- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01496976
Ofatumumab, High Dose Methylprednisolone, Ofatumumab and Lenalidomide Consolidative Therapy for Untreated CLL/SLL
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
Study Overview
Status
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
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Florida
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Tampa, Florida, United States, 33612
- H. Lee Moffitt Cancer Center and Research Institute
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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 REMS® program, and be willing and able to comply with the requirements of REMS®.
- 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 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 (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. Consult with a physician experienced in care & management of subjects with hepatitis B to manage/treat subjects who are anti-HBc positive.
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Immunotherapy
Combination Regimen Followed by Consolidative Therapy: Ofatumumab/High Dose Methylprednisolone (HDMP) plus Ofatumumab/Lenalidomide
|
HDMP will be administered at 1 gm/m^2 IV over 90 minutes daily with ofatumumab infusions 1-8.
Other Names:
Ofatumumab infusion will be administered immediately after HDMP.
Other Names:
The Lenalidomide Starting Dose (Cycle 4) Based on Renal Function Prior to Cycle 4 of Treatment.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Complete Response (CR)
Time Frame: 3 Months
|
Number of participants with complete response, the disappearance of all signs of cancer in response to treatment.
|
3 Months
|
Number of Participants With Partial Response (PR)
Time Frame: 3 Months
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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.
|
3 Months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of Progression/Relapse Free Survival (PFS)
Time Frame: Up to 56 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.
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Up to 56 months
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Number of Participants With Overall Survival (OS)
Time Frame: 36 Months
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Overall survival will be summarized with the Kaplan-Meier curve.
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36 Months
|
Collaborators and Investigators
Investigators
- Principal Investigator: Celeste Bello, M.D., H. Lee Moffitt Cancer Center and Research Institute
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Disease Attributes
- Leukemia, Lymphoid
- Leukemia
- Leukemia, B-Cell
- Chronic Disease
- Leukemia, Lymphocytic, Chronic, B-Cell
- Physiological Effects of Drugs
- Autonomic Agents
- Peripheral Nervous System Agents
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Immunologic Factors
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Neuroprotective Agents
- Protective Agents
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Prednisolone
- Methylprednisolone Acetate
- Methylprednisolone
- Methylprednisolone Hemisuccinate
- Prednisolone acetate
- Prednisolone hemisuccinate
- Prednisolone phosphate
- Lenalidomide
- Ofatumumab
Other Study ID Numbers
- MCC-16622
- COMB157BUS21T (Other Grant/Funding Number: Novartis)
- RV-CLL-PI-0560 (Other Grant/Funding Number: Celgene Corp.)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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