 12, 18 and 24 weeks during part B and every 6 months on Part C.]

      Overall MRD negative rate is the percentage of participants classified as MRD negative by four color flow cytometry. The assay has a sensitivity of 1 in 10,000 leukocytes.

    5. Transplant Rate [Evaluated up to 36 cycles (approximately 2.75 years) of treatment (Parts A, B and C)]

      Percentage of participants eligible for allogeneic hematopoietic stem cell transplantation (alloHSCT) that are able and willing to proceed to alloHSCT.

    6. Number of Participants With Treatment-Related Grades 1-3 Hyperglycemia During Part A Induction [Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks)]

      Participants ever experiencing a grade 1-3 hyperglycemia event based on CTCAEv4 with treatment attribution of possible, probably or definite as reported on case report forms were counted.

    7. 3-Year Progression-Free Survival (PFS) Probability [Disease was evaluated on treatment after weeks 8 and 16 of Part A, at 12, 18 and 24 weeks during part B and every 6 months on Part C as well as off-treatment every 3 months up to 5 years.]

      3-year PFS is the probability of participants remaining alive and progression-free at 3 years from study entry estimated using Kaplan-Meier methods. Disease progression (PD) per International Workshop on Chronic Lymphocytic Leukemia (IW-CLL) criteria (Hallek, et al 2008) is: the appearance of any new lesion (enlarged lymph node minimum >1.5 centimeters); an increase by 50% in greatest determined diameter of any previous site; an increase in the previously noted enlargement of the liver or spleen by 50% or more or the de novo appearance of hepatomegaly, splenomegaly; a 50% increase of blood lymphocytes (over baseline with level at least 5,000/microliter); occurrence of cytopenia secondary to CLL at least 3 months post treatment including a 50% or greater decrease from baseline in platelet count (or level <100,000/microliter) or a hemoglobin decrease of >2 grams/deciliter (or level <10 grams/deciliter); and transformation to a more aggressive histology.

    8. 3-year Overall Survival (OS) Probability [Median survival follow-up was 45 months (range 31-58 months) in this study cohort.]

      3-year OS is the probability of participants remaining alive at 3 years from study entry estimated using Kaplan-Meier methods.

    9. Number of Participants Completing Part A Treatment [Evaluated up to 4 cycles/16 weeks.]

      Participants counted as completing Part A with either 2 or 4 cycles of treatment per protocol.

    10. Number of Participants Completing Only 2 Cycles of Part A Treatment [Evaluated after 2 cycles/8 weeks of Part A therapy.]

      Participants counted if only completed 2 cycles of Part A treatment per protocol.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Documented CLL/SLL

    • 17p deletion by FISH in 20% or more nuclei on peripheral blood, bone marrow or lymph node

    • Normal organ function

    Exclusion Criteria:
    • Pregnant or breast feeding

    • Current active hepatic or biliary disease

    • Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, tuberculosis and active Hepatitis C

    • History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae

    • Other past or current malignancy. Participants who have been free of malignancy for at least 2 years, or who have a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.

    • Known HIV positive

    • Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months prior to study entry, congestive heart failure, and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities.

    • Significant concurrent uncontrolled medical conditions including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the subject.

    • Positive serology for Hepatitis B or C

    • History of allergic reactions attributed to ofatumumab.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Beth Israel Deaconess Medical CenterBostonMassachusettsUnited States02215
    2Dana-Farber Cancer InstituteBostonMassachusettsUnited States02215

    Sponsors and Collaborators

    • Dana-Farber Cancer Institute
    • National Comprehensive Cancer Network
    • GlaxoSmithKline

    Investigators

    • Principal Investigator: Jennifer R Brown, MD PhD, Dana-Farber Cancer Institute

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Jennifer R. Brown, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute
    ClinicalTrials.gov Identifier:
    NCT01465334
    Other Study ID Numbers:
    • 11-304
    • NCCN Protocol Number: NCCN-001
    • GSK Protocol Number: OFT115580
    First Posted:
    Nov 4, 2011
    Last Update Posted:
    Sep 16, 2019
    Last Verified:
    Sep 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Jennifer R. Brown, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment DetailsParticipants enrolled between December 2011 and November 2014.
    Pre-assignment Detail
    Arm/Group TitleTreatment NaiveRelapsed/Refractory
    Arm/Group DescriptionParticipants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28
    Period Title: Overall Study
    STARTED1515
    Complete Part A Induction1215
    Complete Part B Induction715
    Eligible for Allogeneic Transplant99
    COMPLETED139
    NOT COMPLETED26

