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

NCT01497496 | Completed Phase 2 Results DMC

• 3 other identifiers: MCC-16631COMB157AUS08TRV-CLL-PI-0560
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Keywords

leukemia; lymphoma; consolidative therapy; combination regimen; Chronic Lymphocytic Leukemia (CLL); Small Lymphocytic Lymphoma (SLL)

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR at 3 months. Assessment for response will be made following the National Cancer Institute Working Group (NCIWG) 2008 Chronic Lymphocytic Leukemia (CLL) criteria for response. Objective response = Complete Response (disappearance of all target lesions) + Partial Response (\>=30% decrease in the sum of the longest diameter of target lesions) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0)

  3 Months

Secondary Outcomes (2)

• Rate of Progression-free Survival (PFS)

  36 Months

• Rate of Overall Survival (OS)

  36 Months

Study Arms (1)

Immunotherapy

EXPERIMENTAL

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); Drug: Ofatumumab; Drug: Lenalidomide

Interventions

High Dose Methylprednisolone (HDMP) DRUG

1000 mg/m\^2 on Cycle 1: Day 1, 8, 15, 22; Cycle 2: Day 1, 15; Cycle 3: Day 1, 15

Also known as: HDMP, corticosteroid

Immunotherapy

Ofatumumab DRUG

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

Also known as: Arzerra®

Immunotherapy

Lenalidomide DRUG

The lenalidomide treatment will start with cycle 4. 5-10 mg pd Days 1-28 as per Creatinine Clearance (CrCl)

Also known as: Revlimid®, IMiD® compound

Immunotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Understand and voluntarily sign an informed consent form
• Able to adhere to the study visit schedule and other protocol requirements
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Novartis: collaborator
• Celgene Corporation: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia; Lymphoma

Interventions

Methylprednisolone; Adrenal Cortex Hormones; ofatumumab; Lenalidomide

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Celeste Bello, MD
• Organization: Moffitt Cancer Center

Celeste.Bello@moffitt.org

813-745-8623

Study Officials

• Celeste Bello, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2011
• First Posted: December 22, 2011
• Study Start: January 26, 2012
• Primary Completion: September 25, 2019
• Study Completion: March 20, 2020
• Last Updated: April 27, 2021
• Results First Posted: November 4, 2020

Record last verified: 2021-04

Locations

US (1)