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Recurrent Chronic Lymphocytic LeukemiaPhase 2NCT03045328

Venetoclax and Ibrutinib in Patients With Relapsed/Refractory CLL or SLL

A Phase 2 study testing Ibrutinib and Venetoclax in people with Recurrent Chronic Lymphocytic Leukemia and Recurrent Small Lymphocytic Lymphoma, run by Steven E. Coutre at 2 sites in United States.

Completed

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

Official record
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Trial summary

This is an open-label non-randomized two-center phase 2 study evaluating the safety and efficacy of concurrent therapy with ibrutinib and venetoclax in subjects with relapsed or refractory CLL/SLL. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ibrutinib and Venetoclax
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
2 sitesUnited States
Study dates
26 Sep 2017to 5 Aug 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Subject must voluntarily sign and date an informed consent approved by the Institutional Review Board prior to initiation of any study specific procedures
  • Subject must have a diagnosis of CLL that meets International Workshop on Chronic Lymphocytic Leukemia (IWCLL)/National Cancer Institute (NCI)-Working Group (WG) criteria
  • Subject must have relapsed/refractory disease with an indication for treatment according to the 2008 IWCLL/NCI WG criteria
  • Measurable nodal disease by computed tomography (CT)
  • Absolute neutrophil count > 750 cells/mm^3 (0.75 x 10^9/L)
  • Platelet count > 30,000 cells/mm^3 (30 x 10^9/L)
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  • Hemoglobin > 8.0 g/dL
  • Serum aspartate transaminase (AST) or alanine transaminase (ALT) =< 2.5 x upper limit of normal (ULN)
  • Estimated creatinine clearance >= 30 mL/min (Cockcroft-Gault)
  • Bilirubin =< 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
  • Prothrombin time/international normalized ratio (PT/INR) < 1.5 x ULN and partial thromboplastin time (PTT) (activated [a]PTT) < 1.5 x ULN
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Female subjects who are of non-reproductive potential (ie, post-menopausal by history - no menses for >= 1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy); female subjects of childbearing potential must have a negative serum pregnancy test upon study entry
  • Male and female subjects must agree to use highly effective methods of birth control (eg, condoms, implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], sexual abstinence, or sterilized partner) during the period of therapy and for 90 days after the last dose of study drug

Who cannot join

  • Subject has previously received either venetoclax or ibrutinib
  • Subject has received a live virus vaccine within 28 days prior to the initiation of study treatment
  • Subject has undergone an allogeneic stem cell transplant in the past 1 year and must not have active chronic graft versus host disease (cGVHD) if over 1 year post allogeneic transplant
  • Subject has developed Richter's transformation confirmed by biopsy
  • Chemotherapy =< 21 days prior to first administration of study treatment and/or monoclonal antibody =< 6 weeks prior to first administration of study treatment
  • History of other malignancies, except:
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  • Malignancy treated with curative intent and with no known active disease present for >= 3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Adequately treated carcinoma in situ without evidence of disease
  • Concurrent systemic immunosuppressant therapy (eg, cyclosporine A, tacrolimus, etc, or chronic administration [> 14 days] of > 20 mg/day of prednisone) within 28 days of the first dose of study drug
  • Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug
  • Recent infection requiring systemic treatment that was completed =< 14 days before the first dose of study drug
  • Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version [v]4), grade =< 1, or to the levels dictated in the inclusion/exclusion criteria with the exception of alopecia
  • Known bleeding disorders (eg, von Willebrand's disease) or hemophilia
  • History of stroke or intracranial hemorrhage within 6 months prior to enrollment
  • Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus (HCV) or hepatitis B virus (HBV); subjects who are positive for hepatitis B core antibody or hepatitis B surface antigen must have a negative polymerase chain reaction (PCR) result before enrollment; those who are PCR positive will be excluded
  • Any uncontrolled active systemic infection
  • Major surgery within 4 weeks of first dose of study drug
  • Any life threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk
  • Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization
  • Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction
  • Concomitant use of warfarin or other vitamin K antagonists
  • Requires treatment with a strong cytochrome P450 (CYP) 3A4/5 inhibitor
  • Lactating or pregnant
  • Unwilling or unable to participate in all required study evaluations and procedures
  • Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations)

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • City of Hope

    Duarte, California, 91010

  • Stanford University, School of Medicine

    Stanford, California, 94305

Other trials in United States

About this study

Official title: An Open Label Phase 2 Trial of Venetoclax With Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

This is an open-label non-randomized two-center phase 2 study evaluating the safety and efficacy of concurrent therapy with ibrutinib and venetoclax in subjects with relapsed or refractory CLL/SLL.

Read the detailed description

The primary objective of this study is to evaluate the efficacy of concurrent therapy with ibrutinib and venetoclax in patients with relapsed and refractory chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL).

The secondary objectives of this study are to define the safety, tolerability, and dose-limiting toxicity (DLT) within 28 days of completion of dose-escalation.

Being tested
Ibrutinib, Venetoclax
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.

  • IbrutinibDrug

    Also called BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

    Administered at 420 mg/day, as oral capsules (3 x 140 mg), starting Day 1, Week 1.

  • VenetoclaxDrug

    Also called ABT-0199, ABT-199, ABT199, GDC-0199

    Administered as tablets, starting Day 1, Week 9, with dose increasing every 7 days through 5 dose levels (20 mg; 50 mg; 100 mg; 200 mg; 400 mg).