    Baseline Characteristics

    Arm/Group TitleTreatment NaiveRelapsed/RefractoryTotal
    Arm/Group DescriptionParticipants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28Total of all reporting groups
    Overall Participants151530
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    64
    65
    65
    Sex: Female, Male (Count of Participants)
    Female
    7
    46.7%
    3
    20%
    10
    33.3%
    Male
    8
    53.3%
    12
    80%
    20
    66.7%
    Region of Enrollment (Count of Participants)
    United States
    15
    100%
    15
    100%
    30
    100%
    Number of Prior Therapies (Count of Participants)
    0
    15
    100%
    0
    0%
    15
    50%
    1
    0
    0%
    6
    40%
    6
    20%
    2
    0
    0%
    4
    26.7%
    4
    13.3%
    3
    0
    0%
    2
    13.3%
    2
    6.7%
    4
    0
    0%
    3
    20%
    3
    10%
    Time from Diagnosis to First Therapy (months) [Mean (Full Range) ]
    Mean (Full Range) [months]
    6.9
    23
    12.4
    Time from Diagnosis to Start on Trial (months) [Mean (Full Range) ]
    Mean (Full Range) [months]
    6.8
    59.4
    27.6
    Whole Exome Sequencing-Mutations (mutations) [Median (Full Range) ]
    Median (Full Range) [mutations]
    22
    20
    21
    Whole Exome Sequencing-Copy Number Alterations (Events) [Median (Full Range) ]
    Median (Full Range) [Events]
    12.5
    14
    14

