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Recurrent Adult Diffuse Large Cell LymphomaEarly Phase 1NCT01719250

Buparlisib in Treating Patients With Relapsed or Refractory Non-Hodgkin Lymphoma

A Early Phase 1 study testing Buparlisib, Laboratory Biomarker Analysis and Questionnaire Administration in people with Recurrent Adult Diffuse Large Cell Lymphoma and Recurrent Grade 3 Follicular Lymphoma, run by Mayo Clinic 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 pilot clinical trial studies how well buparlisib works in treating patients with non-Hodgkin lymphoma that has returned after a period of improvement or has not responded to previous treatment. Buparlisib 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?
Buparlisib, Laboratory Biomarker Analysis and Questionnaire Administration
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
1 siteUnited States
Study dates
Dec 2012to 22 Mar 2017
Phase
Early Phase 1
Are there results?
None posted in the registry

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

  • Biopsy-proven relapsed, refractory or residual aggressive B-cell non-Hodgkin lymphoma; NOTE: re-biopsy is necessary unless the patient has had a previous biopsy < 168 days prior to registration on this protocol and there has been no intervening treatment; eligible tumor types are diffuse large B-cell non-Hodgkin lymphoma (NHL), mantle cell lymphoma, transformed NHL, and follicular grade III
  • Not a candidate or has declined standard salvage therapy for their disease
  • Measurable disease as defined by at least ONE of the following:
  • Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) or the CT portion of the positron emission tomography (PET)/CT: must have at least one lesion that has a single diameter of >= 2 cm or tumor cells in the blood >= 5 x 10^9/L
  • Skin lesions can be used if the area is >= 2 cm in at least one diameter and photographed with a ruler
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
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  • Absolute neutrophil count (ANC) >= 1000/uL
  • Hemoglobin (Hgb) >= 9 g/dl
  • Platelets (PLT) >= 100,000/uL
  • Serum bilirubin within normal range (or =< 1.5 x upper limit of normal [ULN] if liver metastases are present; or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert syndrome)
  • Aspartate aminotransferase (AST) within normal limits or =< 3 x ULN if due to lymphoma
  • Serum creatinine =< 1.5 x ULN or 24-hour clearance >= 50 mL/min
  • Magnesium >= lower limit of normal (LLN)
  • Potassium >= LLN
  • Serum amylase =< ULN
  • Serum lipase =< ULN
  • Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L)
  • Serum calcium =< 10.9 mg/dL
  • Negative pregnancy test done =< 72 hours prior to starting drug, for women of childbearing potential only
  • Provide informed written consent
  • Willing to return to Mayo Clinic Rochester for follow-up
  • Willing to provide blood samples for correlative research purposes
  • Willingness to take BKM120 orally