Study groups in NCT03045328
Study groupRoleWhat they receive
Treatment (ibrutinib, venetoclax)ExperimentalPatients receive ibrutinib PO QD beginning on week 1 day 1. Treatment with ibrutinib continues in the absence of disease progression or unacceptable toxicity. Patients also receive venetoclax PO QD beginning on week 9 day 1. Treatment with venetoclax continues up to week 61 day 7 in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Ibrutinib; Drug: Venetoclax

What is being measured

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

  1. Complete Response (CR)

    Complete Response (CR) will be assessed as the number of participants who, based on investigator assessment based on the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria, achieve a complete remission. IWCLL complete remission is defined as follows.

    • Lymphadenopathy: none > 1.5 cm
    • Blood lymphocytes: < 4,000/µL
    • Hepatomegaly: none
    • Splenomegaly: none
    • Bone marrow: normocellular with < 30 lymphocytes, no B lymphoid nodules.

    The outcome is reported as the number of participants who achieve CR, a number without dispersion.

    Measured: 62 weeks

Secondary outcomes (6)

  1. Duration of Response (DoR)

    Duration of response (DoR) refers to a participant maintaining clinical response after achieving either complete response (CR) or partial response (PR). The outcome is reported as the number of subjects who have maintained clinical response through 117 weeks. Response defined as the following.

    CR.

    • Lymphadenopathy: none > 1.5 cm
    • Blood lymphocytes: < 4,000/µL
    • Hepatomegaly: none
    • Splenomegaly: none
    • Bone marrow: normocellular with < 30 lymphocytes, no B lymphoid nodules. PR.
    • Lymphadenopathy: decrease ≥ 50%
    • Blood lymphocytes: decrease ≥ 50%
    • Hepatomegaly: decrease ≥ 50%
    • Splenomegaly: decrease ≥ 50%
    • Bone marrow: not considered.

    Measured: 117 weeks

  2. Minimal Residual Disease (MRD)

    Minimal residual disease (MRD) refers to the small numbers of leukemic cells that can remain in the participant after treatment, and may not be associated with any symptoms (remission). Although the participant may feel "healthy," the MRD is a major cause of eventual leukemic relapse. "MRD-negative" is the ideal treatment outcome. MRD negativity was defined as less than one leukemic cell per 10,000 leukocytes as assessed by bone marrow-based flow cytometry. The outcome is reported as the number of participants who were positive for MRD, or negative.

    Measured: 117 weeks

  3. Overall Response (OR)

    Overall response (OR) is the overall number of subjects that begin treatment and achieve a complete response (CR); partial response (PR); or Stable Disease (SD) 62 weeks after the beginning of treatment, according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria. IWCLL CR is defined as follows. The outcome is reported as the number of participants who achieve CR, PR, or SD, and number without dispersion.

    CR:

    • Lymphadenopathy: none > 1.5 cm
    • Blood lymphocytes: < 4,000/µL
    • Hepatomegaly: none
    • Splenomegaly: none
    • Bone marrow: normocellular with < 30 lymphocytes, no B lymphoid nodules.

    PR:

    • Lymphadenopathy: decrease ≥ 50%
    • Blood lymphocytes: decrease ≥ 50%
    • Hepatomegaly: decrease ≥ 50%
    • Splenomegaly: decrease ≥ 50%
    • Bone marrow: not considered.

    SD:

    • Lymphadenopathy: change of ± 49%
    • Blood lymphocytes: change of ± 49%
    • Hepatomegaly: change of ± 49%
    • Splenomegaly: change of ± 49%
    • Bone marrow: not considered.

    Measured: 62 weeks

  4. Overall Survival (OS)

    Overall survival (OS) represents the amount of time the participants remain alive after treatment. The outcome is reported as the number of participants remaining alive at 117 weeks (about 2 years and 3 months) after the start of treatment, a number without dispersion.

    Measured: Through 117 weeks

  5. Progression-free Survival (PFS)

    Progression-free survival (PFS) is a term that means to remain alive with progressive disease (PD). PD is defined as

    • Lymphadenopathy: Increase ≥ 50%
    • Blood lymphocytes: Increase ≥ 50%
    • Hepatomegaly: Increase ≥ 50%
    • Splenomegaly: Increase ≥ 50%
    • Bone marrow: not considered.

    The outcome is reported as the number of participants who remained alive without PD 117 weeks after the beginning of treatment.

    Measured: 117 weeks

  6. Time-to-progression (TTP)

    Time-to-progression (TTP) is a measure of the length of time from the beginning of treatment until progressive disease (PD). PD is defined as

    • Lymphadenopathy: Increase ≥ 50%
    • Blood lymphocytes: Increase ≥ 50%
    • Hepatomegaly: Increase ≥ 50%
    • Splenomegaly: Increase ≥ 50%
    • Bone marrow: not considered.

    The outcome will be reported as the median TTP as determined by Kaplan-Meier methodology, with 95% confidence interval (95% CI).

    Measured: Through 117 weeks

Timeline

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

  1. First posted7 Feb 2017 (estimated)
  2. Study start26 Sep 2017
  3. Primary completion19 May 2020
  4. Study completion5 Aug 2021

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
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03045328
Sponsor's protocol ID
IRB-36705
Other IDs
NCI-2017-00124, HEM0048
Status last verified
Sep 2021
First submitted
3 Feb 2017
Last updated
29 Sep 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ibrutinib and Venetoclax in people with Recurrent Chronic Lymphocytic Leukemia and Recurrent Small Lymphocytic Lymphoma, run by Steven E. Coutre at 2 sites in United States.

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 14 inclusion and 26 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 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. 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?

Yes. Results are posted in the registry (first posted 29 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Complete Response (CR) (time frame: 62 weeks). 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 NCT03045328.

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 Sep 2021.

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