Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01465334
Recruitment Status : Terminated (Terminated early due to change in practice.)
First Posted : November 4, 2011
Results First Posted : June 26, 2019
Last Update Posted : June 26, 2019
Sponsor:
Collaborators:
National Comprehensive Cancer Network
GlaxoSmithKline
Information provided by (Responsible Party):
Jennifer R. Brown, MD, PhD, Dana-Farber Cancer Institute

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 disease Intervention/treatment Phase
CLL SLL Drug: Ofatumumab Drug: High-Dose Methylprednisolone Drug: Alemtuzumab 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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
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 : December 2011
Actual Primary Completion Date : November 2014
Actual Study Completion Date : January 2017


Arm Intervention/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 Name: GSK 1841157

Drug: High-Dose Methylprednisolone
Other Name: HDMP

Drug: Alemtuzumab
Other Name: 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 Name: GSK 1841157

Drug: High-Dose Methylprednisolone
Other Name: HDMP

Drug: Alemtuzumab
Other Name: Campath-1H




Primary Outcome Measures :
  1. Induction Overall Response Rate (ORR) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Evaluated after 2 cycles/8 weeks of Part A therapy. ]
    Participants counted if only completed 2 cycles of Part A treatment per protocol.



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.


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

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.

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): NCT01465334


Locations
Layout table for location information
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Dana-Farber Cancer Institute
National Comprehensive Cancer Network
GlaxoSmithKline
Investigators
Layout table for investigator information
Principal Investigator: Jennifer R Brown, MD PhD Dana-Farber Cancer Institute

Publications of Results:
Layout table for additonal information
Responsible Party: Jennifer R. Brown, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01465334     History of Changes
Other Study ID Numbers: 11-304
NCCN Protocol Number: NCCN-001 ( Other Grant/Funding Number: NCCN )
GSK Protocol Number: OFT115580 ( Other Identifier: GSK )
First Posted: November 4, 2011    Key Record Dates
Results First Posted: June 26, 2019
Last Update Posted: June 26, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Jennifer R. Brown, MD, PhD, Dana-Farber Cancer Institute:
17p Deletion CLL

Additional relevant MeSH terms:
Layout table for MeSH terms
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Alemtuzumab
Ofatumumab
Antibodies, Monoclonal
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Protective Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antineoplastic Agents, Immunological
Immunologic Factors