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CCND1 PositivePhase 2NCT03232307

Ibrutinib Plus Rituximab and Lenalidomide in Treating Elderly Participants With Newly Diagnosed Mantle Cell Lymphoma

A Phase 2 study testing Dexamethasone, Ibrutinib and Lenalidomide in people with CCND1 Positive and CD20-Positive Neoplastic Cells Present, run by M.D. Anderson Cancer Center.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This phase II trial studies how well ibrutinib plus rituximab and lenalidomide work in treating elderly participants with newly diagnosed mantle cell lymphoma. 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 66 years and older
What is being tested?
Dexamethasone, Ibrutinib and Lenalidomide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
1 Jul 2019to 1 Jul 2021
Phase
Phase 2
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 66 years and older
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • Confirmed diagnosis of MCL with CD20 and cyclin D1 positivity in tissue biopsy.
  • Ki-67 >= 50%.
  • Patients must have never received any prior systemic therapy for their disease.
  • 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 and are willing to participate in the study.
  • Patients should in general have bi-dimensional measurable disease using the Cheson criteria (measurable disease by computed tomography [CT] scan defined as at least 1 lesion that measures >= 1.5 cm in single dimension) (bone marrow or gastrointestinal [GI] only involvement is acceptable).
  • Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less.
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  • Absolute neutrophil count (ANC) >= 1000/mm^3 without transfusion support.
  • Platelet count > 100,000/mm^3. Patients who have bone marrow infiltration by MCL are eligible if their platelet level is >= 50,000 /mm^3 independent of platelet transfusions.
  • Aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) =< 3 x upper limit of normal.
  • Serum bilirubin < 1.5 mg/dl unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin.
  • Creatinine (Cr) clearance >= 25 mL/min (per Cockcroft-Gault equation).
  • Disease free of prior malignancies of equal to or greater than 6 months with exception of currently treated basal cell, squamous cell carcinoma of the skin, carcinoma "in situ" of the cervix or breast, or other malignancies in remission (including prostate cancer patients in remission from radiation therapy, surgery or brachytherapy), not actively being treated, with a life expectancy > 3 years.
  • Patients must be willing to receive transfusions of blood products.
  • Willing and able to participate in all study related procedures and therapy including swallowing capsules without difficulty.
  • Men must agree 1) to use a latex condom during sexual contact with a female of childbearing potential (FCBP) even if they have had a vasectomy from the time of signing the informed consent form through 90 days after the last dose of lenalidomide and ibrutinib; 2) to not donate sperm during and after the study. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10-14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide through 90 days and ibrutinib through 30 days after the last dose of study drug. FCBP must also agree to ongoing pregnancy testing.
  • All patients must be registered in and must comply with all requirements of the Revlimid Rems program.

Who cannot join

  • Any serious medical condition that, in the investigator opinion, places the patient at unacceptable risk and/or would prevent the subject from signing the informed consent form. Examples include but are not limited to, uncontrolled hypertension, uncontrolled diabetes mellitus, active/symptomatic coronary artery disease, active infection requiring treatment with intravenous (IV) antibiotics, antiviral or antifungal agents, active hemorrhage, or psychiatric illness in the investigator's opinion places the patient at unacceptable risk and would prevent the subject from signing the informed consent form.
  • Pregnant or breastfeeding females.
  • Known human immunodeficiency virus (HIV) infection. Patients with active hepatitis B infection (not including patients with prior hepatitis B vaccination; or positive serum hepatitis B antibody). Known hepatitis C infection is allowed as long as there is no active disease. These patients should be optimized by GI consultation for hepatitis B and infectious disease consult for hepatitis C.
  • The patient has a prior or concurrent malignancy that in the opinion of the investigator, presents a greater risk to the patient's health and survival, than of the MCL, within the subsequent 6 months at the time of consent.
  • History of stroke or intracranial hemorrhage within 6 months prior to signing the consent.
  • Patients at high-risk for thromboembolic disease, such as those with prior heterotopic ossification (h/o) deep venous thrombosis (DVT).
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  • Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure or myocardial infarction within 6 months at the time of consent or any class 3 (moderate) or 4 (severe) cardiac disease defined by the New York Heart Association classification.
  • Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular block (AV block) type II, 3rd degree block, bradycardia (< 50 beats per minute [bpm]), or corrected QT (QTc) > 500 msec.
  • Patients with persistent and uncontrolled atrial fibrillation even if rate controlled.
  • Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
  • Major surgery or wound that has not fully healed within 4 weeks or vaccination with live attenuated vaccines within 4 weeks of the first dose of study drugs.
  • Requires concomitant anticoagulation with warfarin or equivalent vitamin K antagonist.
  • Requires treatment with strong cytochrome P4503A (CYP3A) inhibitors.
  • All patients with central nervous system lymphoma.

