Ofatumumab, High Dose Methylprednisolone, Ofatumumab and Lenalidomide Consolidative Therapy for Untreated CLL/SLL

• ClinicalTrials.gov Identifier: NCT01496976
• Recruitment Status: Active, not recruiting
• First Posted: December 22, 2011
• Last Update Posted: February 7, 2020
• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborators: Novartis; Celgene Corporation
• Information provided by (Responsible Party): H. Lee Moffitt Cancer Center and Research Institute

Tracking Information

• First Submitted Date: December 16, 2011
• First Posted Date: December 22, 2011
• Last Update Posted Date: February 7, 2020
• Actual Study Start Date: March 30, 2012
• Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 21, 2011)

• Number of Participants With Complete Response (CR) [ Time Frame: 3 Months ]
  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.
• Number of Participants With Partial Response (PR) [ Time Frame: 3 Months ]
  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.

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT01496976 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: December 21, 2011)

• Number of Participants With Progression/Relapse 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. Confidence intervals for the median and survival rates at different time points will be constructed if needed.
• Number of Participants With Overall Survival (OS) [ Time Frame: 36 Months ]
  Overall survival will be summarized with the Kaplan-Meier curve.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Ofatumumab, High Dose Methylprednisolone, Ofatumumab and Lenalidomide Consolidative Therapy for Untreated CLL/SLL
• Official Title: 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
• Brief Summary: The main purpose of this study is to see if ofatumumab with methylprednisolone followed by additional treatment with ofatumumab and lenalidomide can help people with Chronic Lymphocytic Leukemia (CLL) get rid of their CLL 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.

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: Interventional
• Study Phase: Phase 2
• Study Design: Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Chronic Lymphocytic Leukemia
• Small Lymphocytic Lymphoma

Intervention

• Drug: High Dose Methylprednisolone (HDMP)
  HDMP will be administered at 1 gm/m^2 IV over 90 minutes daily with ofatumumab infusions 1-8.
  Other Name: HDMP
• Drug: Ofatumumab
  Ofatumumab infusion will be administered immediately after HDMP.
  Other Name: Arzerra®
• Drug: Lenalidomide
  The Lenalidomide Starting Dose (Cycle 4) Based on Renal Function Prior to Cycle 4 of Treatment.
  Other Names:

  • Revlimid®
  • IMiD® compound

Study Arms

Experimental: Immunotherapy

Combination Regimen Followed by Consolidative Therapy: Ofatumumab/High Dose Methylprednisolone (HDMP) plus Ofatumumab/Lenalidomide

Interventions:

• Drug: High Dose Methylprednisolone (HDMP)
• Drug: Ofatumumab
• Drug: Lenalidomide

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: December 21, 2011): 45
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2020
• Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01496976
• Other Study ID Numbers: MCC-16622; COMB157BUS21T ( Other Grant/Funding Number: Novartis ); RV-CLL-PI-0560 ( Other Grant/Funding Number: Celgene Corp. )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• Study Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Collaborators

• Novartis
• Celgene Corporation

Investigators

• Principal Investigator: Celeste Bello, M.D.; H. Lee Moffitt Cancer Center and Research Institute

• PRS Account: H. Lee Moffitt Cancer Center and Research Institute
• Verification Date: February 2020