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Acute Biphenotypic LeukemiaPhase 2NCT03267186

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

A Phase 2 study testing Ibrutinib and Laboratory Biomarker Analysis in people with Acute Biphenotypic Leukemia and Acute Lymphoblastic Leukemia, run by Andrew Rezvani at 1 site 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 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. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Ibrutinib and Laboratory Biomarker Analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
1 siteUnited States
Study dates
12 Sep 2017to 30 Apr 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 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Stanford University, School of Medicine

    Palo Alto, California, 94304

Other trials in United States

About this study

Official title: 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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
Ibrutinib, Laboratory Biomarker Analysis
Medical subject headings
Leukemia, Biphenotypic, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Leukemia, Myelogenous, Chronic, BCR-ABL Positive

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

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT03267186
Study groupRoleWhat they receive
Prevention (ibrutinib)ExperimentalBeginning 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.
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. Number of Participants With Relapsed Leukemia

    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.

    Measured: Up to 18 months

Secondary outcomes (3)

  1. Number of Participants With Acute Graft-versus-host Disease (GVHD) (Any Grade)

    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

    Measured: At 180 days

  2. Number of Participants With Chronic GVHD

    Assessment of chronic GvHD was performed using the 2015 NIH consensus criteria.

    Measured: At 18 months

  3. Number of Participants Negative for Detectable Minimal Residual Disease

    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.

    Measured: day +90, day +180, 1 year, 1.5 years

Timeline

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

  1. First posted30 Aug 2017
  2. Study start12 Sep 2017
  3. Primary completion30 Apr 2021
  4. Study completion30 Apr 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
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03267186
Sponsor's protocol ID
IRB-38934
Other IDs
NCI-2017-00125, IRB-38934, BMT302
Status last verified
Jul 2023
First submitted
28 Aug 2017
Last updated
1 Aug 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, Palmer J, Weisdorf D, Treister NS, Cheng GS, Kerr H, Stratton P, Duarte RF, McDonald GB, Inamoto Y, Vigorito A, Arai S, Datiles MB, Jacobsohn D, Heller T, Kitko CL, Mitchell SA, Martin PJ, Shulman H, Wu RS, Cutler CS, Vogelsang GB, Lee SJ, Pavletic SZ, Flowers ME. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015 Mar;21(3):389-401.e1. doi: 10.1016/j.bbmt.2014.12.001. Epub 2014 Dec 18.

    PubMed 25529383

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ibrutinib and Laboratory Biomarker Analysis in people with Acute Biphenotypic Leukemia and Acute Lymphoblastic Leukemia, run by Andrew Rezvani at 1 site 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 25 inclusion and 30 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 1 Aug 2023. 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 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 1 Aug 2023). 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?

Number of Participants With Relapsed Leukemia (time frame: Up to 18 months). 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 NCT03267186, which also lists 1 linked publication.

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 1 Aug 2023.

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