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Chronic Lymphocytic LeukemiaPhase 1ZGR in TN CLLNCT06547944

Zanubrutinib, Obinutuzumab and Lenalidomide in Newly Diagnosed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

A Phase 1 study testing Zanubrutinib, Lenalidomide and Obinutuzumab in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Institute of Hematology & Blood Diseases Hospital, China at 1 site in China.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The ZGR regimen limited-course regimen was designed to combine three targeted agents, zanubrutinib, obinutuzumab (a third-generation CD20 monoclonal antibody), and lenalidomide, to deepen the depth of remission in patients with new-diagnosis CLL/SLL, with a view to achieving the goal of discontinuation of the drug and… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Zanubrutinib, Lenalidomide and Obinutuzumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteChina
Study dates
1 Jan 2024to 1 Dec 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 1） Patients were not categorized by gender ，Age ≥18;
  • 2） Confirmed diagnosis of CLL or SLL;
  • 3）Patients must be untreated, or not undergoing standardized treatment for the first time, under the following conditions:
  • a) Not treated with fludarabine-containing or bendamustine-containing or rituximab-containing regimens;
  • b) Have not been treated with the application of chlorambucil, or have applied chlorambucil for less than 4 weeks (alone or in combination with adrenal glucocorticoids);
  • (c) If the above treatment has been applied, it must be stopped for 2 weeks before enrollment in the group to start the treatment.
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  • 4） Indications for treatment of CLL/SLL include, inter alia (at least one of the following conditions is met)
  • Evidence of progressive bone marrow failure: as evidenced by progressive decrease in hemoglobin and/or platelets;
  • Giant spleen (e.g., >6 cm below the left costal margin) or symptomatic splenomegaly;
  • Giant lymph node enlargement (e.g., longest diameter >10 cm) or symptomatic lymph node enlargement;
  • Progressive lymphocytosis, e.g., >50% lymphocytosis within 2 months, or lymphocyte doubling time (LDT) <6 months. When initial lymphocytes are <30 x 10^9/L, LDT alone cannot be used as a therapeutic indication;
  • CLL/SLL resulting in symptomatic organ dysfunction (e.g., skin, kidney, lung, spine, etc.)
  • Autoimmune hemolytic anemia (AIHA) and/or immune thrombocytopenia (ITP) that does not respond well to corticosteroids or other standard therapy;
  • Presence of at least one of the following disease-related symptoms: i) weight loss ≥10% without apparent cause within the previous 6 months; ii) severe fatigue (e.g., ECOG physical status ≥2; inability to perform routine activities); iii) temperature >38°C for ≥2 weeks without evidence of infection; iv) nocturnal night sweats for >1 month without evidence of infection;
  • 5） ECOG≤2
  • 6) Major organ function within 7 days prior to treatment, meet the following criteria: routine blood test criteria: platelets ≥30×10^9/L; biochemical tests need to meet the following criteria: total bilirubin (TBIL) ≤1.5 times the upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase AST ≤2.5 ULN; creatinine clearance ≥ 30 ml/min; and cardiac Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ low limit of normal (50%);
  • 7) Male and female patients of childbearing age agree to use reliable contraception throughout the study period and for 4 weeks after the end of study treatment;
  • 8) Patients need to have an expected survival of ≥ 6 months;
  • 9) Patients need to voluntarily participate in this study by signing an informed consent form.

Who cannot join

  • Patients who met any of the following criteria were excluded from the study:
  • (1) Malignancies other than CLL/SLL (including active CNS lymphoma) have been diagnosed or treated within the past year;
  • (2) There has been clinical evidence of Richter transformation;
  • (3) Non-lymphoma-related hepatic and renal impairment: alanine aminotransferase (ALT) > 3 times the upper limit of normal, alanine transaminase (AST) > 3 times the upper limit of normal, total bilirubin (TBIL) > 2 times the upper limit of normal, and serum creatinine clearance < 30 ml/min;
  • (4) Other serious medical disorders that would interfere with the study (e.g., uncontrolled diabetes mellitus, gastric ulcers, grade 3 or 4 atrial fibrillation or persistent atrial fibrillation of any grade, other serious cardiorespiratory diseases, etc.). The judgmental decision is vested in the investigator;
  • (5) Patient who had infected with Human Immunodeficiency Virus (HIV) or active Hepatitis B Virus (HBV) infection, or any uncontrolled active systemic infection requiring intravenous antibiotics;
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  • (6) Clinically manifested CNS dysfunction or invasion of the center;
  • (7) Patients who have undergone a major surgical procedure (excluding lymph node biopsy) within the last 14 days or who require a major surgical procedure in anticipation of treatment;
  • (8) Inability to swallow capsules or suffering from malabsorption syndromes, disorders significantly affecting gastrointestinal function, having undergone gastric or small bowel resection, symptomatic inflammatory bowel disease or ulcerative colitis, and partial or complete intestinal obstruction.
  • (9) Requires treatment with potent cytochrome P450 (CYP) 3A inhibitors;
  • (10) Pregnant or lactating women of childbearing age who are not using contraception;
  • (11) Patients with clinically significant cardiovascular abnormalities (New York Heart Association (NYHA) classification: III/IV), myocardial infarction within 6 months prior to enrollment, malignant arrhythmias (including QTC ≥ 480 ms), poorly controlled blood pressure (systolic ≥ 150 mmHg, diastolic ≥ 100 mmHg) despite the use of antihypertensive medications, and uncontrolled angina;
  • (12) Persistent uncontrolled bleeding;
  • (13) History of life-threatening hemorrhage, especially from irreversible causes;
  • (14) Need for high doses of several anticoagulants that cannot be briefly discontinued;
  • (15) Thrombotic events within three months of treatment initiation;
  • (16) Patients with severe hypersensitivity to the active ingredient of the study drug or to any of its excipients;

