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Ofatumumab/Methylprednisolone and Ofatumumab/Lenalidomide for Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

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. Identifier: NCT01497496
Recruitment Status : Active, not recruiting
First Posted : December 22, 2011
Last Update Posted : June 4, 2020
Celgene Corporation
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Brief Summary:
The main purpose of this study is to see if the combination of ofatumumab with high dose methylprednisolone followed by additional treatment with ofatumumab and lenalidomide can help people with relapsed or refractory CLL/SLL get rid of their CLL/SLL for a long period of time. Researchers also want to find out if the combination of ofatumumab with methylprednisolone followed by additional treatment with ofatumumab and lenalidomide is safe and tolerable.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Drug: High Dose Methylprednisolone (HDMP) Drug: Ofatumumab Drug: Lenalidomide Phase 2

Detailed Description:

This is a phase II, single institution, and non-randomized study of patients with relapsed or refractory 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 (after the end of cycle 3) to the protocol therapy. Investigators anticipate this trial will have a complete response and partial response (CR+PR) rate of at least 55%.

A two-stage design is employed for this trial. The null/unacceptable CR+PR response rate is ≤35% while the anticipated true response rate to the protocol treatment is at least 55% for each disease cohort. At the first stage, 25 patients will be accrued to the trial. If 9 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 (≤35%). Otherwise, if more than 9 patients respond during the first stage, an additional 31 patients will be enrolled to this trial during stage 2 for a total of 56 patients. If 25 or fewer of these 56 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 25 patients out of the 56 enrolled patients respond, the protocol treatment will be considered promising. If the true response rate is ≤35%, the probability of ending the trial at stage 1 is 0.63. If, however, the true response rate is at least 55%, then the probability of ending the trial at stage 1 is only 0.04. This two-stage design has an overall alpha level of 0.047 and a power of 0.90.

For the purpose of interim analysis at the end of stage 1, the objective response will be measured by the end of 3 months (or end of cycle 3) from the start of the protocol treatment prior to the initiation of the combination of ofatumumab with lenalidomide. The accrual will not be suspended while waiting for the results of the interim analysis unless the observed objective response rate among those patients whose objective response data are available is below 30%.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Ofatumumab in Combination With High Dose Methylprednisolone Followed by Ofatumumab and Lenalidomide Consolidative Therapy for the Treatment of Relapsed or Refractory CLL/SLL The HiLOG Trial
Study Start Date : January 20, 2012
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2021

Arm Intervention/treatment
Experimental: Immunotherapy
Combination regimen consisting of high dose methylprednisolone combined with ofatumumab, followed by consolidative therapy with lenalidomide in combination with ofatumumab.
Drug: High Dose Methylprednisolone (HDMP)
1000 mg/m^2 on Cycle 1: Day 1, 8, 15, 22; Cycle 2: Day 1, 15; Cycle 3: Day 1, 15
Other Names:
  • HDMP
  • corticosteroid

Drug: Ofatumumab
Ofatumumab infusion will be administered immediately after HDMP. 300 mg on Cycle 1 Day 1. 2000 mg on Cycle 1: Day 8, 15, 22; Cycle 2: Day 1, 15; Cycle 3: Day 1, 15; Cycle 6: Day 1; Cycle 8: Day 1; Cycle 10: Day 1: Cycle 12: Day 1
Other Name: Arzerra®

Drug: Lenalidomide
The lenalidomide treatment will start with cycle 4. 5-10 mg pd Days 1-28 as per Creatinine Clearance (CrCl)
Other Names:
  • Revlimid®
  • IMiD® compound

Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: 3 Months ]
    Assessment for response will be made following the National Cancer Institute Working Group (NCIWG) 2008 Chronic Lymphocytic Leukemia (CLL) criteria for response. The primary endpoint for this trial is the combined complete response (CR) and partial response (PR) rate to the protocol therapy at 3 months, which is the end of Cycle 3.

Secondary Outcome Measures :
  1. Rate of Progression-free Survival (PFS) [ Time Frame: 36 Months ]
    Progression-free survival (PFS), defined as the time from study entry to disease progression, relapse or death due to any cause, whichever is earlier, will be summarized with the Kaplan-Meier curve. Progressive Disease (PD) defined according to NCIWG 2008 CLL Criteria for Response.

  2. Rate of Overall Survival (OS) [ Time Frame: 36 Months ]
    Overall Survival Time: Time from initiation of treatment to time of death. Overall survival will be summarized with the Kaplan-Meier curve.

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.

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

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 (BM) lymphocytes ≥ 30%; Or previous confirmed diagnosis of CLL/SLL with less than 5000/μl or less than 30% lymphocytes in BM.
  • Patients are eligible if they have relapsed or refractory CLL/SLL.
  • All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study.
  • 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 heparin)

Exclusion Criteria:

  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient 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 (HIV)
  • 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 eligible.
  • Positive serology for hepatitis C (HC) defined as a positive test for hepatitis C antibodies (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

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 identifier (NCT number): NCT01497496

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United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Celgene Corporation
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Principal Investigator: Celeste Bello, M.D. H. Lee Moffitt Cancer Center and Research Institute
Additional Information:
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Responsible Party: H. Lee Moffitt Cancer Center and Research Institute Identifier: NCT01497496    
Other Study ID Numbers: MCC-16631
COMB157AUS08T ( Other Grant/Funding Number: Novartis )
RV-CLL-PI-0560 ( Other Grant/Funding Number: Celgene Corp. )
First Posted: December 22, 2011    Key Record Dates
Last Update Posted: June 4, 2020
Last Verified: January 2020
Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
consolidative therapy
combination regimen
Chronic Lymphocytic Leukemia (CLL)
Small Lymphocytic Lymphoma (SLL)
Additional relevant MeSH terms:
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Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Anti-Inflammatory Agents
Autonomic Agents