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Leukemia, Lymphoblastic, ChronicPhase 2NCT02388048

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

A Phase 2 study testing Ibrutinib + ofatumumab in people with Leukemia, Lymphoblastic, Chronic, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 35 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Leukemia, Lymphoblastic, Chronic
What is being tested?
Ibrutinib + ofatumumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
35 sitesItaly
Study dates
Oct 2015to 3 Apr 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female, age 18 years or until 65 years;
  • Confirmation of B-CLL previously treated with no more than 1 previous line of treatment .
  • 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.
  • Active disease meeting at least 1 of the following IWCLL criteria for requiring treatment:
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  • 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.
  • Stage B or C of CLL according to Binet staging system;
  • Stage A disease fitting the criteria for treatment according to the IWCLL-NCI criteria (2008) are also included.
  • WHO performance status 0-II.
  • Life expectancy ≥ 6 months.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

Who cannot join

  • Major surgery within 3 weeks before registration.
  • Known central nervous system lymphoma.
  • History of stroke or intracranial hemorrhage within 6 months prior to registration.
  • Requires anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon).
  • 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.
  • Vaccinated with live, attenuated vaccines within 4 weeks of registration.
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  • 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.
  • 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.
  • 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.
  • 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.
  • Requirement for treatment with a strong CYP3A4/5 and/or CYP2D6 inhibitor.
  • 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.
  • Inability to swallow capsules or tablets, or disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption.
  • 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.
  • Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura.
  • Central nervous system involvement with CLL.
  • 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).
  • 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.
  • Prior treatment with anti-CD20 monoclonal antibody or alemtuzumab within 3 months prior to the start of therapy.
  • 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.

Trial locations and contacts

35 sites in 1 country.

35 sites in 1 country

Italy35 sites

  • S.O.C. di Ematologia - Azienda Ospedaliera - SS. Antonio e Biagio e Cesare Arrigo

    Alessandria

  • Area Vasta N. 5 Ascoli Piceno - S. Benedetto Del Tronto, Presidio Ospedaliero Av5 Osp. Gen. Prov.Le "C.G.Mazzoni" - Uoc Ematologia

    Ascoli Piceno

  • Nuovo Record Esporta in Excel Stampa Esporta in file di testo Mostra Informazioni Record Multi edit Stato dello studio presso il centro records: 28 Record 1/28 su 28 direzione di ordinamento Centro (CIC) direzione di ordinamento Sperimentatore Pri

    Bologna

  • ASL N.8 - Ospedale "A. Businco" - Struttura Complessa di Ematologia e CTMO

    Cagliari

  • Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"

    Catania

  • Azienda Ospedaliera Pugliese Ciaccio - Presidio Ospedaliero A.Pugliese - Unità Operativa di Ematologia

    Catanzaro

  • Nuovo Record Esporta in Excel Stampa Esporta in file di testo Mostra Informazioni Record Multi edit Stato dello studio presso il centro records: 28 Record 1/28 su 28 direzione di ordinamento Centro (CIC) direzione di ordinamento Sperimentatore Pri

    Cona

  • U.O. Ematologia - P.O. Annunziata - A.O. di Cosenza

    Cosenza

  • Policlinico di Careggi

    Florence

  • IRCCS_AOU San Martino-IST-Ematologia 1-Monoblocco 11°piano- lato ponente

    Genova

  • ASL Le/1 P.O. Vito Fazzi - U.O. di Ematologia ed UTIE

    Lecce

  • Istituto Scientifico Romagnoli per lo Studio e la Cura dei Tumori- IRST

    Meldola

  • Divisione di Ematologia - Azienda Ospedaliera Ospedali Riuniti "Papardo Piemonte" P.O. Papardo

    Messina

  • Aulss 3 Serenissima, Ospedale Dell'Angelo - Mestre - Uo Ematologia

    Mestre

  • Fondazione Irccs "Istituto Nazionale Tumori" - Milano - Sc Ematologia

    Milan

  • Ospedale Niguarda " Ca Granda" - SC Ematologia Blocco SUD, Ponti Est, Scala E, 4° piano

