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Adult B Acute Lymphoblastic LeukemiaPhase 2NCT02129062

Ibrutinib in Treating Patients With Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia

A Phase 2 study testing Ibrutinib and Laboratory Biomarker Analysis in people with Adult B Acute Lymphoblastic Leukemia and Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1, run by National Cancer Institute (NCI) at 8 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase II trial studies how well ibrutinib works in treating patients with B-cell acute lymphoblastic leukemia that has come back after treatment or has not responded to other treatment. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ibrutinib and Laboratory Biomarker Analysis
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
8 sitesUnited States
Study dates
Apr 2014to Nov 2015
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

  • Relapsed or refractory B-ALL due to receive salvage 1, 2, 3, 4, 5, or 6; half of the patients, i.e. 5 out of the first 10 patients, and 5 out of 10 patients thereafter, need to be in earlier line of salvage therapy, defined as 1st, 2nd, or 3rd line of salvage therapy; Philadelphia chromosome-positive (Ph+) B-ALL patients must have failed treatment with at least 1 second generation tyrosine kinase inhibitor; patients in salvage 1 with late relapse should be deemed poor candidates for reinduction with initial therapy; patients with ALL of T cell origin (T-ALL) can not be treated
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Total bilirubin =< 1.5 × upper limit of normal (ULN) (unless Gilbert's syndrome or disease infiltration of the liver is present)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.0 × institutional ULN
  • Creatinine clearance (Cockcroft-Gault) greater than or equal to 30 mL/min or estimated (est) glomerular filtration rate (GFR) greater than or equal to 30 mL/min/1.73 m^2
  • For any surgery or invasive procedure requiring sutures or staples for closure, ibrutinib should be held at least 7 days prior to the intervention and should be held at least 7 days after the procedure, and restarted at the discretion of the investigator when the surgical site is reasonably healed without serosanguineous drainage or the need for drainage tubes
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  • Bone marrow involvement with >= 5% lymphoblasts, peripheral blast count less than 5,000 per uL
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; female patients need a negative serum or urine pregnancy test within 14 days of study start (applies only if patient is of childbearing potential); non-childbearing is defined as >= 1 year postmenopausal or surgically sterilized; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of ibrutinib administration
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Patients who receive other chemotherapy; patients must have been off previous therapy for >= 2 weeks and must have recovered from clinically significant toxicity (to grade 1 or less) of all previous therapy prior to enrollment (consent signing) with the following exceptions: steroids, hydroxyurea, oral mercaptopurine, methotrexate, vincristine (including prophylactic intrathecal medication), thioguanine, and tyrosine kinase inhibitors are permitted within 2 weeks of randomization as maintenance or to reduce the peripheral blood blast counts; during ibrutinib therapy, only steroids and hydroxyurea are permitted to reduce peripheral blood blast counts; patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier
  • Patients who are receiving any other investigational agents
  • Active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of CNS-directed local treatment for active disease within the prior 28 days, symptomatic CNS leukemia (i.e., cranial nerve palsies or other significant neurologic dysfunction) within 28 days; prophylactic intrathecal medication is not a reason for exclusion; patients with known brain metastases should be excluded from this clinical trial
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib
  • Concomitant use of drugs that strongly inhibit cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5)
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or an infection requiring systemic antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
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  • Pregnant and breastfeeding women are excluded from this study; breastfeeding should be discontinued if the mother is treated with ibrutinib
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are eligible, unless the patient's cluster of differentiation (CD)4 count is below the institutional lower limit of normal, or the patient is taking prohibited CYP3A4/5 strong inhibitors or inducers
  • Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP) resulting in (or as evidenced by) declining platelet or hemoglobin (Hgb) levels within the 4 weeks prior to first dose of study drug
  • Presence of transfusion-dependent thrombocytopenia
  • Prior exposure to ibrutinib
  • History of prior malignancy, with the exception of the following:
  • Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to screening and felt to be at low risk for recurrence by treating physician
  • Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease
  • Adequately treated cervical carcinoma in situ without current evidence of disease
  • Burkitt's or mixed lineage leukemia, T cell ALL
  • Isolated extramedullary relapse (i.e., testicular or CNS)
  • Patients with a cardiac ejection fraction (as measured by either multi gated acquisition scan [MUGA] or echocardiogram) < 45% are excluded; currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or history of myocardial infarction within 6 months prior to first dose with study drug
  • Unable to swallow capsules, or disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption, such as malabsorption syndrome, resection of the small bowel, or poorly controlled inflammatory bowel disease affecting the small intestine
  • Serologic status reflecting active hepatitis B or C infection; patients that are hepatitis B core antibody positive but antigen negative will need a negative polymerase chain reaction (PCR) prior to enrollment; (hepatitis B antigen or PCR positive patients will be excluded;) (this may not be a necessary exclusion for an ibrutinib monotherapy protocol)
  • History of stroke or intracranial hemorrhage within 6 months prior to enrollment
  • Current life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety, or put the study at risk; any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that may place the subject at undue risk to undergo therapy with ibrutinib
  • Any serious medical condition, laboratory abnormality, or psychiatric illness that places the subject at unacceptable risk if he/she were to participate in the study
  • Received anticoagulation therapy with warfarin or equivalent vitamin K antagonists within the last 28 days
  • Evidence of clinically significant bleeding diathesis or coagulopathy
  • Major surgical procedure, open biopsy, or significant traumatic injury, within 28 days prior to day 1, anticipation of need for major surgical procedure during the course of the study; (minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to day 1; bone marrow aspiration +/- biopsy is allowed)
  • Prior allogeneic stem cell transplant in previous 3 months

