Clinical trial NCT01191190: Ofatumumab and High-dose Methylprednisolone in Patients With Chronic Lymphocytic Leukemia (CLL)
Official title: A Phase II Study of Ofatumumab in Combination With High-dose Methylprednisolone in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: CLL
Keywords: Leukemia
Chronic leukemia
Chronic Lymphocytic Leukemia
Relapsed
Refractory
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2010-08-30
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Patients who have relapsed/refractory CLL and require therapy as per iwCLL guidelines will be eligible. Subjects will receive a treatment with ofatumumab and HDMP for three consecutive 4 week cycles. The primary endpoint is to determine the complete response (CR) to therapy and the secondary endpoints will assess the safety and tolerability of the regimen, the impact of the treatment on progression free, treatment free, overall survival, and pharmacokinetics of ofatumumab. Patients will receive allopurinol for tumor-lysis prophylaxis and antimicrobial prophylaxis.

Detailed description: Patients who have relapsed/refractory CLL and require therapy as per iwCLL guidelines will be eligible. Subjects will receive a treatment with ofatumumab and HDMP for three consecutive 4 week cycles. The primary endpoint is to determine the complete response (CR) to therapy and the secondary endpoints will assess the safety and tolerability of the regimen, the impact of the treatment on progression free, treatment free, overall survival, and pharmacokinetics of ofatumumab. Cycles 1-3 will be administered without scheduled interruption every 28 days for a total of 12 weeks of therapy. Patients will receive allopurinol for tumor-lysis prophylaxis and antimicrobial prophylaxis. Blood glucose levels will be monitored immediately after HDMP infusion by finger stick glucometry. Two months following completion of treatment a response assessment will occur per iwCLL guidelines. The treatment will be administered as outpatient, and each cycle will be four weeks in duration.

Eligibility criteria: Inclusion Criteria:

1. Previously treated patients with a diagnosis of CLL
2. Previous treatment with any monoclonal antibody or chemotherapy regardless of response as defined by the iwCLL Working Group Guidelines as evidenced by:

   * progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia
   * massive (i.e. at least 6cm below the left costal margin) or progressive or symptomatic splenomegaly
   * massive nodes (i.e. at least 10cm in longest diameter) or progressive or symptomatic lymphadenopathy.
   * progressive lymphocytosis with an increase of more than 50% over a 2-month period or lymphocyte doubling time (LDT) of less than 6 months.
   * autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy (See Section 10.2)
3. Constitutional symptoms, defined as any one or more of the following disease-related symptoms or signs: unintentional weight loss of 10% or more within the previous 6 months significant fatigue (i.e. ECOG PS 2 or worse, inability to work or perform usual activities), fevers higher than 100.5ºF or 38.0ºC for 2 or more weeks without other evidence of infection, night sweats for more than 1 month without evidence of infection
4. Subjects must be 18 years of age or older, male or female.
5. ECOG performance status of 0-2.
6. Subjects must be able to give informed consent.
7. Females of child bearing potential(FCBP)† must have a negative serum or urine pregnancy test within 10 - 14 days prior to and again within 24 hours of starting treatment and agree to use a medically accepted contraceptive method for the duration of this study.

Exclusion Criteria:

1. Hepatitis BsAg positive, Hepatitis BcAb positive, and Hepatitis C positive patients.
2. Known HIV positive patients.
3. Diabetics.
4. Patients with uncontrolled Autoimmune Hemolytic Anemia (AIHA) or autoimmune thrombocytopenia (ITP).
5. Screening laboratory values within these ranges: platelets \<50 x 109/L, neutrophils \<1.0 x 109/L, creatinine \>2.0 times upper normal limit,total bilirubin \>1.5 times upper normal limit (unless a known history of Gilbert's disease), ALT \>2.5 times upper normal limit (unless due to disease involvement of liver), alkaline phosphatase \>2.5 times upper normal limit (unless due to disease involvement of the liver or bone marrow)
6. Inability to provide informed consent.
7. Concurrent malignancy (excluding basal and squamous cell skin cancers).
8. Active fungal, bacterial, and/or viral infection.
9. History of peptic ulcer disease resulting in GI bleeding within the last 6 months.
10. Untreated metabolic disorders such as hypothyroidism and Cushing's disease.
11. History of steroid-induced psychosis.
12. Estimated life expectancy of less than 3 months by the investigator's best clinical judgment.
13. Serious medical condition that would render the subject medically unstable.
14. Women who are pregnant or breast-feeding.
15. History of Pancreatitis.
16. History of Diverticulitis.
17. Patients with known hypersensitivity to ofatumumab or known history of anaphylaxis to Rituximab or alemtuzumab.
18. Concurrent use of other anti-cancer agents or treatments.
19. Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).

Primary outcomes:
measure: IwCLL-WG Defined Complete Response (CR)
timeFrame: 2 months
Secondary outcomes:
measure: IwCLL-WG Defined Overall Response Rate (ORR)
timeFrame: 2 months
measure: IwCLL-WG Defined Nodular Partial Response (PR)
timeFrame: 2 months
measure: IwCLL-WG Defined Partial Response (PR)
timeFrame: 2 months
measure: IwCLL-WG Defined Stable Disease (SD)
timeFrame: 2 months
measure: IwCLL-WG Defined Progressive Disease (PD)
timeFrame: 2 months
measure: Progression-free Survival (PFS)
timeFrame: 2 years
measure: Treatment-Free Survival
timeFrame: 2 years
measure: Safety and Tolerability Measured Via Adverse Events
timeFrame: 2 years
measure: Detectable Minimal Residual Disease (MRD)
timeFrame: 2 years
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: La Jolla
country: United States
facility: University of California San Diego, Moores Cancer Center
state: California
Study officials:
affiliation: University of California, San Diego
name: Januario Castro, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Director of the CLL Research Consortium and University of California San Diego
name: Thomas J Kipps, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Castro JE, James DF, Sandoval-Sus JD, Jain S, Bole J, Rassenti L, Kipps TJ. Rituximab in combination with high-dose methylprednisolone for the treatment of chronic lymphocytic leukemia. Leukemia. 2009 Oct;23(10):1779-89. doi: 10.1038/leu.2009.133. Epub 2009 Aug 20.
citation: Castro JE, Sandoval-Sus JD, Bole J, Rassenti L, Kipps TJ. Rituximab in combination with high-dose methylprednisolone for the treatment of fludarabine refractory high-risk chronic lymphocytic leukemia. Leukemia. 2008 Nov;22(11):2048-53. doi: 10.1038/leu.2008.214. Epub 2008 Aug 28.