    Milan

  • S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro

    Novara

  • Aou Di Padova - Uo Ematologia

    Padova

  • Sl Salerno, Presidio Ospedaliero Tortora Pagani - Ematologia

    Pagani

  • U.O. di Ematologia con trapianto - Centro di Riferimento Regionale per le coagulopatie rare nel bambino e nell'adulto Dipart. Biomedico di Medicina Interna - A.U. Policlinico "Paolo Giaccone"

    Palermo

  • Cattedra di Ematologia CTMO Università degli Studi di Parma

    Parma

  • Sezione di Ematologia ed Immunologia Clinica - Ospedale S.Maria della Misericordia

    Perugia

  • U.O. Ematologia Clinica - Azienda USL di Pescara

    Pescara

  • Asl Di Piacenza, Ospedale "Guglielmo Da Saliceto" - Ematologia E Centro Trapianti

    Piacenza

  • Unità Operativa Complessa di Ematologia - Arcispedale S. Maria Nuova

    Reggio Emilia

  • Ospedale "Infermi"

    Rimini

  • Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia

    Roma, Provincia, 00141

  • Università Cattolica del Sacro Cuore - Policlinico A. Gemelli

    Roma

  • Università degli Studi - Policlinico di Tor Vergata

    Roma

  • Università Degli Studi Di Roma "Sapienza" - Dipartimento Di Medicina Traslazionale E Di Precisione - U.O.C. Ematologia

    Roma

  • A.O. Santa Maria - Terni S.C Oncoematologia

    Terni

  • A.O. Mauriziano Umberto I

    Torino

  • Dipartimento di Oncologia ed Ematologia S.C. Ematologia 2 A.O. Città della Salute e della Scienza di Torino San Giovanni Battista

    Torino

  • Divisione di Ematologia dell' Università degli Studi di Torino - "Città della Salute e della Scienza di Torino"

    Torino

  • Università degli Studi di Verona - A. O. - Istituti Ospitalieri di Verona- Div. di Ematologia - Policlinico G.B. Rossi

    Verona

Other trials in Italy

About this study

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

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.

Read the 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.

Being tested
Ibrutinib + ofatumumab
Keywords
Leukemia, Chronic, High-risk, ofatumumab, ibrutinib, Lymphoblastic
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Bronchiolitis Obliterans Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ibrutinib + ofatumumabDrug

Study groups in NCT02388048
Study groupRoleWhat they receive
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.
Receives: Drug: Ibrutinib + ofatumumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The number of pretreated patients with high risk CLL who achieve a Complete Response (CR) after the induction therapy with Ibrutinib plus Ofatumumab.

    Measured: After 6.5 years from treatment start

Secondary outcomes (6)

  1. Number of patients in Complete Response (CR)/Partial Response (PR)

    Overall response rate at the end of induction therapy.

    Measured: After 28 weeks from treatment start

  2. Number of patients without progression of the disease.

    Progression-free survival

    Measured: At 60 months from treatment start

  3. Number of patients alive

    Overall survival

    Measured: At 60 months from treatment start

  4. Number of patients without events

    Event-free survival

    Measured: At 60 months from treatment start

  5. Number of Minimal Residual Disease-negative Complete Responses

    1. 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

    Measured: At 28 weeks from treatment start

  6. Number of adverse events

    1. 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).

    Measured: At 6.5 years after treatment start

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Mar 2015 (estimated)
  2. Study startOct 2015
  3. Primary completion3 Apr 2024
  4. Study completion3 Apr 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02388048
Sponsor's protocol ID
LLC1215
Other IDs
2015-000684-13, 2015
Status last verified
Jan 2025
First submitted
9 Mar 2015
Last updated
29 Jan 2025
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ibrutinib + ofatumumab in people with Leukemia, Lymphoblastic, Chronic, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 35 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 35 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02388048.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2025.

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