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Penn State Milton S Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

  • UC Davis Comprehensive Cancer Center LAPS

    Sacramento, California, 95817

  • Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: A Phase 2 Study to Determine the Efficacy of the BTK Inhibitor Ibrutinib (PCI-32765) in Patients With Relapsed or Refractory Precursor-B Lymphoblastic Leukemia (B-ALL)

This phase II trial studies how well ibrutinib works in treating patients with B-cell acute lymphoblastic leukemia that has come back after treatment or has not responded to other treatment. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the efficacy of ibrutinib in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) as measured by objective response rate (ORR).

SECONDARY OBJECTIVES:

  1. To evaluate the global safety profile of ibrutinib in patients with relapsed or refractory B-ALL.

II. To assess response duration. III. To assess Bruton's tyrosine kinase (BTK) target inhibition, biomarkers, and gene expression profiles in B-ALL patient samples before and during treatment with ibrutinib.

OUTLINE:

Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.

Being tested
Ibrutinib, Laboratory Biomarker Analysis
Medical subject headings
Burkitt Lymphoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma

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, PCI-32765

    Given orally 560 mg daily (dispensed as 4 x 140-mg capsules)

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT02129062
Study groupRoleWhat they receive
Treatment (ibrutinib)ExperimentalIbrutinib 560 mg orally daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Ibrutinib; Other: Laboratory Biomarker Analysis

What is being measured

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

  1. Objective Response Rate (ORR)

    ORR is defined as the proportion of participants with complete or partial response. Response definitions of Complete Response (CR): disappearance of leukemia as indicated by <5% marrow blasts \& absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by absolute neutrophil count (ANC) >1000/μL \& platelets >100,000/μL. C1 extramedullary disease status required. CR with incomplete count recovery (CRi): CR except with ANC <1000/μL and/or platelets <100,000/μL. Partial response (PR): improved or no worsening of ALL as indicated by no peripheral blood blasts, neutrophils >1000/μL, platelets >100,000μL, and either or both of the following: >50% decrease in marrow blast percentage, compared to pretreatment value, \& marrow blast percentage ≥ 5% and ≤ 25%. C2 extramedullary disease status. Treatment failures are defined as participants who fail to achieve CR, CRi or PR.

    Measured: 3 months after treatment

  2. Overall Survival Time

    The time measurement from beginning treatment to recurrent or progressive disease is objectively documented. Overall survival time will be estimated using the Kaplan-Meier method. The two-sided log-rank test will be used to assess the differences of time to events between groups such as age groups, or Philadelphia chromosome-positive versus Philadelphia chromosome-negative B-ALL. Progressive disease is defined as a doubling of the peripheral blasts and an absolute increase of > 5 x 10^9/L.

    Measured: Up to thirty days after after completion of study treatment anticipated to be 12 weeks for total of 16 weeks

Timeline

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

  1. First posted2 May 2014 (estimated)
  2. Study startApr 2014
  3. Primary completionNov 2015
  4. Study completionNov 2015

Why it stopped: Slow accrual.

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
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02129062
Sponsor's protocol ID
NCI-2014-00886
Other IDs
NCI-2014-00886, 2013-0459, 9543, P30CA016672, N01CM39
Status last verified
Nov 2016
First submitted
30 Apr 2014
Last updated
16 Jan 2017
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ibrutinib and Laboratory Biomarker Analysis in people with Adult B Acute Lymphoblastic Leukemia and Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1, run by National Cancer Institute (NCI) at 8 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 9 inclusion and 27 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: stopped early, as of the sponsor's last update on 16 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 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 16 Jan 2017). 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?

Objective Response Rate (ORR) (time frame: 3 months after treatment). 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 NCT02129062.

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 16 Jan 2017.

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