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Phase II Study of Ofatumumab in Combination With High Dose Methylprednisolone Followed by Ofatumumab and Lenalidomide Consolidative Therapy for the Treatment of Untreated CLL/SLL The HiLOG Trial

Phase 2
18 Years
Open (Enrolling)
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

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Trial Information

Phase II Study of Ofatumumab in Combination With High Dose Methylprednisolone Followed by Ofatumumab and Lenalidomide Consolidative Therapy for the Treatment of Untreated CLL/SLL The HiLOG Trial

This is a phase II, single institution, and non-randomized study of patients with untreated
CLL/SLL, utilizing a two-stage trial design. The primary endpoint for this trial is the
combined complete and partial response rate (at 3 months-the end of cycle 3) to the protocol
therapy. We anticipate this trial will have a complete response (CR) and partial response
(PR) rate of at least 80%.

A two-stage design is employed for this trial. The null/unacceptable CR+PR response rate is
≤ 60% while the anticipated true response rate to the protocol treatment is at least 80% for
each disease cohort. At the first stage, 26 patients will be accrued to the trial. If 15 or
fewer of these patients respond, then the trial will be terminated early and the response
rate to the protocol treatment will be deemed unacceptable (≤ 60%). Otherwise, if more than
15 patients respond during the first stage, an additional 19 patients will be enrolled to
this trial during stage 2 for a total of 45 patients. If 32 or fewer of these 45 patients
respond to the protocol treatment at the end of stage 2, no further investigation of the
protocol treatment is considered warranted. On the other hand, if more than 32 patients out
of the 45 enrolled patients respond, the protocol treatment will be considered promising. If
the true response rate is ≤ 60%, the probability of ending the trial at stage 1 is 0.48. If,
however, the true response rate is at least 80%, then the probability of ending the trial at
stage 1 is only 0.01. This two-stage design has an overall alpha level of 0.045 and a power
of 0.90.

Inclusion Criteria:

- Understand and voluntarily sign an informed consent form

- Able to adhere to the study visit schedule and other protocol requirements

- Patients must have histologically or cytologically confirmed CD5+/CD20+ B-Cell
chronic lymphocytic leukemia or small lymphocytic lymphoma. The diagnosis of CLL is
based upon the National Comprehensive Cancer Network (NCCN) guidelines. Any outside
pathology slides used as inclusion criteria for the patient will be reviewed at this
institution to confirm the diagnosis. The patient must meet all of the following CLL
criteria to participate in this study: absolute lymphocyte count > 5000/μL; CD20+ and
CD5+; Bone marrow lymphocytes ≥ 30%; Or previous confirmed diagnosis of CLL/SLL with
less than 5000/μl or less than 30% lymphocytes in bone marrow.

- Patients are eligible if they have stage III or IV disease. Patients with stage 0, I
or II disease will be eligible if they have evidence of active disease defined as one
or more of the following signs/symptoms: Documented weight loss of ≥ 10% over a 6
month period; Febrile episodes of 38 degrees Celsius (100.5 degrees F) or greater for
greater than 2 weeks without evidence of infection; Massive or progressive
splenomegaly defined as > 6 cm below the left costal margin; Massive (> 10 cm in
longest diameter) or progressive lymphadenopathy.

- Patient has not received any prior treatment for CLL in the past.

- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 at study entry

- Laboratory test results within these ranges: Absolute neutrophil count ≥ 1000/mm³;
Platelet count ≥ 50,000 /mm³; Renal function assessed by calculated creatinine
clearance ≥ 30ml/min by Cockcroft-Gault formula; Total bilirubin ≤ 1.5 x upper limit
of normal (ULN); aspartic transaminase (AST/SGOT) and alanine transaminase (ALT/SGPT)
≤ 2.5 x ULN; Alkaline phosphatase <2.5 x ULN

- Disease free of prior malignancies for ≥ 5 years with exception of currently treated
basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix
or breast

- All study participants must be registered into the mandatory RevAssist® program, and
be willing and able to comply with the requirements of RevAssist®.

- Females of childbearing potential (FCBP)† must have a negative serum or urine
pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days and again
within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be
filled within 7 days) and must either commit to continued abstinence from
heterosexual intercourse or begin TWO acceptable methods of birth control, one highly
effective method and one additional effective method AT THE SAME TIME, at least 28
days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy
testing. Men must agree to use a latex condom during sexual contact with a FCBP even
if they have had a successful vasectomy.

- Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients
intolerant to acetylsalicylic acid (ASA) may use warfarin or low molecular weight

Exclusion Criteria:

- Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from signing the informed consent form

- Pregnant or breast feeding females. (Lactating females must agree not to breast feed
while taking lenalidomide).

- Any condition, including the presence of laboratory abnormalities, which places the
patient at unacceptable risk if he/she were to participate in the study or confounds
the ability to interpret data from the study

- Evidence of laboratory Tumor Lysis Syndrome (TLS) by Cairo-Bishop Definition.
Patients may be enrolled upon correction of electrolyte abnormalities.

- Use of any other experimental drug or therapy within 28 days of baseline

- Known hypersensitivity to thalidomide

- The development of erythema nodosum if characterized by a desquamating rash while
taking thalidomide or similar drugs.

- Any prior use of lenalidomide

- Concurrent use of other anti-cancer agents or treatments

- Known seropositive for or active viral infection with human immunodeficiency virus

- Positive serology for hepatitis B (HB) defined as a positive test for HBsAg. In
addition, if negative for HBsAg but HBcAb positive and HBsAb negative, a HB DNA test
will be performed and if positive the patient will be excluded. Note: If HBcAb
positive and HBsAb positive, which is indicative of a past infection, the patient can
be included. Patients who are seropositive because of hepatitis B virus vaccine are

- Positive serology for hepatitis C (HC) defined as a positive test for hepatitis C
antibody (HCAb), in which case reflexively perform a HC recombinant immunoblot assay
(RIBA) on the same sample to confirm the result

- Patients 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) are ineligible.

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

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

- Clinically significant cardiac disease including unstable angina, acute myocardial
infarction within 6 months prior to randomization, congestive heart failure [New York
Heart Association (NYHA) III-IV], and arrhythmia unless controlled by therapy, with
the exception of extra systoles or minor conduction abnormalities

- Significant concurrent, uncontrolled medical condition 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 patient

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Participants With Complete Response (CR)

Outcome Description:

The primary endpoint for this trial is the combined complete and partial response rate to the protocol therapy at 3 months, which is also the end of Cycle 3. The objective response (CR+PR) rate will be summarized using both a point estimate and its exact confidence interval based on the binomial distribution.

Outcome Time Frame:

3 Months

Safety Issue:


Principal Investigator

Celeste Bello, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

January 2012

Completion Date:

February 2016

Related Keywords:

  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
  • leukemia
  • lymphoma
  • consolidative therapy
  • combination regimen
  • CLL
  • SLL
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Lymphoma



H. Lee Moffitt Cancer Center and Research InstituteTampa, Florida  33612