Ibrutinib in Preventing Acute Leukemia in Patients After Reduced-Intensity Conditioning and Stem Cell Transplant

July 11, 2023 updated by: Andrew Rezvani

A Phase 2 Study of Ibrutinib Maintenance After Reduced-Intensity Conditioning and Allogeneic Hematopoietic Cell Transplantation for Acute Leukemia

This phase II trial studies how well ibrutinib works in preventing acute leukemia in patients after reduced-intensity conditioning and stem cell transplant. Ibrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

PRIMARY OBJECTIVES:

I. To reduce the incidence of relapse at 18 months after reduced-intensity conditioning (RIC) and allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML) in blast crisis from a historical baseline of 45% to 25%, using ibrutinib maintenance therapy.

SECONDARY OBJECTIVES:

I. To study the incidence and severity of post-transplant complications in subjects receiving ibrutinib maintenance after allogeneic HCT.

II. To study the incidence of infectious complications in subjects receiving maintenance ibrutinib after allogeneic HCT.

III. To study the impact of ibrutinib maintenance on minimal residual disease after RIC and allogeneic HCT.

IV. To study the impact of maintenance ibrutinib on immune reconstitution and alloreactivity after allogeneic HCT, specifically on Th1/ Th2 polarization, T follicular cell number, T and B cell repertoire, serum immunoglobulin levels, and alloantibody formation.

OUTLINE:

Beginning 60-90 days after allogeneic HCT, patients receive ibrutinib orally (PO) once daily (QD) for up to 18 months post-transplant in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 2 years.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
8

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Palo Alto, California, United States, 94304
        • Stanford University, School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • INCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT)
  • Diagnosis of acute myeloid leukemia (AML), acute biphenotypic leukemia, or acute lymphoblastic leukemia (ALL); CML transformed to blast crisis is eligible
  • Planned allogeneic HCT using fludarabine phosphate (FLU)/melphalan hydrochloride (MEL) or FLU/busulfan (BU) conditioning
  • Planned graft versus host disease (GVHD) prophylaxis consisting of tacrolimus (TAC)/methotrexate (MTX) or TAC/sirolimus (SRL)
  • Human leukocyte antigen (HLA) identical sibling donor, HLA matched unrelated donor, or donor mismatched at 1 HLA allele or antigen
  • Less than or equal to 5% blasts on bone marrow examination within 60 days of starting conditioning
  • Age >= 18 years and =< 70 years
  • Able to give informed consent

  • Subjects will be eligible if their planned conditioning regimen for allogeneic HCT consists of one of the two following standard reduced intensity conditioning regimens:

    • FLU/MEL: fludarabine phosphate (fludarabine) 120 to 180 mg/m^2; melphalan hydrochloride (melphalan) =< 150 mg/m^2
    • FLU/BU: fludarabine 120 to 180 mg/m^2; busulfan =< 8 mg/kg orally or =< 6.4 mg/kg intravenously

  • Subjects will be eligible if their planned post grafting immunosuppression consists of one of the two following regimens:

    • TAC/MTX: tacrolimus (oral or intravenous) and intravenous methotrexate administered according to institutional standard practice.
    • TAC/SRL: tacrolimus (oral or intravenous) and oral sirolimus, administered according to institutional standards of care
  • INCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION)
  • Age >= 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
  • Absolute neutrophil count (ANC) > 0.75 x 10^9/L
  • Platelet count > 50 x 10^9/L
  • Hemoglobin > 8.0 g/dL without transfusion or growth factor support for at least 7 days prior to screening (with the exception of pegylated granulocyte-colony stimulating factor [G-CSF] and darbopoietin, which require at least 14 days of abstinence prior to screening)
  • Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 x upper limit of normal
  • Estimated creatinine clearance >= 30 mL/min via Cockroft-Gault formula
  • Bilirubin =< 1.5 x upper limit of normal (unless elevated bilirubin is due to Gilbert's syndrome or of non-hepatic origin)
  • Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) (activated partial thromboplastin time [aPTT]) =< 1.5 x upper limit of normal
  • 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 screening
  • Male and female subjects who agree to use both a highly effective method of birth control (eg, implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], sexual abstinence, or sterilized partner) and a barrier method (eg, condoms, vaginal ring, sponge, etc) during the period of therapy and for 30 days after the last dose of study drug for females and 90 days after the last dose of the study drug for males
  • Between day +60 and day +90 after allogeneic HCT

Exclusion Criteria:

  • EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): Active involvement of the central nervous system with malignancy (previous central nervous system [CNS] involvement is allowed if clearance of CNS disease has been documented prior to enrollment)
  • EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): Pregnant or breastfeeding
  • EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): Karnofsky performance status < 60%
  • EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): Active leukemia (> 5% leukemic blasts in peripheral blood or bone marrow)
  • EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): Non-hematologic malignancy with a life expectancy of < 5 years
  • EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): Known history of human immunodeficiency virus (HIV) or active hepatitis C virus (HCV) or hepatitis B virus (HBV) infection; 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
  • EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): Known bleeding disorders (eg, von Willebrand's disease) or hemophilia