Trial locations and contacts

1 site in 1 country.

China1 site

  • Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College

    Tianjin, Tianjin Municipality

Other trials in China

About this study

Official title: A Phase 1b Clinical Study of Lenalidomide in Combination With Zanubrutinib and Obinutuzumab (ZGR) in the Treatment of Newly Diagnosed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) With Therapeutic Indications

The ZGR regimen limited-course regimen was designed to combine three targeted agents, zanubrutinib, obinutuzumab (a third-generation CD20 monoclonal antibody), and lenalidomide, to deepen the depth of remission in patients with new-diagnosis CLL/SLL, with a view to achieving the goal of discontinuation of the drug and long-term remission after discontinuation of the drug, and prolonging the PFS, and at the same time, the regimen no longer includes cytotoxic chemotherapeutic agents, such as fludarabine and cyclophosphamide, which improves the CLL/ SLL patients' treatment tolerance, and can eliminate the treatment limitation for elderly or poorly tolerated CLL/SLL patients.

Read the detailed description

BTK inhibitor monotherapy for CLL/SLL can obtain 80-90% ORR and give patients long-term survival, but most patients only obtain PR efficacy, even after up to 7-8 years of continuous treatment, the proportion of patients with CR can only be improved from less than 10% to about 30%, and it is very difficult for any patient to achieve MRD negativity, so it is determined that the mode of treatment of BTK inhibitor monotherapy is long-term continuous administration for tumor control. In order to change this pattern of long-term continuous treatment, and to shorten the long-term continuous treatment to a limited cycle of treatment, it is necessary to deepen the depth of remission by combining the treatment with other mechanisms of drugs, or even to achieve MRD-negativity in order to realize the discontinuation of the drug.

Lenalidomide is an oral immunomodulatory drug with direct antitumor effects and indirect antitumor effects by acting on a variety of immune cells in the tumor microenvironment. Lenalidomide alone, in combination with CD20 monoclonal antibody (rituximab), or (and) BTK inhibitors for the treatment of R/R CLL/SLL has shown therapeutic responses, with the best response to triple therapy of lenalidomide in combination with rituximab and BTK inhibitors. combination therapy showed the best response.

The ZGR limited-course regimen that combines zanubrutinib, obinutuzumab, and lenalidomide in the treatment of patients with primary diagnosis of CLL/SLL, which can deepen the depth of remission, with a view to achieving the goal of discontinuation of the drug and long-term remission after discontinuation of the drug, and prolonging the PFS, and at the same time, the regimen are removed cytotoxic chemotherapeutic agents, such as fludarabine, to increase the tolerance of the treatment in patients with CLL/SLL, and can eliminate the need for treatment of elderly or poorly tolerated patients with CLL/SLL. treatment limitations in poorly tolerated CLL/SLL patients.

Being tested
Zanubrutinib, Lenalidomide, Obinutuzumab
Keywords
Zanubrutinib, Lenalidomide, Obinutuzumab, newly diagnosed CLL/SLL
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

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

  • ZanubrutinibDrug

    160mg bid/d, from C1 to CR and MRD-negative or C24

  • LenalidomideDrug

    From C3 dose escalation, all 3 dose groups climbed from 5 mg/d to 10 mg/d, 15 mg/d, and 20 mg/d respectively, Taking 21 days of medication and 7 days of rest, 1 cycle every 28 days to CR and MRD-negative or C24

  • ObinutuzumabDrug

    1000 mg C1, d1/d8/15; 1000 mg C2-6, d1

Study groups in NCT06547944
Study groupRoleWhat they receive
ZGR regimenExperimentalDose Escalation lenalidomide combined with Zanubrutinib and Obinutuzumab (Dose escalation will occur using a 3+3 design) Recommended phase II dose (RP2D) lenalidomide combined with Zanubrutinib and Obinutuzumab
Receives: Drug: Zanubrutinib; Drug: Lenalidomide; Drug: Obinutuzumab

What is being measured

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

  1. Maximum Tolerated Dose (MTD) of lenalidomide in combination regimens were determined in newly diagnosed CLL/SLL patients,

    Measured: From the date of first dose of study drugs until RP2D was determined(Approximately 4 months)]

  2. The incidence, nature and severity of adverse events (AE) were determined according to NCI-CTCAE v5.0 evaluation criteria

    Measured: From first dose to 30 days after the last dose of Zanubrutinib or lenalidomide or Obinutuzumab

Secondary outcomes (4)

  1. overall response rate(ORR)

    Defined as the proportion of patients assessed as CR, CRi, or PR according to the IWCLL 2018 criteria at or before initiation of subsequent antitumor therapy.

