Clinical Trials /

Ofatumumab & Ibrutinib + Allogeneic Bone Marrow Transplant or Consolidation in High Risk Chronic Lymphocytic Leukemia

NCT02388048

Description:

A clinical study to evaluate a treatment with two drugs, named Ofatumumab and Ibrutinib, in patients with lymphoblastic acute leukemia who have been already treated with other therapies.

Related Conditions:
  • Chronic Lymphocytic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ofatumumab & Ibrutinib + Allogeneic Bone Marrow Transplant or Consolidation in High Risk Chronic Lymphocytic Leukemia
  • Official Title: A Phase II Study of the Combination of Ofatumumab and Ibrutinib Followed by Allogeneic Bone Marrow Transplant or Consolidation for Pretreated High Risk Patients With Chronic Lymphocytic Leukemia

Clinical Trial IDs

  • ORG STUDY ID: LLC1215
  • SECONDARY ID: 2015-000684-13
  • NCT ID: NCT02388048

Conditions

  • Leukemia, Lymphoblastic, Chronic

Interventions

DrugSynonymsArms
Ibrutinib + ofatumumabIbrutinib + Ofatumumab

Purpose

A clinical study to evaluate a treatment with two drugs, named Ofatumumab and Ibrutinib, in patients with lymphoblastic acute leukemia who have been already treated with other therapies.

Detailed Description

      This is a phase II multicenter, non-comparative, open label study for high risk previously
      treated patients with CLL, requiring therapy, aimed at evaluating the efficacy of the
      Ofatumumab and Ibrutinib combination.
    

Trial Arms

NameTypeDescriptionInterventions
Ibrutinib + OfatumumabExperimentalIBRUTINIB 420 mg PO daily in 28-day cycles for a total of 7 cycles (28 weeks). OFATUMUMAB 300 mg on day 1 of cycle 2 of Ibrutinib, followed by 2000 mg on D8, 15, 22 of cycle 2, D1, 8, 15, 22 of cycle 3, and Day 1 of cycle 4-7. After induction treatment patients with HLA identical sibling or fully matched MUD donor will be addressed to reduced intensity allogeneic bone marrow transplant, while patients without a suitable donor or who refuse the transplant procedure will receive maintenance treatment by BTK inhibitor (IBRUTINIB 420 mg PO daily in 28-day cycles). Treatment will continue until disease progression or unacceptable toxicity.
  • Ibrutinib + ofatumumab

Eligibility Criteria

        Inclusion Criteria:

          1. Male or female, age 18 years or until 65 years;

          2. Confirmation of B-CLL previously treated with no more than 1 previous line of
             treatment .

          3. Risk patients with CLL defined as follows:

               -  treated patients showing 17p deletion in >20% of the cells by FISH, or TP53
                  mutation or,

               -  resistant (SD/PD) to fludarabine containing combination therapy or relapse within
                  12 months from a fludarabine-containing combination therapy.

          4. Active disease meeting at least 1 of the following IWCLL criteria for requiring
             treatment:

               -  Evidence of progressive marrow failure as manifested by the development of, or
                  worsening of anemia (Hb< 10 g/dL) and/or thrombocytopenia (platelets <
                  100,000/mL).

               -  Massive (≥ 6 cm below the left costal margin), progressive, or symptomatic
                  splenomegaly.

               -  Massive nodes (at least 10 cm longest diameter), or progressive or symptomatic
                  lymphadenopathy.

               -  Progressive lymphocytosis with an increase of more than 50% over a 2-month period
                  or a lymphocyte doubling time (LDT) of < 6 months.

               -  Autoimmune hemolytic anemia and/or immune thrombocytopenia that is poorly
                  responsive to corticosteroids or other standard therapy.

               -  One or more disease-related symptoms:

               -  unintentional weight loss > 10% within 6 months prior to screening;

               -  significant fatigue (inability to work or perform usual activities);

               -  fevers >38.0°C for 2 or more weeks prior to screening;

               -  night sweats for more than 1 month prior to screening.

          5. Stage B or C of CLL according to Binet staging system;

          6. Stage A disease fitting the criteria for treatment according to the IWCLL-NCI criteria
             (2008) are also included.

          7. WHO performance status 0-II.

          8. Life expectancy ≥ 6 months.

          9. Hematology values must be within the following limits:

               -  Absolute neutrophil count (ANC) ≥ 750/mm3 independent of growth factor support;

               -  Platelets ≥100,000/mm3 or ≥ 30.000/mm3 if bone marrow involvement independent of
                  transfusion support in either situation.

         10. Biochemical values within the following limits:

               -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x upper
                  limit of normal (ULN).

               -  Total bilirubin ≤ 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or
                  of non-hepatic origin.

               -  Serum creatinine ≤ 2 x ULN or estimated Glomerular Filtration Rate (Cockroft
                  Gault) ≥ 30 mL/min/1.73m2.