  • EXCLUSION CRITERIA FOR ENROLLMENT (PRE-TRANSPLANT): History of other malignancies, except:

    • 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
  • EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Active and uncontrolled acute GVHD grades III or IV
  • EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Use of secondary therapy for acute GVHD at any time (defined as any systemic therapy intended to treat acute GVHD besides corticosteroids)
  • EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Requirement for anticoagulation with warfarin or other vitamin K antagonists (concomitant use of other anticoagulants is permitted)
  • EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Relapsed leukemia (> 5% leukemic blasts in peripheral blood or bone marrow after allogeneic HCT)
  • EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Karnofsky performance status < 60%
  • EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Chemotherapy =< 21 days prior to first administration of study treatment and/or monoclonal antibody =< 6 weeks prior to first administration of study treatment
  • EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug
  • EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): 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
  • EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): History of stroke or intracranial hemorrhage within 6 months prior to screening
  • EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): 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
  • EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Major surgery within 4 weeks of first dose of study drug
  • EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Any uncontrolled active systemic infection
  • EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Unresolved toxicities from prior anti cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version 4), grade =< 1, or to the levels dictated in the inclusion/exclusion criteria with the exception of alopecia
  • EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): 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
  • EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Requires treatment with a strong cytochrome P450 (CYP) 3A4/5 inhibitor
  • EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Unwilling or unable to participate in all required study evaluations and procedures
  • EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): 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)
  • EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Currently active, clinically significant hepatic impairment (Child-Pugh class B or C)
  • EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Lactating or pregnant
  • EXCLUSION CRITERIA (PRIOR TO IBRUTINIB ADMINISTRATION): Uncontrolled cardiac arrhythmias

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Prevention (ibrutinib)
Beginning 60-90 days after allogeneic HCT, patients receive ibrutinib PO QD for up to 18 months post-transplant in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Ibrutinib
Given PO
Other Names:
  • PCI-32765
  • Imbruvica
  • BTK Inhibitor PCI-32765
  • CRA-032765

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Relapsed Leukemia
Time Frame: Up to 18 months
Relapsed leukemia is defined as > 5% leukemic blasts detected in bone marrow or peripheral blood. Participants were also be considered to have relapsed leukemia if they receive any active treatment for progressive leukemia after allogeneic HCT, even if they have < 5% leukemic blasts. Withdrawal of immunosuppression alone is not considered an active treatment for progressive disease.
Up to 18 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Acute Graft-versus-host Disease (GVHD) (Any Grade)
Time Frame: At 180 days

Acute GVHD grades II-IV and III-IV was evaluated according to the following criteria.

Stage of Acute GvHD was assessed as follows.

  • Stage 1: Skin: rash < 25% of skin. Liver: bilirubin 2 to 3 mg/dL. Gut: diarrhea >500 mL/day or upper-gut symptoms with positive histology
  • Stage 2: Skin: rash 25 to 50% of skin. Liver: bilirubin 3 to 6 mg/dL. Gut: diarrhea >1000 mL/day.
  • Stage 3: Skin: rash > 50% of skin. Liver: bilirubin 6 to 15 mg/dL. Gut: diarrhea > 1500 mL/day.
  • Stage 4: Skin: generalized erythroderma with bulla formation. Liver: bilirubin > 15 mg/dL. Gut: diarrhea > 2500 mL/day or severe abdominal pain with or without ileus

Grade of Acute GvHD was determined as follows.

  • Grade 1: Stage 1-2 Skin + No Liver stage + No Gut stage
  • Grade 2: Stage 3 Skin OR Stage 1 Liver or Stage 1 Gut
  • Grade 3: No Skin stage + Stage 2 to 3 Liver Stage 2 to 4 Gut
  • Grade 4: Stage 4 Skin + or Stage 2 to 3 Liver + No Gut stage
At 180 days
Number of Participants With Chronic GVHD
Time Frame: At 18 months
Assessment of chronic GvHD was performed using the 2015 NIH consensus criteria.
At 18 months
Number of Participants Negative for Detectable Minimal Residual Disease
Time Frame: day +90, day +180, 1 year, 1.5 years
Detectable minimal residual disease was assessed using high-throughput sequencing (ClonoSEQ) and high-sensitivity flow cytometry. Minimal residual disease was considered present if > 1 x 10^-6 leukemic clones are detected by ClonoSEQ, or if any aberrant blasts matching the original leukemic immunophenotype are detected by high-sensitivity flow cytometry.
day +90, day +180, 1 year, 1.5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Andrew Rezvani

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institutes of Health (NIH)
Pharmacyclics LLC.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Andrew Rezvani, Stanford University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 12, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 30, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 28, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 28, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 30, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 1, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 11, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB-38934 (Other Identifier: Stanford IRB)
  • NCI-2017-00125 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • BMT302 (Other Identifier: OnCore)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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