Lenalidomide and Obinutuzumab for Previously Untreated CLL

A Phase 2 Clinical Trial To Evaluate Lenalidomide And Obinutuzumab For The Treatment Of Patients With Not Previously Treated Chronic Lymphocytic Leukemia

This is phase 1/2 study for patients with CLL or (SLL) who have not been previously treated. This study will evaluate whether obinutuzumab and lenalidomide is safe and tolerable in this setting and induce complete clinical responses.

Study Overview

• Status: Withdrawn
• Conditions: Chronic Lymphocytic Leukemia
• Intervention / Treatment: Drug: Lenalidomide; Drug: Obinutuzumab

Detailed Description

This is phase 1/2 study for patients with CLL or (SLL) who have not been previously treated. The primary endpoint is to determine safety and tolerability of the regimen and determine complete response (CR) to therapy. The secondary endpoints will assess the impact of treatment on progression free and overall survival

Eligible patients will receive obinutuzumab for 6 x 28 day cycles. Patients will also receive lenalidomide orally once daily on days 8-28 of each 28 day cycles. The starting dose for all patients is 5 mg PO daily. At the start of each cycle, there is intra-patient dose-escalation to a maximum of 25mg daily, as tolerated.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• Main Inclusion Criteria:

  1. Clinical and phenotypic verification of B cell CLL or SLL and measurable disease.
  2. Prior therapy: no prior CLL therapy.
  3. Patients must have progressive disease based on 2008 iwCLL definition with one of the following:
• Symptomatic or progressive splenomegaly
• Symptomatic lymph nodes, nodal clusters, or progressive lymphadenopathy
• Progressive anemia (hemoglobin ≤ 11 g/dL)
• Progressive thrombocytopenia (platelets ≤ 100 x 109/L)
• Weight loss > 10% body weight over the preceding 6 month period
• Fatigue attributable to CLL
• Fever or night sweats for > 2 weeks without evidence of infection
• Progressive lymphocytosis with an increase of > 50% over a 2-month period or an anticipated doubling time of less than 6 months.
• Able to take aspirin (81mg or 325mg) daily, warfarin, low molecular weight heparin, or equivalent anticoagulation as prophylactic medication.
• All study participants must be registered into the mandatory Revlimid 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 prior to and again within 24 hours prior to starting Revlimid and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control.
• Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS program.
• ECOG performance status of 0-2.
• Adequate hematologic function
• Adequate renal function
• Adequate hepatic function

Exclusion Criteria:

• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies. Women for child-bearing age must obtain a pregnancy test and pregnant or breast feeding females are excluded.
• Known hypersensitivity to thalidomide or lenalidomide (if applicable), including development of erythema nodosum or a desquamating rash while taking thalidomide or similar drugs.
• Deep vein thrombosis or superficial thrombophlebitis of any cause on current anticoagulation therapy at the time of screening.
• Patients who are currently receiving another investigational agent are excluded.
• Current infection requiring parenteral antibiotics.
• Known seropositive for or active viral infection with human immunodeficiency virus (HIV); or known active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) based on detectable viral load. Patients who are seropositive because of hepatitis B virus vaccine or passive immunization by intravenous immunoglobulin (IVIG) are eligible.
• Active malignancy within the previous 2 years (other than completely resected non-melanoma skin cancer or carcinoma in situ).
• Known central nervous system (CNS) involvement by malignancy.
• Untreated autoimmunity such as autoimmune hemolytic anemia, or immune thrombocytopenia.
• Insufficient recovery from surgical-related trauma or wound healing.
• Impaired cardiac function

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Lenalidomide-Obinutuzumab; All patients receive the combination of lenalidomide and obinutuzumab. There is no randomization or comparator arm.

Drug: Lenalidomide; Lenalidomide is administered orally once daily on Days 8-28 of each 28 day cycle. The starting dose for all patients is 5 mg PO daily. At the start of each cycle, there is intra-patient dose-escalation to a maximum of 25mg daily, as tolerated. The study consists of a 6 month treatment period with obinutuzumab and lenalidomide, and an indefinite period of treatment with lenalidomide for as long as it is helpful and tolerated by subject.; Other Names: Revlimid; Drug: Obinutuzumab; Obinutuzumab is administered as follows: Cycle 1: 100mg IV on day 1, 900 mg IV on day 2, 1000mg day 8, 1000 mg on day 15. Cycles 2-6: 1000mg IV on day 1.; Other Names: Gazyva

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of dose limiting toxicity	For phase 1 portion of study	1 year
Complete Response Rate	For phase 2 portion of study: iwCLL 2008 defined complete response rate	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with adverse events associated with lenalidomide-obinutuzumab		2 years
Progression free survival rate	Progression free survival rate at completion of combination therapy, total progression free survival, and overall survival determined by International Working Group in CLL (iwCLL) criteria	2 years
Overall response rate	Overall response rate (Complete response + partial response) and stable disease rate (also based on 2008 iwCLL guidelines), also at the time of primary endpoint response assessment.	2 years

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Collaborators: Genentech, Inc.; Celgene Corporation
• Investigators: Principal Investigator: Michael Choi, MD, UC San Diego Moores Cancer Center

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2018
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: February 13, 2015
• First Submitted That Met QC Criteria: February 24, 2015
• First Posted (Estimate): February 25, 2015

Study Record Updates

• Last Update Posted (Actual): February 23, 2018
• Last Update Submitted That Met QC Criteria: February 21, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: lenalidomide; cancer; CLL; obinutuzumab
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide; Obinutuzumab
• Other Study ID Numbers: 150342/161104

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No