    Outcome Measures

    1. Primary Outcome
    TitleInduction Overall Response Rate (ORR)
    DescriptionInduction ORR is the percentage of participants achieving a minimum of partial response (PR) over induction treatment based on International Workshop on Chronic Lymphocytic Leukemia (IW-CLL) criteria (Hallek, et al 2008). There are numerous diagnostic tests used for response evaluation including potentially CBC and differential count, marrow aspirate and biopsy, ultrasound of the abdomen, CT scans (chest, pelvis, abdomen) and physical examination. PR is a 50% or greater decrease of measured size of lymphadenopathy, hepatomegaly, splenomegaly as well as blood lymphocytes (over baseline), marrow infiltrate or B-lymphoid nodules and a 50% or greater increase from baseline in platelet count (or level >100,000/micro liter), hemoglobin (or level >11 grams/deciliter), neutrophils (or level >1500/microliter).
    Time FrameDisease was evaluated after weeks 8 and 16 of Part A and at 12, 18 and 24 weeks during part B.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTreatment NaiveRelapsed/Refractory
    Arm/Group DescriptionParticipants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28
    Measure Participants1515
    Number (90% Confidence Interval) [percentage of participants]
    73
    486.7%
    60
    400%
    2. Secondary Outcome
    TitleNumber of Participants Achieving Induction Complete Response (CR)
    DescriptionCR over induction treatment was based on International Workshop on Chronic Lymphocytic Leukemia (IW-CLL) criteria (Hallek, et al 2008). There are numerous diagnostic tests used for response evaluation including potentially CBC and differential count, marrow aspirate and biopsy, ultrasound of the abdomen, CT scans (chest, pelvis, abdomen) and physical examination. CR is absence of significant lymphadenopathy (nodes<1.5 centimeters in long axis diameter), hepatomegaly, splenomegaly as well as blood lymphocytes<4000/microliter, normocellular for age marrow with <30% lymphocytes, no B-lymphoid nodules and platelet>100,000/micro liter, hemoglobin>11 grams/deciliter, neutrophils>1500/microliter.
    Time FrameDisease was evaluated after weeks 8 and 16 of Part A and at 12, 18 and 24 weeks during part B.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTreatment NaiveRelapsed/Refractory
    Arm/Group DescriptionParticipants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28
    Measure Participants1515
    Number [participants]
    0
    0%
    0
    0%
    3. Secondary Outcome
    TitleOverall Objective Response Rate (ORR)
    DescriptionOverall ORR is the percentage of participants achieving a minimum of partial response (PR) over induction and maintenance treatment based on International Workshop on Chronic Lymphocytic Leukemia (IW-CLL) criteria (Hallek, et al 2008). There are numerous diagnostic tests used for response evaluation including potentially CBC and differential count, marrow aspirate and biopsy, ultrasound of the abdomen, CT scans (chest, pelvis, abdomen) and physical examination. PR is a 50% or greater decrease of measured size of lymphadenopathy, hepatomegaly, splenomegaly as well as blood lymphocytes (over baseline), marrow infiltrate or B-lymphoid nodules and a 50% or greater increase from baseline in platelet count (or level >100,000/micro liter), hemoglobin (or level >11 grams/deciliter), neutrophils (or level >1500/microliter).
    Time FrameDisease was evaluated after weeks 8 and 16 of Part A, at 12, 18 and 24 weeks during part B and every 6 months on Part C.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTreatment NaiveRelapsed/Refractory
    Arm/Group DescriptionParticipants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28
    Measure Participants1515
    Number (90% Confidence Interval) [percentage of participants]
    80
    533.3%
    67
    446.7%
    4. Secondary Outcome
    TitleNumber of Participants With Overall CR
    DescriptionCR overall (induction and maintenance treatment) was based on International Workshop on Chronic Lymphocytic Leukemia (IW-CLL) criteria (Hallek, et al 2008). There are numerous diagnostic tests used for response evaluation including potentially CBC and differential count, marrow aspirate and biopsy, ultrasound of the abdomen, CT scans (chest, pelvis, abdomen) and physical examination. CR is absence of significant lymphadenopathy (nodes<1.5 centimeters in long axis diameter), hepatomegaly, splenomegaly as well as blood lymphocytes<4000/microliter, normocellular for age marrow with <30% lymphocytes, no B-lymphoid nodules and platelet>100,000/micro liter, hemoglobin>11 grams/deciliter, neutrophils>1500/microliter.
    Time FrameDisease was evaluated after weeks 8 and 16 of Part A, at 12, 18 and 24 weeks during part B and every 6 months on Part C.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTreatment NaiveRelapsed/Refractory
    Arm/Group DescriptionParticipants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28
    Measure Participants1515
    Number [participants]
    2
    13.3%
    0
    0%
    5. Secondary Outcome