    Measured: From first dose to 30 days after the last dose of Zanubrutinib or lenalidomide or Obinutuzumab

  2. overall survival Overall survival(OS)

    Defined as the time interval from enrollment to death for patients in an intentional-treatment population (ITT). If the patient continues to survive or if his or her life is unknown, the date of death will be the nearest point in time when the patient is known to be alive.

    Measured: Up to 5 years

  3. Progress-free survival(PFS)

    Defined as the time interval from enrollment to disease progression or death of a patient in an intention-to-treat population (ITT), whichever comes first. For those who did not progress at the time of exit or whose time to disease progression was not recorded, the last examination date was used as the end date.

    Measured: Up to 5 years

  4. Duration of tumor remission(DOR)

    Defined as the time interval between first recorded disease remission and first recorded evidence of PD in patients in an intention-to-treat population (ITT). No progression or time to disease progression was recorded at the time of exit from the trial, with the date of last examination as the end date.

    Measured: Up to 5 years

Timeline

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

  1. First posted9 Aug 2024
  2. Study start1 Jan 2024
  3. Primary completion1 Dec 2025 (estimated)
  4. Study completion1 Dec 2026 (estimated)

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06547944
Sponsor's protocol ID
IIT2023063
Acronym
ZGR in TN CLL
Status last verified
Jun 2024
First submitted
28 Jul 2024
Last updated
9 Aug 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Tam CS, Brown JR, Kahl BS, Ghia P, Giannopoulos K, Jurczak W, Simkovic M, Shadman M, Osterborg A, Laurenti L, Walker P, Opat S, Chan H, Ciepluch H, Greil R, Tani M, Trneny M, Brander DM, Flinn IW, Grosicki S, Verner E, Tedeschi A, Li J, Tian T, Zhou L, Marimpietri C, Paik JC, Cohen A, Huang J, Robak T, Hillmen P. Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial. Lancet Oncol. 2022 Aug;23(8):1031-1043. doi: 10.1016/S1470-2045(22)00293-5. Epub 2022 Jul 7.

    PubMed 35810754

  • Ferrajoli A, Lee BN, Schlette EJ, O'Brien SM, Gao H, Wen S, Wierda WG, Estrov Z, Faderl S, Cohen EN, Li C, Reuben JM, Keating MJ. Lenalidomide induces complete and partial remissions in patients with relapsed and refractory chronic lymphocytic leukemia. Blood. 2008 Jun 1;111(11):5291-7. doi: 10.1182/blood-2007-12-130120. Epub 2008 Mar 11.

    PubMed 18334676

  • Badoux XC, Keating MJ, Wen S, Lee BN, Sivina M, Reuben J, Wierda WG, O'Brien SM, Faderl S, Kornblau SM, Burger JA, Ferrajoli A. Lenalidomide as initial therapy of elderly patients with chronic lymphocytic leukemia. Blood. 2011 Sep 29;118(13):3489-98. doi: 10.1182/blood-2011-03-339077. Epub 2011 Jul 1.

    PubMed 21725050

  • Badoux XC, Keating MJ, Wen S, Wierda WG, O'Brien SM, Faderl S, Sargent R, Burger JA, Ferrajoli A. Phase II study of lenalidomide and rituximab as salvage therapy for patients with relapsed or refractory chronic lymphocytic leukemia. J Clin Oncol. 2013 Feb 10;31(5):584-91. doi: 10.1200/JCO.2012.42.8623. Epub 2012 Dec 26.

    PubMed 23270003

  • Ujjani C, Wang H, Skarbnik A, Trivedi N, Ramzi P, Khan N, Cheson BD. A phase 1 study of lenalidomide and ibrutinib in combination with rituximab in relapsed and refractory CLL. Blood Adv. 2018 Apr 10;2(7):762-768. doi: 10.1182/bloodadvances.2017015263.

    PubMed 29610115

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Zanubrutinib, Lenalidomide and Obinutuzumab in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Institute of Hematology & Blood Diseases Hospital, China at 1 site in China.

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 19 inclusion and 17 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: under way, not looking for participants, as of the sponsor's last update on 9 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Maximum Tolerated Dose (MTD) of lenalidomide in combination regimens were determined in newly diagnosed CLL/SLL patients, (time frame: From the date of first dose of study drugs until RP2D was determined(Approximately 4 months)]). The study lists 2 primary outcomes in all. 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 NCT06547944, which also lists 5 linked publications.

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 9 Aug 2024.

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