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Blastoid Variant Mantle Cell LymphomaPhase 2NCT02869633

Ibrutinib in Treating Patients With Refractory or Relapsed Lymphoma After Donor Stem Cell Transplant

A Phase 2 study testing Ibrutinib and Laboratory Biomarker Analysis in people with Blastoid Variant Mantle Cell Lymphoma and Recurrent Chronic Lymphocytic Leukemia, run by Vanderbilt-Ingram Cancer Center at 5 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 phase II trial studies how well ibrutinib works in treating patients after a donor stem cell transplant for lymphoma that is not responding to treatment or has come back. 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
23 participants
Where
5 sitesUnited States
Study dates
Nov 2016to Oct 2023
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

  • PRE-STEM CELL TRANSPLANT (SCT)
  • Patients undergoing their first T cell replete allo-HCT for chronic lymphocytic leukemia (CLL), Hodgkin Lymphoma (HL), or the following subtypes of Non-Hodgkin lymphoma: Mantle cell lymphoma (MCL) and follicular center cell lymphoma (FL)
  • Meeting institutional criteria for allo-HCT. Ejection fraction by echocardiogram or MUGA >40%, pulmonary function test with adjusted DLCO ≥ 60%
  • Matched (8/8) or mismatched (7/8) related, unrelated HCT
  • Stem cell source: bone marrow, peripheral blood stem cell
  • Disease criteria:
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  • Cohort A
  • Chronic lymphocytic leukemia
  • Disease burden: lymph node size < 5 cm and/or extra-nodal involvement < 5 cm AND
  • 17 p deletion (detected by any assay) (> or equal to 20% of cells involved if assay is conventional cytogenetics or fluorescence in situ hybridization [FISH]) or NOTCH mutation at any time point during disease course; patient should have received at least 1 line of therapy; prior ibrutinib therapy is permitted OR
  • Relapsed/refractory chronic lymphocytic leukemia > or equal to 2 lines of therapy; prior ibrutinib therapy is permitted
  • Mantle cell lymphoma
  • Disease burden: lymph node size < 5 cm and/or extra-nodal involvement < 5 cm AND
  • Relapsed/refractory mantle cell lymphoma > or equal to 1 line of therapy. Prior ibrutinib therapy is permitted. Prior autologous hematopoietic cell transplant is permitted. OR
  • Mantle cell lymphoma blastoid variant in first complete response (CR1) or high risk mantle cell lymphoma being considered for allo hematopoietic cell transplant in CR1
  • Cohort B
  • Follicular lymphoma
  • Disease burden: lymph node size < 5 cm and/or extra-nodal involvement < 5 cm AND Relapsed/refractory follicular lymphoma > or equal to 2 lines of therapy. Prior ibrutinib therapy is permitted
  • Hodgkin disease
  • Disease burden: lymph node size < 5 cm and/or extra-nodal involvement < 5 cm AND
  • Relapsed/refractory Hodgkin disease > or equal to 2 lines of therapy.
  • Preparative regimen: both reduced intensity and ablative regimens are permitted. Each center will pre-specify the regimen they intend to use during the conduct of the study
  • Donor criteria: HLA ≥ 7/8 related or unrelated donors.
  • Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men must agree to not donate sperm during and after the study. For females, these restrictions apply for 1 month after the last dose of study drug. For males, these restrictions apply for 3 months after the last dose of study drug.
  • Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) or urine pregnancy test at screening. Women who are pregnant or breastfeeding are ineligible for this study
  • Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study
  • Prior to Administration of Ibrutinib (Day 60 to Day 90 post hematopoietic cell transplant)
  • Karnofsky performance status (KPS) > or equal to 60%
  • Engraftment of neutrophils (absolute neutrophil count [ANC] >= 1.0 X 10^9/L) for 3 days without granulocyte colony-stimulating factor (g-csf) support
  • Platelets > or equal to 100,000/mm^3 or > or equal to = 50,000/mm^3 if bone marrow involvement independent of transfusion support in either situation
  • Glomerular filtration rate (GFR) > or equal to 30 ml/min
  • Liver function tests (LFTs) (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) equal to or < 3 X upper limit of normal (ULN)
  • Total bilirubin equal to or < 1.5 mg/dL X ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin
  • Predominant donor chimerisms of > or equal to 51% as measured by CD3 and CD33 (or other myeloid marker)