    TitleOverall MRD Negative Rate
    DescriptionOverall MRD negative rate is the percentage of participants classified as MRD negative by four color flow cytometry. The assay has a sensitivity of 1 in 10,000 leukocytes.
    Time FrameMRD was assessed after weeks 8 and 16 of Part A, at 12, 18 and 24 weeks during part B and every 6 months on Part C.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTreatment NaiveRelapsed/Refractory
    Arm/Group DescriptionParticipants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28
    Measure Participants1515
    Number (90% Confidence Interval) [percentage of participants]
    80
    533.3%
    53
    353.3%
    6. Secondary Outcome
    TitleTransplant Rate
    DescriptionPercentage of participants eligible for allogeneic hematopoietic stem cell transplantation (alloHSCT) that are able and willing to proceed to alloHSCT.
    Time FrameEvaluated up to 36 cycles (approximately 2.75 years) of treatment (Parts A, B and C)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTreatment NaiveRelapsed/Refractory
    Arm/Group DescriptionParticipants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28
    Measure Participants1515
    Number (90% Confidence Interval) [percentage of participants]
    43
    286.7%
    43
    286.7%
    7. Secondary Outcome
    TitleNumber of Participants With Treatment-Related Grades 1-3 Hyperglycemia During Part A Induction
    DescriptionParticipants ever experiencing a grade 1-3 hyperglycemia event based on CTCAEv4 with treatment attribution of possible, probably or definite as reported on case report forms were counted.
    Time FrameAdverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTreatment NaiveRelapsed/Refractory
    Arm/Group DescriptionParticipants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28
    Measure Participants1515
    Number [participants]
    5
    33.3%
    6
    40%
    8. Secondary Outcome
    Title3-Year Progression-Free Survival (PFS) Probability
    Description3-year PFS is the probability of participants remaining alive and progression-free at 3 years from study entry estimated using Kaplan-Meier methods. Disease progression (PD) per International Workshop on Chronic Lymphocytic Leukemia (IW-CLL) criteria (Hallek, et al 2008) is: the appearance of any new lesion (enlarged lymph node minimum >1.5 centimeters); an increase by 50% in greatest determined diameter of any previous site; an increase in the previously noted enlargement of the liver or spleen by 50% or more or the de novo appearance of hepatomegaly, splenomegaly; a 50% increase of blood lymphocytes (over baseline with level at least 5,000/microliter); occurrence of cytopenia secondary to CLL at least 3 months post treatment including a 50% or greater decrease from baseline in platelet count (or level <100,000/microliter) or a hemoglobin decrease of >2 grams/deciliter (or level <10 grams/deciliter); and transformation to a more aggressive histology.
    Time FrameDisease was evaluated on treatment after weeks 8 and 16 of Part A, at 12, 18 and 24 weeks during part B and every 6 months on Part C as well as off-treatment every 3 months up to 5 years.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTreatment NaiveRelapsed/Refractory
    Arm/Group DescriptionParticipants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28
    Measure Participants1515
    Number (95% Confidence Interval) [percentage probability]
    53
    25
    9. Secondary Outcome
    Title3-year Overall Survival (OS) Probability
    Description3-year OS is the probability of participants remaining alive at 3 years from study entry estimated using Kaplan-Meier methods.
    Time FrameMedian survival follow-up was 45 months (range 31-58 months) in this study cohort.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTreatment NaiveRelapsed/Refractory
    Arm/Group DescriptionParticipants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28
    Measure Participants1515
    Number (95% Confidence Interval) [percentage probability]
    66
    53
    10. Secondary Outcome
    TitleNumber of Participants Completing Part A Treatment
    DescriptionParticipants counted as completing Part A with either 2 or 4 cycles of treatment per protocol.
    Time FrameEvaluated up to 4 cycles/16 weeks.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTreatment NaiveRelapsed/Refractory
    Arm/Group DescriptionParticipants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28
    Measure Participants1515
    Number [participants]
    12
    80%
    15
    100%
    11. Secondary Outcome
    TitleNumber of Participants Completing Only 2 Cycles of Part A Treatment
    DescriptionParticipants counted if only completed 2 cycles of Part A treatment per protocol.
    Time FrameEvaluated after 2 cycles/8 weeks of Part A therapy.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleTreatment NaiveRelapsed/Refractory
    Arm/Group DescriptionParticipants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28
    Measure Participants1515
    Number [participants]
    0
    0%
    0
    0%