Who cannot join

  • Any of the following:
  • Pregnant women
  • Nursing women
  • Women of childbearing potential who are unwilling to employ highly effective contraception during dosing with BKM120 and for 4 weeks after the final dose of treatment; NOTE: women of childbearing potential are defined as all women physiologically capable of becoming pregnant
  • Men of childbearing potential who are unwilling to employ highly effective contraception during dosing with BKM120 and for 16 weeks after the final dose of treatment and should not a father a child during this time; NOTE: men of childbearing potential are defined as all males physiologically capable of conceiving offspring
  • NOTE: the highly effective contraception is defined as either:
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  • True abstinence: when this is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
  • Sterilization: have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
  • Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate); for female subjects on the study, the vasectomized male partner should be the sole partner for that patient
  • Use of a combination of any two of the following (a+b):
  • Placement of an intrauterine device (IUD) or intrauterine system (IUS)
  • Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
  • Oral contraception, injected or implanted hormonal methods are not allowed
  • Uncontrolled infection
  • Average baseline of >= 4 stools per day
  • Therapy with myelosuppressive chemotherapy or biologic therapy < 21 days prior to registration unless the patient has recovered from the nadir of the previous treatment to a level that meets the inclusion eligibility criteria of this protocol
  • Patients who have received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) =< 5 effective half-lives prior to registration or who have not recovered from side effects of such therapy
  • Received wide field radiotherapy =< 28 days or limited field radiation for palliation =< 14 days prior to registration or who have not recovered from side effects of such therapy
  • Receiving corticosteroids > 10 mg of prednisone per day (or equivalent); NOTE: patients may be receiving stable doses of corticosteroids with a maximum dose of 10 mg of prednisone per day if they are being given for disorders other than lymphoma such as rheumatoid arthritis, polymyalgia rheumatica or adrenal insufficiency, or asthma
  • Persistent toxicities >= grade 2 from prior chemotherapy or biological therapy regardless of interval since last treatment
  • Active cardiac disease including any of the following:
  • Left ventricular ejection fraction (LVEF) < 45% as determined by multi gated acquisition (MUGA) scan or echocardiogram (ECHO)
  • Fridericia's corrected QT interval (QTcF) > 450 msec on screening electrocardiogram (ECG) (using the QTcF formula)
  • Unstable angina pectoris; patients with unstable angina should have angina controlled before entering the study
  • Ventricular arrhythmias except for benign premature ventricular contractions
  • Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication
  • Conduction abnormality requiring a pacemaker
  • Symptomatic pericarditis
  • Myocardial infraction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function
  • History of documented congestive heart failure (New York Heart Association functional classification III-IV)
  • Documented cardiomyopathy
  • Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation)
  • Known positivity for human immunodeficiency virus (HIV); note: baseline testing for HIV is not required
  • Active hepatitis B or C with uncontrolled disease; note: a detailed assessment of hepatitis B/C medical history and risk factors must be done at screening for all patients; hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) ribonucleic acid (RNA) polymerase chain reaction (PCR) testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior hepatitis B virus (HBV) infection
  • Other active malignancy requiring treatment that would interfere with the assessments of response of the lymphoma to protocol treatment
  • Inability to swallow or impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of the drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection) that would preclude use of oral medications
  • Any severe and/or uncontrolled medical conditions such as diabetes, poor lung function, or other conditions that, in the treating physician's opinion, could adversely impact their ability to participate in the study
  • Patients who have received prior treatment with a P13K inhibitor; patients with prior mammalian target of rapamycin (mTOR) inhibitor therapy are eligible
  • Using medications that have a strong risk of prolonging the QT interval or inducing torsades de pointes
  • Major surgery =< 14 days prior to registration or have not recovered from side effects of such therapy
  • Currently being treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5), (please note that co-treatment with weak inhibitors of cytochrome P450, family 3, subfamily A [CYP3A] is allowed)
  • Receiving certain fruits or herbal preparations/medications including, but are not limited to: St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, ginseng; fruits include the CYP3A inhibitors Seville oranges, grapefruit, pummelos, or exotic citrus fruits; NOTE: patients should stop using these fruits and herbal medications 7 days prior to first dose of study drug
  • Primary central nervous system (CNS) lymphoma or active metastases to the CNS; NOTE: active is defined as requiring therapy such as surgery, radiation, or chemotherapy =< 28 days of study registration or ongoing corticosteroid therapy for CNS disease
  • The following mood disorders as judged by the Investigator or a psychiatrist, or as a result of patient's mood assessment questionnaire:
  • Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others)
  • >= Common Terminology Criteria of Adverse Events (CTCAE) grade 3 anxiety
  • Meets the cut-off score of >= 12 in the Patient Health Questionnaire (PHQ)-9 or a cut-off of >= 15 in the Generalized Anxiety Disorder (GAD)-7 mood scale, respectively, or selects a positive response of "1, 2, or 3" to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9)
  • Treated with any hematopoietic colony-stimulating growth factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF]) =< 2 weeks prior to study registration; NOTE: erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to study registration, may be continued

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: A Pilot Study of the PI3K Inhibitor BKM120 in Patients With Relapsed Lymphoma

This pilot clinical trial studies how well buparlisib works in treating patients with non-Hodgkin lymphoma that has returned after a period of improvement or has not responded to previous treatment. Buparlisib 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 clinical benefit rate (complete response [CR], partial response [PR] or standard disease [SD] >= 6 months) with BKM120 (buparlisib) in patients with relapsed or refractory lymphoma.

