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

NCT ID: NCT01465334

Last Updated: 2023-08-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-31
• Study Completion Date: 2017-01-31

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.

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.

Conditions

CLL; SLL

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Ofatumumab

Intervention Type: DRUG

High-Dose Methylprednisolone

Intervention Type: DRUG

Alemtuzumab

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

Ofatumumab

Intervention Type: DRUG

High-Dose Methylprednisolone

Intervention Type: DRUG

Alemtuzumab

Intervention Type: DRUG

Interventions

Ofatumumab

Intervention Type: DRUG

High-Dose Methylprednisolone

Intervention Type: DRUG

Alemtuzumab

Intervention Type: DRUG

Other Intervention Names

GSK 1841157; HDMP; Campath-1H

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Comprehensive Cancer Network

NETWORK

Sponsor Role: collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Jennifer R. Brown, MD, PhD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jennifer R Brown, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Countries

United States

References

Davids MS, Kim HT, Yu L, De Maeyer G, McDonough M, Vartanov AR, Langey R, Fernandes SM, Hellman JM, Francoeur K, Arnason J, Jacobsen ED, LaCasce AS, Fisher DC, Brown JR. Ofatumumab plus high dose methylprednisolone followed by ofatumumab plus alemtuzumab to achieve maximal cytoreduction prior to allogeneic transplantation for 17p deleted or TP53 mutated chronic lymphocytic leukemia. Leuk Lymphoma. 2019 May;60(5):1312-1315. doi: 10.1080/10428194.2018.1519814. Epub 2018 Oct 15.

Reference Type: RESULT

PMID: 30322319 (View on PubMed)

Other Identifiers

NCCN Protocol Number: NCCN-001

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

GSK Protocol Number: OFT115580

Identifier Type: OTHER

Identifier Source: secondary_id

11-304

Identifier Type: -

Identifier Source: org_study_id