    Adverse Events

    Time FrameAdverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days.
    Adverse Event Reporting Description Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.
    Arm/Group TitleTreatment NaiveRelapsed/Refractory
    Arm/Group DescriptionParticipants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy. (cycle duration=28 days) Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants who have not experienced a clinical complete response with no residual detectable disease after Part A will continue on to Part B. Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants who have experienced at least stable disease in Parts A and B can continue on to Part C. Participants who are eligible may instead proceed to stem cell transplantation after Parts A and B. Part C: Maintenance with Ofatumumab + Alemtuzumab up to 2 years Ofatumumab: 1000 mg IV every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy. (cycle duration=28 days) Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants who have not experienced a clinical complete response with no residual detectable disease after Part A will continue on to Part B. Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants who have experienced at least stable disease in Parts A and B can continue on to Part C. Participants who are eligible may instead proceed to stem cell transplantation after Parts A and B. Part C: Maintenance with Ofatumumab + Alemtuzumab up to 2 years Ofatumumab: 1000 mg IV every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28
    All Cause Mortality
    Treatment NaiveRelapsed/Refractory
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total7/15 (46.7%) 6/15 (40%)
    Serious Adverse Events
    Treatment NaiveRelapsed/Refractory
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total11/15 (73.3%) 9/15 (60%)
    Blood and lymphatic system disorders
    Anemia1/15 (6.7%) 1/15 (6.7%)
    Febrile neutropenia3/15 (20%) 1/15 (6.7%)
    General disorders
    Infusion related reaction2/15 (13.3%) 0/15 (0%)
    Investigations
    Growth hormone abnormal1/15 (6.7%) 0/15 (0%)
    Lymphocyte count decreased1/15 (6.7%) 2/15 (13.3%)
    Lymphocyte count increased0/15 (0%) 1/15 (6.7%)
    Neutrophil count decreased6/15 (40%) 7/15 (46.7%)
    Platelet count decreased2/15 (13.3%) 1/15 (6.7%)
    White blood cell decreased4/15 (26.7%) 5/15 (33.3%)
    Metabolism and nutrition disorders
    Hyperglycemia3/15 (20%) 3/15 (20%)
    Musculoskeletal and connective tissue disorders
    Myalgia1/15 (6.7%) 0/15 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Treatment related secondary malignancy1/15 (6.7%) 0/15 (0%)
    Respiratory, thoracic and mediastinal disorders
    Pneumonitis0/15 (0%) 1/15 (6.7%)
    Skin and subcutaneous tissue disorders
    Urticaria1/15 (6.7%) 0/15 (0%)
    Other (Not Including Serious) Adverse Events
    Treatment NaiveRelapsed/Refractory
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total15/15 (100%) 14/15 (93.3%)
    Blood and lymphatic system disorders
    Anemia9/15 (60%) 9/15 (60%)
    Blood and lymphatic system disorders - Other0/15 (0%) 2/15 (13.3%)
    Febrile neutropenia0/15 (0%) 1/15 (6.7%)
    Cardiac disorders
    Acute coronary syndrome0/15 (0%) 1/15 (6.7%)
    Cardiac disorders - Other1/15 (6.7%) 1/15 (6.7%)
    Chest pain - cardiac0/15 (0%) 2/15 (13.3%)
