Clinical trial NCT01465334: Ofatumumab With High Dose Methylprednisone Followed by Ofatumumab and Alemtuzumab in 17p CLL
Official title: A Phase II Study of Ofatumumab-High Dose Methylprednisolone Followed by Ofatumumab-Alemtuzumab in 17p Deletion CLL
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: CLL
SLL
Keywords: 17p Deletion CLL
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Comprehensive Cancer Network
name: GlaxoSmithKline
First posted: 2011-11-04
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Induction Overall Response Rate (ORR)
timeFrame: Disease was evaluated after weeks 8 and 16 of Part A and at 12, 18 and 24 weeks during part B.
Secondary outcomes:
measure: Number of Participants Achieving Induction Complete Response (CR)
timeFrame: Disease was evaluated after weeks 8 and 16 of Part A and at 12, 18 and 24 weeks during part B.
measure: Overall Objective Response Rate (ORR)
timeFrame: 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.
measure: Number of Participants With Overall CR
timeFrame: 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.
measure: Overall MRD Negative Rate
timeFrame: 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.
measure: Transplant Rate
timeFrame: Evaluated up to 36 cycles (approximately 2.75 years) of treatment (Parts A, B and C)
measure: Number of Participants With Treatment-Related Grades 1-3 Hyperglycemia During Part A Induction
timeFrame: 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)
measure: 3-Year Progression-Free Survival (PFS) Probability
timeFrame: 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.
measure: 3-year Overall Survival (OS) Probability
timeFrame: Median survival follow-up was 45 months (range 31-58 months) in this study cohort.
measure: Number of Participants Completing Part A Treatment
timeFrame: Evaluated up to 4 cycles/16 weeks.
measure: Number of Participants Completing Only 2 Cycles of Part A Treatment
timeFrame: Evaluated after 2 cycles/8 weeks of Part A therapy.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Jennifer R Brown, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.