Protocol GELLC-7: Ibrutinib Followed by Ibrutinib Consolidation in Combination With Ofatumumab

NCT03280160 | Unknown Phase 2

• 1 other identifier: GELLC-7
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 20

Brief Summary

Based on the promising results obtained with ibrutinib as single agent, the results obtained with ibrutinib in combination with ofatumumab in a previous phase I/IIb study (Jaglowski 2015), and since data from in vitro studies do not support a synergistic effect of the combination of ibrutinib and anti-CD20 mAbs, we propose a chemotherapy-free combined strategy based on ibrutinib monotherapy as front line treatment for patients with CLL, with the addition of a consolidation phase with ofatumumab in patients not attaining CR under ibrutinib in order to improve the quality of their response. Since median time to CR with ibrutinib was nearly 12 months, patients will be evaluated at this time point, and those patients not in CR will add consolidated treatment with Ofatumumab. Thus, this multi-center, non-randomized phase 2 study is designed to evaluate the efficacy and safety of ibrutinib alone or in combination with Ofatumumab in patients no attaining CR under ibrutinib as front-line therapy for patients with chronic lymphocytic leukemia.

Conditions

Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Efficacy in terms of response rate

  To determine the complete response rate obtained with the combination of Ibrutinib and ofatumumab

  18 months

Interventions

Ibrutinib 140 MG Oral Capsule [Imbruvica] DRUG

Ibrutinib will be administered orally 420 mg (3 x 140 mg capsules) once daily on a continuous schedule on an outpatient basis until disease progression or unacceptable toxicity. After 12 cycles of ibrutinib, patients that do not achieve a complete response (CR) will be treated with the combination of ibrutinib and ofatumumab. Patients in CR after 12 cycles of ibrutinib will continue with ibrutinib alone. Ofatumumab will be administered by IV infusion, 300mg on Day 1 and 1,000 mg on Day 8 of cycle 13, followed by 5 monthly infusions of 1,000 mg (Day 1 of subsequent 28-day cycles for cycles C14, C15, C16, C17, and C18). A treatment cycle will be defined as lasting 28 days

Also known as: Ofatumumab

Eligibility Criteria

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

You may qualify if:

• Adult patients with previously untreated CLL or SLL defined following IWCLL criteria (Hallek, 2008).
• Must understand and voluntarily sign an informed consent form.
• Age ≥ 18 years at the time of signing the informed consent form and must be able to adhere to the study visit schedule and other protocol requirements.
• Must have a documented diagnosis of CLL or SLL \[IWCLL guidelines for diagnosis and treatment of CLL (Hallek, 2008)\] meeting at least one of the following criteria:
• Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia.
• Massive (i.e. \> 6 cm below the left costal margin) or progressive or symptomatic splenomegaly.
• Massive nodes (i.e. \> 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy.
• Progressive lymphocytosis with an increase of \> 50% over a 2-month period, or lymphocyte doubling time (LDT) of less than 6 months.
• A minimum of any one of the following disease-related symptoms: unintentional weight loss ≥ 10% within the previous 6 months, significant fatigue (i.e., ECOG PS 2; cannot work or unable to perform usual activities), fevers of greater than 38.0° C or 100.5F for 2 or more weeks without other evidence of infection, or night sweats for more than 1 month without evidence of infection
• Physically fit patients defined as CIRS \< 6 (CIRS Scale, Appendix E).
• Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of ≤2.
• All sexually active subjects with the capacity to reproduce (male and female) must use high-efficacy contraceptive methods during the course of the study. These restrictions apply for 12 months after the last dose of ofatumumab or 3 months after the last dose of ibrutinib, whichever happens later. High-efficacy contraceptive methods include:
• Total abstinence when consistent with the subject's typical and preferred lifestyle (periodic abstinence \[e.g. calendar methods, ovulation, symptothermal and post-ovulation methods\] and the withdrawal method are not acceptable contraceptive methods).
• Female sterilisation defined as surgical hysterectomy, bilateral oophorectomy, or tubal ligation at least six weeks prior to the study treatment (a simple oophorectomy does not meet the definition of female sterilisation).
• Male sterilisation (at least six months before screening). A man who has undergone a vasectomy must be the only partner who is a study subject.

You may not qualify if:

• Prior treatment for CLL or SLL.
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent form.
• Systemic infection that has not resolved prior to initiating study treatment in spite of adequate anti-infective therapy.
• Pregnant or lactating females.
• Participation in any clinical study or having taken any investigational therapy within 28 days prior to initiating study therapy.
• Central nervous system (CNS) involvement as documented by spinal fluid cytology or imaging.
• Prior history of malignancies, other than CLL, unless the patient has been free of the disease for ≥ 3 years.
• Exceptions include the following:
• Basal cell carcinoma of the skin Squamous cell carcinoma of the skin Carcinoma in situ of the cervix Carcinoma in situ of the breast Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)
• Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and/or Hepatitis C Virus (HCV) infection.
• Any of the following laboratory abnormalities:
• Serum creatinine ≥ 2 x ULN or estimated Glomerular Filtration Rate (Cockroft-GaultAppendix C) ≤ 40 mL/min/1.73m2 Absolute neutrophil count (ANC) \< 1.0 X 109/L, unless secondary to bone marrow involvement by CLL.
• Platelet count \<100,000/mm3 or \<50,000/mm3 if bone marrow involvement independent of transfusion support in either situation Serum aspartate aminotransferase (AST)/serum glutamic-oxaloacetictransaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) \>3 x upper limit of normal (ULN).
• Serum total bilirubin \> 1.5 x ULN, except in cases of Gilbert's syndrome.
• Presence of autoimmune haemolytic anemia or autoimmune thrombocytopenia.

Sponsors & Collaborators

• PETHEMA Foundation: lead

Study Sites (20)

Hospital Son Espases (Son Dureta)

Palma de Mallorca, Balearic Islands, 07010, Spain

Location

Hospital de Badalona Germans Trias i Pujol

Badalona, Spain

Location

Hospital Clínic de Barcelona

Barcelona, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, Spain

Location

ICO Hospitalet - Hospital Duran i Reynals

Barcelona, Spain

Location

Hospital Reina Sofía de Córdoba

Córdoba, Spain

Location

Fundación Jiménez Díaz

Madrid, Spain

Location

Hospital Infanta Leonor

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario de la Princesa

Madrid, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Hospital Universitario Puerta de Hierro

Madrid, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, Spain

Location

Hospital Universitario de Salamanca

Salamanca, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, Spain

Location

Hospital Nuestra Señora de Valme

Seville, Spain

Location

Hospital Virgen de la Salud de Toledo

Toledo, Spain

Location

Hospital Clínico de Valencia

Valencia, Spain

Location

Hospital La Fe de Valencia

Valencia, Spain

Location

Related Links

• PETHEMA Foundation

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

ibrutinib; ofatumumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; 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

Study Design

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

Study Record Dates

• First Submitted: September 9, 2017
• First Posted: September 12, 2017
• Study Start: September 7, 2017
• Primary Completion: July 13, 2018
• Study Completion: September 1, 2022
• Last Updated: September 16, 2022

Record last verified: 2022-09

Locations

ES (20)