    Palpitations2/15 (13.3%) 0/15 (0%)
    Ear and labyrinth disorders
    Ear and labyrinth disorders - Other1/15 (6.7%) 1/15 (6.7%)
    Ear and labyrinth disorders - Other, specify0/15 (0%) 0/15 (0%)
    Vertigo1/15 (6.7%) 0/15 (0%)
    Eye disorders
    Blurred vision2/15 (13.3%) 0/15 (0%)
    Dry eye1/15 (6.7%) 0/15 (0%)
    Eye disorders - Other2/15 (13.3%) 0/15 (0%)
    Flashing lights0/15 (0%) 1/15 (6.7%)
    Gastrointestinal disorders
    Abdominal pain2/15 (13.3%) 1/15 (6.7%)
    Colonic ulcer1/15 (6.7%) 1/15 (6.7%)
    Constipation3/15 (20%) 3/15 (20%)
    Diarrhea4/15 (26.7%) 2/15 (13.3%)
    Dry mouth1/15 (6.7%) 0/15 (0%)
    Duodenal hemorrhage0/15 (0%) 2/15 (13.3%)
    Flatulence0/15 (0%) 1/15 (6.7%)
    Gastritis0/15 (0%) 1/15 (6.7%)
    Gastroesophageal reflux disease2/15 (13.3%) 0/15 (0%)
    Gastrointestinal disorders - Other2/15 (13.3%) 2/15 (13.3%)
    Nausea5/15 (33.3%) 0/15 (0%)
    Nausea0/15 (0%) 6/15 (40%)
    Oral pain0/15 (0%) 1/15 (6.7%)
    Vomiting2/15 (13.3%) 3/15 (20%)
    General disorders
    Chills4/15 (26.7%) 1/15 (6.7%)
    Edema face2/15 (13.3%) 0/15 (0%)
    Edema limbs4/15 (26.7%) 3/15 (20%)
    Edema trunk1/15 (6.7%) 0/15 (0%)
    Fatigue10/15 (66.7%) 9/15 (60%)
    Fever10/15 (66.7%) 7/15 (46.7%)
    General disorders and administration site conditions - Other1/15 (6.7%) 3/15 (20%)
    Infusion related reaction3/15 (20%) 1/15 (6.7%)
    Injection site reaction1/15 (6.7%) 0/15 (0%)
    Irritability1/15 (6.7%) 0/15 (0%)
    Localized edema1/15 (6.7%) 1/15 (6.7%)
    Malaise1/15 (6.7%) 1/15 (6.7%)
    Pain4/15 (26.7%) 1/15 (6.7%)
    Immune system disorders
    Allergic reaction2/15 (13.3%) 0/15 (0%)
    Infections and infestations
    Infections and infestations - Other2/15 (13.3%) 0/15 (0%)
    Laryngitis0/15 (0%) 1/15 (6.7%)
    Papulopustular rash1/15 (6.7%) 0/15 (0%)
    Sinusitis1/15 (6.7%) 0/15 (0%)
    Skin infection0/15 (0%) 2/15 (13.3%)
    Upper respiratory infection1/15 (6.7%) 2/15 (13.3%)
    Injury, poisoning and procedural complications
    Bruising1/15 (6.7%) 0/15 (0%)
    Fracture1/15 (6.7%) 0/15 (0%)
    Investigations
    Alanine aminotransferase increased6/15 (40%) 3/15 (20%)
    Alkaline phosphatase increased4/15 (26.7%) 2/15 (13.3%)
    Aspartate aminotransferase increased9/15 (60%) 4/15 (26.7%)
    Blood bilirubin increased2/15 (13.3%) 2/15 (13.3%)
    Creatinine increased2/15 (13.3%) 3/15 (20%)
    Investigations - Other1/15 (6.7%) 0/15 (0%)
    Neutrophil count decreased7/15 (46.7%) 8/15 (53.3%)
    Platelet count decreased4/15 (26.7%) 8/15 (53.3%)
    Weight gain1/15 (6.7%) 0/15 (0%)
    White blood cell decreased5/15 (33.3%) 8/15 (53.3%)
    Metabolism and nutrition disorders
    Anorexia2/15 (13.3%) 1/15 (6.7%)
    Dehydration0/15 (0%) 2/15 (13.3%)
    Hyperglycemia6/15 (40%) 6/15 (40%)
    Hyperkalemia1/15 (6.7%) 1/15 (6.7%)
    Hypermagnesemia1/15 (6.7%) 0/15 (0%)
    Hypernatremia1/15 (6.7%) 0/15 (0%)
    Hyperuricemia1/15 (6.7%) 2/15 (13.3%)
    Hypoalbuminemia0/15 (0%) 1/15 (6.7%)
    Hypocalcemia7/15 (46.7%) 4/15 (26.7%)
    Hypoglycemia1/15 (6.7%) 1/15 (6.7%)
    Hypokalemia1/15 (6.7%) 0/15 (0%)
    Hypokalemia0/15 (0%) 2/15 (13.3%)
    Hypomagnesemia0/15 (0%) 2/15 (13.3%)
    Hyponatremia2/15 (13.3%) 4/15 (26.7%)
    Hypophosphatemia3/15 (20%) 2/15 (13.3%)
    Metabolism and nutrition disorders - Other2/15 (13.3%) 0/15 (0%)
    Musculoskeletal and connective tissue disorders