SECONDARY OBJECTIVES:

  1. To evaluate overall response rate, overall survival, progression-free survival and duration of response.

II. To describe the toxicities associated with BKM120 in lymphoma. III. To evaluate prognostic factors for aggressive lymphoma and whether there's a correlation with clinical benefit.

TERTIARY OBJECTIVES:

  1. To assess serum cytokines before and after BKM120 therapy. II. To assess phosphatidylinositol 3-kinase (PI3K) pathway member expression on paraffin-embedded tumor samples pre-treatment.

III. To assess on paired fresh tumor tissue obtained from consenting patients pre- and post-therapy the change in activation of PI3K pathway members.

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

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

Being tested
Buparlisib, Laboratory Biomarker Analysis, Questionnaire Administration
Medical subject headings
Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Lymphoma, Mantle-Cell

What participants receive

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

  • BuparlisibDrug

    Also called BKM120, PI3K Inhibitor BKM120

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT01719250
Study groupRoleWhat they receive
Treatment (buparlisib)ExperimentalPatients receive buparlisib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Buparlisib; Other: Laboratory Biomarker Analysis; Other: Questionnaire Administration

What is being measured

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

  1. Clinical benefit defined as a PR or CR as the objective status at any time or an objective status of SD for a duration of greater than 6 months from registration

    The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent binomial confidence intervals for the true success proportion will be calculated.

    Measured: From 6 months from registration up to 1 year

Secondary outcomes (5)

  1. Duration of response

    If an adequate number of events are seen, the distribution of duration of response will be estimated using the method of Kaplan-Meier. Otherwise, duration of response will be summarized descriptively.

    Measured: From the date at which the patient's objective status is first noted to be a CR or PR to the earliest date progression is documented, assessed up to 1 year

  2. Overall response rate estimated by the number of confirmed responses (PR or CR) observed in the trial divided by the total number of evaluable patients

    Exact binomial 95% confidence intervals for the true overall response rate will be calculated.

    Measured: Up to 1 year

  3. Prognostic factors for aggressive lymphoma

    Will be summarized and used to help characterize the types of patients accrued to this trial. These classifications will be correlated with clinical benefit using Fisher's exact or Wilcoxon rank sum tests.

    Measured: Up to 1 year

  4. Progression-free survival time

    Will be estimated using the method of Kaplan-Meier.

    Measured: Time from registration to progression or death due to any cause, assessed up to 1 year

  5. Survival time

    Will be estimated using the method of Kaplan-Meier.

    Measured: Time from registration to death due to any cause, assessed up to 1 year

Timeline

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

  1. First posted1 Nov 2012 (estimated)
  2. Study startDec 2012
  3. Primary completion16 Sep 2016
  4. Study completion22 Mar 2017

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
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01719250
Sponsor's protocol ID
MC1183
Other IDs
NCI-2012-01582, MC1183, P30CA015083
Status last verified
Oct 2018
First submitted
30 Oct 2012
Last updated
9 Oct 2018
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Buparlisib, Laboratory Biomarker Analysis and Questionnaire Administration in people with Recurrent Adult Diffuse Large Cell Lymphoma and Recurrent Grade 3 Follicular Lymphoma, run by Mayo Clinic 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 23 inclusion and 48 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 9 Oct 2018. 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?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Clinical benefit defined as a PR or CR as the objective status at any time or an objective status of SD for a duration of greater than 6 months from registration (time frame: From 6 months from registration up to 1 year). 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 NCT01719250.

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 9 Oct 2018.

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