Who cannot join

  • PRE-SCT
  • Progression of chronic lymphocytic leukemia or mantle cell lymphoma or follicular lymphoma or HD at time of transplant
  • Use of Coumadin (warfarin) or other vitamin-K antagonists for anticoagulation; non-Coumadin anticoagulation is permitted
  • Known central nervous system involvement
  • Active uncontrolled bacterial or invasive fungal infections
  • History of malignancy other than the underlying disease unless treated with a curative intent and/or no evidence of disease for at least 3 years (y) OR expected to be cured with SCT
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  • Planned use of post-hematopoietic cell transplant cyclophosphamide for graft versus host disease prophylaxis
  • Anticipated planned donor lymphocyte infusion in the first 3 months post-SCT
  • T deplete hematopoietic cell transplant
  • Umbilical cord hematopoietic cell transplant
  • History of stroke or intracranial hemorrhage within 6 months of enrollment
  • Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
  • Known HIV
  • Active Hepatitis B or C virus
  • Child-Pugh Class C
  • PRIOR TO ADMINISTRATION OF IBRUTINIB (DAY 60-DAY 90 POST SCT)
  • In the critical care unit, or use of mechanical ventilation or use of renal replacement therapy at any time post hematopoietic cell transplant and prior to administration of ibrutinib
  • Active uncontrolled stage 3-4 acute gastrointestinal (GI) graft versus host disease prior to administration of ibrutinib
  • Active uncontrolled stage 4 acute liver graft versus host disease prior to administration of ibrutinib
  • Evidence of progressive disease as compared to pre-hematopoietic cell transplant (persistence of disease is permitted)
  • Anticipated planned donor lymphocyte infusion in the first 3 months post-SCT
  • Active uncontrolled bacterial or invasive fungal infections
  • Prednisone equivalent of > 2m/kg for treatment of graft versus host disease prior to administration of ibrutinib
  • Use of second line systemic therapy for treatment of acute graft versus host disease prior to administration of ibrutinib
  • Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk. Including the presence of chronic/active HBV and HBC infections and Child-Pugh Class C.ibrutinib.
  • Major surgery or a wound that has not fully healed within 4 weeks of starting.
  • Requires anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon)
  • Requires chronic treatment with strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitors
  • Vaccinated with live, attenuated vaccines within 4 weeks of starting ibrutinib

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Stanford Cancer Institute

    Palo Alto, California, 94304

Other trials in United States

About this study

Official title: Optimizing Post-allogeneic Hematopoietic Cell Transplant Outcomes for Lymphoma Using Ibrutinib

This phase II trial studies how well ibrutinib works in treating patients after a donor stem cell transplant for lymphoma that is not responding to treatment or has come back. 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 study the use of ibrutinib starting between day 60 and day 90 after allogeneic hematopoietic cell transplant (HCT) until 12 months post hematopoietic cell transplant to improve the progression-free survival (PFS) at 12 months post hematopoietic cell transplant by 25% compared to historical controls.

SECONDARY OBJECTIVES:

  1. To increase the incidence of successful outcome (defined as lack of requirement of second line therapy for acute graft-versus-host disease, lack of National Institutes of Health [NIH] severe chronic graft-versus-host disease, lack of progression or relapse of chronic lymphocytic leukemia/mantle cell lymphoma [MCL], lack of death from disease or non-relapse causes) to at least 60% at 1 year post hematopoietic cell transplant. (Cohort A) II. To study the safety and tolerability of ibrutinib post hematopoietic cell transplant in patients with non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma. (Cohort A and B combined) III. To study the incidence of grade 3-4 acute graft-versus-host disease in the first 6 months post hematopoietic cell transplant in patients with non-Hodgkin lymphoma and Hodgkin lymphoma. (Cohort A and B combined) IV. To study the incidence of second line therapy (systemic only) for acute graft-versus-host disease in the first 6 months post hematopoietic cell transplant in patients with non-Hodgkin lymphoma and Hodgkin lymphoma. (Cohort A and B combined) V. To study the incidence of recurrent acute graft-versus-host disease in the first 6 months post hematopoietic cell transplant in patients with non-Hodgkin lymphoma and Hodgkin lymphoma. (Cohort A and B combined) VI. To study the incidence and severity of chronic graft-versus-host disease in the first 12 months post hematopoietic cell transplant in patients with not-Hodgkin lymphoma and Hodgkin lymphoma. (Cohort A and B combined) VII. To study the incidence of lung involvement with graft-versus-host disease in the first 12 months post hematopoietic cell transplant in patients with non-Hodgkin lymphoma and Hodgkin lymphoma. (Cohort A and B combined) VIII. To study the incidence of sclerotic skin chronic graft-versus-host disease in the first 12 months post hematopoietic cell transplant in patients with non-Hodgkin lymphoma and Hodgkin lymphoma. (Cohort A and B combined) IX. To study the incidence of infectious deaths not related to graft-versus-host disease in patients with non-Hodgkin and Hodgkin lymphoma. (Cohort A and B combined)