    Arthritis1/15 (6.7%) 0/15 (0%)
    Back pain1/15 (6.7%) 2/15 (13.3%)
    Bone pain2/15 (13.3%) 1/15 (6.7%)
    Chest wall pain0/15 (0%) 1/15 (6.7%)
    Generalized muscle weakness0/15 (0%) 1/15 (6.7%)
    Muscle weakness lower limb0/15 (0%) 2/15 (13.3%)
    Musculoskeletal and connective tissue disorder - Other2/15 (13.3%) 3/15 (20%)
    Myalgia2/15 (13.3%) 0/15 (0%)
    Neck pain1/15 (6.7%) 0/15 (0%)
    Pain in extremity1/15 (6.7%) 0/15 (0%)
    Nervous system disorders
    Dizziness1/15 (6.7%) 0/15 (0%)
    Headache4/15 (26.7%) 3/15 (20%)
    Myelitis0/15 (0%) 1/15 (6.7%)
    Nervous system disorders - Other3/15 (20%) 3/15 (20%)
    Paresthesia1/15 (6.7%) 0/15 (0%)
    Peripheral motor neuropathy1/15 (6.7%) 2/15 (13.3%)
    Peripheral sensory neuropathy1/15 (6.7%) 1/15 (6.7%)
    Somnolence1/15 (6.7%) 0/15 (0%)
    Syncope0/15 (0%) 1/15 (6.7%)
    Tremor0/15 (0%) 1/15 (6.7%)
    Psychiatric disorders
    Anxiety4/15 (26.7%) 3/15 (20%)
    Confusion1/15 (6.7%) 1/15 (6.7%)
    Depression1/15 (6.7%) 0/15 (0%)
    Insomnia3/15 (20%) 4/15 (26.7%)
    Restlessness1/15 (6.7%) 0/15 (0%)
    Renal and urinary disorders
    Renal and urinary disorders - Other1/15 (6.7%) 0/15 (0%)
    Urinary frequency4/15 (26.7%) 2/15 (13.3%)
    Urinary retention1/15 (6.7%) 0/15 (0%)
    Reproductive system and breast disorders
    Pelvic pain2/15 (13.3%) 1/15 (6.7%)
    Respiratory, thoracic and mediastinal disorders
    Cough6/15 (40%) 7/15 (46.7%)
    Dyspnea5/15 (33.3%) 6/15 (40%)
    Epistaxis0/15 (0%) 1/15 (6.7%)
    Laryngeal inflammation1/15 (6.7%) 0/15 (0%)
    Nasal congestion3/15 (20%) 2/15 (13.3%)
    Pleural effusion1/15 (6.7%) 0/15 (0%)
    Pneumonitis2/15 (13.3%) 1/15 (6.7%)
    Postnasal drip1/15 (6.7%) 1/15 (6.7%)
    Respiratory failure0/15 (0%) 1/15 (6.7%)
    Respiratory, thoracic and mediastinal disorders - Other3/15 (20%) 2/15 (13.3%)
    Sore throat1/15 (6.7%) 0/15 (0%)
    Wheezing1/15 (6.7%) 1/15 (6.7%)
    Skin and subcutaneous tissue disorders
    Alopecia1/15 (6.7%) 1/15 (6.7%)
    Bullous dermatitis2/15 (13.3%) 0/15 (0%)
    Dry skin1/15 (6.7%) 0/15 (0%)
    Erythema multiforme2/15 (13.3%) 0/15 (0%)
    Hyperhidrosis4/15 (26.7%) 2/15 (13.3%)
    Lipohypertrophy1/15 (6.7%) 0/15 (0%)
    Photosensitivity1/15 (6.7%) 0/15 (0%)
    Pruritus3/15 (20%) 0/15 (0%)
    Rash acneiform1/15 (6.7%) 0/15 (0%)
    Rash maculo-papular3/15 (20%) 0/15 (0%)
    Skin and subcutaneous tissue disorders - Other5/15 (33.3%) 3/15 (20%)
    Urticaria2/15 (13.3%) 0/15 (0%)
    Vascular disorders
    Flushing0/15 (0%) 1/15 (6.7%)
    Hematoma0/15 (0%) 1/15 (6.7%)
    Hypertension1/15 (6.7%) 0/15 (0%)
    Superficial thrombophlebitis1/15 (6.7%) 0/15 (0%)
    Thromboembolic event1/15 (6.7%) 0/15 (0%)
    Vascular disorders - Other0/15 (0%) 1/15 (6.7%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleJennifer R. Brown, MD, PhD
    OrganizationDana-Farber Cancer Institute
    Phone(617) 632-3316
    EmailJennifer_Brown@dfci.harvard.edu
    Responsible Party:
    Jennifer R. Brown, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute
    ClinicalTrials.gov Identifier:
    NCT01465334
    Other Study ID Numbers:
    • 11-304
    • NCCN Protocol Number: NCCN-001
    • GSK Protocol Number: OFT115580
    First Posted:
    Nov 4, 2011
    Last Update Posted:
    Sep 16, 2019
    Last Verified:
    Sep 1, 2019