         11. Women of childbearing potential and men who are sexually active must be practicing a
             highly effective method of birth control during and after the study For females, these
             restrictions apply for 1 month after the last dose of ibrutinib and for 12 months
             after the last dose of Ofatumumab. For males, these restrictions apply for 3 months
             after the last dose of ibrutinib. Men must agree to not donate sperm during and after
             the study.

         12. Women of childbearing potential must have a negative serum (beta-human chorionic
             gonadotropin [β-hCG]) or urine pregnancy test at Screening. Women who are pregnant or
             breastfeeding are ineligible for this study.

         13. Sign an informed consent document indicating that they understand the purpose of and
             procedures required for the study, including biomarkers, and are willing to
             participate in the study.

        Exclusion Criteria:

          1. Major surgery within 3 weeks before registration.

          2. Known central nervous system lymphoma.

          3. History of stroke or intracranial hemorrhage within 6 months prior to registration.

          4. Requires anticoagulation with warfarin or equivalent vitamin K antagonists (eg,
             phenprocoumon).

          5. Clinically significant cardiovascular disease such as uncontrolled or symptomatic
             arrhythmias, congestive heart failure, or myocardial infarction within 6 months of
             Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by
             the New York Heart Association Functional Classification.

          6. Vaccinated with live, attenuated vaccines within 4 weeks of registration.

          7. Known history of human immunodeficiency virus (HIV) or active Hepatitis C Virus or
             active Hepatitis B Virus infection or any uncontrolled active systemic infection
             requiring intravenous (IV) antibiotics.

          8. Any life-threatening illness, medical condition, or organ system dysfunction which, in
             the investigator's opinion, could compromise the subject's safety, interfere with the
             absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue
             risk.

          9. Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In
             addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a
             HBDNA test will be performed and if positive the subject will be excluded. ***see
             attached monitoring criteria for HBcAb+ and HBV DNA negative subjects.

         10. Other past or current malignancy. Subjects who have been free of malignancy for at
             least 5 years, or have a history of completely resected non-melanoma skin cancer, or
             successfully treated in situ carcinoma are eligible.

         11. Requirement for treatment with a strong CYP3A4/5 and/or CYP2D6 inhibitor.

         12. 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.

         13. Inability to swallow capsules or tablets, or disease significantly affecting
             gastrointestinal function and/or inhibiting small intestine absorption.

         14. 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.

         15. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura.

         16. Central nervous system involvement with CLL.

         17. Subjects 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).

         18. Treatment with any known non-marketed drug substance or experimental therapy within 5
             terminal half lives or 4 weeks prior to enrollment, whichever is longer, or currently
             participating in any other interventional clinical study.

         19. Prior treatment with anti-CD20 monoclonal antibody or alemtuzumab within 3 months
             prior to the start of therapy.

         20. History of significant cerebrovascular disease in the past 6 months or ongoing event
             with active symptoms or sequelae.

               -  If HBV DNA is negative, subject may be included but must undergo at least every 2
                  month HBV DNA PCR testing from the start of treatment during the treatment
                  course. Prophylactic antiviral therapy may be initiated at the discretion of the
                  investigator.
      
Maximum Eligible Age:65 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The number of pretreated patients with high risk CLL who achieve a Complete Response (CR) after the induction therapy with Ibrutinib plus Ofatumumab.
Time Frame:After 6.5 years from treatment start
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Number of patients in Complete Response (CR)/Partial Response (PR)
Time Frame:After 28 weeks from treatment start
Safety Issue:
Description:Overall response rate at the end of induction therapy.
Measure:Number of patients without progression of the disease.
Time Frame:At 60 months from treatment start
Safety Issue:
Description:Progression-free survival
Measure:Number of patients alive
Time Frame:At 60 months from treatment start
Safety Issue:
Description:Overall survival
Measure:Number of patients without events
Time Frame:At 60 months from treatment start
Safety Issue:
Description:Event-free survival
Measure:Number of Minimal Residual Disease-negative Complete Responses
Time Frame:At 28 weeks from treatment start
Safety Issue:
Description:6. To estimate Minimal Residual Disease (MRD) in terms of rate of MRD-negative CRs at the end of induction therapy and after SCT or Ibrutinib maintenance therapy for patients in CR
Measure:Number of adverse events
Time Frame:At 6.5 years after treatment start
Safety Issue:
Description:7. Safety profile and tolerability of the combination of Ofatumumab and Ibrutinib and the ibrutinib as maintenance in terms of type, frequency, severity and relationship of adverse events (AEs).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Gruppo Italiano Malattie EMatologiche dell'Adulto

Trial Keywords

  • Leukemia
  • Chronic
  • High-risk
  • ofatumumab
  • ibrutinib
  • Lymphoblastic

Last Updated

July 31, 2018