TERTIARY OBJECTIVES:

  1. To study the association of minimal residual disease (MRD) as detected by immunoglobulin heavy chain (IgH) sequencing prior to starting ibrutinib and compare to post ibrutinib at month 6, 9 and 12 after HCT. (Cohort A)

II. To study the impact of onset of new acute or chronic graft-versus-host disease on minimal residual disease. (Cohort A)

III. To study the association of T-cell clonality by T cell receptor (TCR) Vb sequencing prior to starting ibrutinib and compare to post ibrutinib at month 6, 9 and 12 after hematopoietic cell transplant. (Cohort A)

IV. To study the impact of onset of new acute or chronic graft-versus-host disease on T cell receptor sequencing. (Cohort A)

  1. To study the association of B cell receptor signaling pathways and immune function with response by single cell mass cytometry prior to starting ibrutinib and compare to post ibrutinib at month 6, 9 and 12 after hematopoietic cell transplant. (Cohort A)

VI. To study the association of single cell mass cytometry that investigates B cell receptor signaling and its association with new acute or chronic graft-versus-host disease on B-cell receptor (BCR) signaling. (Cohort A)

OUTLINE:

Beginning between 60-90 days post donor stem cell transplant, patients receive ibrutinib orally (PO) once daily (QD) until 1 year post donor stem cell transplant in the absence of disease progression or unacceptable toxicity.

After completion of treatment, patients are followed up for 1 year.

Being tested
Ibrutinib, Laboratory Biomarker Analysis
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Follicular, Hodgkin Disease, Lymphoma, Mantle-Cell

What participants receive

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

  • IbrutinibDrug

    Given by mouth

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT02869633
Study groupRoleWhat they receive
Treatment (ibrutinib)ExperimentalBeginning between 60-90 days post donor stem cell transplant, patients receive ibrutinib PO QD until 1 year post donor stem cell 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. Progression Free Survival Probability at 12-month Post HCT

    The progression free survival (PFS) is defined as time to progression, or relapse of the underlying disease for which transplant was undertaken, or death from any non-relapse causes, starting from the date of stem cell transplant (SCT). This will be restricted to patients in cohort A which includes the diagnoses of CLL and MCL, only, and patients treated with ibrutinib. Twelve-month PFS probability with 95% confidence interval will be estimated using Kaplan-Meier method. This probability range between 0 and 1, and the higher the better.

    Measured: Time to progression, or relapse of the underlying disease for which transplant was undertaken, or death from any non-relapse causes, assessed 12 months post HCT.

Secondary outcomes (4)

  1. Minimal Residual Disease Assessed by Sequencing

    Measured: Up to 12 months

  2. T Cell Repertoire Assessed by IMMUNOSEQ

    Measured: Up to 12 months

  3. B Cell Subsets and Signaling Assessed by Mass Cytometry

    Measured: Up to 12 months

  4. T Cell Subsets and Signaling Assessed by Mass Cytometry

    Measured: Up to 12 months

Timeline

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

  1. First posted17 Aug 2016 (estimated)
  2. Study startNov 2016
  3. Primary completion18 Nov 2021
  4. Study completionOct 2023

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
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02869633
Sponsor's protocol ID
VICC CTT 1651
Other IDs
NCI-2016-01246
Status last verified
Oct 2023
First submitted
10 Aug 2016
Last updated
23 Oct 2023
Data monitoring committee
Yes
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ibrutinib and Laboratory Biomarker Analysis in people with Blastoid Variant Mantle Cell Lymphoma and Recurrent Chronic Lymphocytic Leukemia, run by Vanderbilt-Ingram Cancer Center at 5 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 34 inclusion and 29 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 23 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 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 20 Jan 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?

Progression Free Survival Probability at 12-month Post HCT (time frame: Time to progression, or relapse of the underlying disease for which transplant was undertaken, or death from any non-relapse causes, assessed 12 months post HCT.). 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 NCT02869633.

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 23 Oct 2023.

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