About this study

Official title: A Phase II Study of Ibrutinib Plus Rituximab and Lenalidomide in Elderly Patients With Newly Diagnosed MCL

This phase II trial studies how well ibrutinib plus rituximab and lenalidomide work in treating elderly participants with newly diagnosed mantle cell lymphoma. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as rituximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ibrutinib plus rituximab and lenalidomide may work better in treating elderly participants with newly diagnosed mantle cell lymphoma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the overall response rate (ORR) at 4 months of ibrutinib plus rituximab and lenalidomide in elderly patients with newly-diagnosed, untreated mantle cell lymphoma (MCL).

SECONDARY OBJECTIVES:

  1. To evaluate the toxicity profile of the combination of ibrutinib plus rituximab and lenalidomide in newly diagnosed, untreated MCL.

II. To estimate the overall response rate (ORR); (partial response [PR] or better), the response duration (DOR), progression-free survival (PFS), time to progression (TTP) and overall survival (OS). Clinical benefit response [(CBR) = marginal response (MR) + ORR] will also be evaluated.

EXPLORATORY OBJECTIVES:

  1. Correlative studies will be aimed at confirming the mechanism of action of the combination and to identify predictors of response or resistance to therapy.

OUTLINE:

Participants receive ibrutinib orally (PO) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Participants also receive rituximab intravenously (IV) on days 1, 8, 15 and 22 in course 1 and 2, on day 1 of course 3-8, and then on day 1 of every other 28-day course, lenalidomide PO on days 1-21, and dexamethasone PO weekly. Treatment with rituximab repeats every 28 days for 2 years, with lenalidomide for 1 year, and with dexamethasone for up to 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up at 30 days, every 3 months for 1 year, and every 6 months thereafter.

Medical subject headings
Lymphoma, Mantle-Cell

What participants receive

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

  • DexamethasoneDrug

    Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex

    Given PO

  • IbrutinibDrug

    Also called BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

    Given PO

  • LenalidomideDrug

    Also called CC-5013, CC5013, CDC 501, Revlimid

    Given PO

  • RituximabBiological

    Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody

    Given IV

Study groups in NCT03232307
Study groupRoleWhat they receive
Treatment (ibrutinib, rituximab, lenalidomide, dexamethasone)ExperimentalParticipants receive ibrutinib PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Participants also receive rituximab IV on days 1, 8, 15 and 22 in course 1 and 2, on day 1 of course 3-8, and then on day 1 of every other 28-day course, lenalidomide PO on days 1-21, and dexamethasone PO weekly. Treatment with rituximab repeats every 28 days for 2 years, with lenalidomide for 1 year, and with dexamethasone for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Dexamethasone; Drug: Ibrutinib; Drug: Lenalidomide; Biological: Rituximab

What is being measured

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

  1. Overall response rate (ORR) per International Workshop Standardization Response Criteria for non-Hodgkin's lymphoma

    The overall response (complete response + partial response) at four months and toxicity at one month (during course 1) will be monitored simultaneously using the Bayesian approach of Thall, Simon, Estey as extended by Thall and Sung. Independence was assumed between or and toxicity, where toxicity is defined as dose-limiting toxicity (DLT) within cycle 1.

    Measured: At 4 months (each cycle is 28 days)

Secondary outcomes (3)

  1. Incidence of adverse events per Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.03

    Toxicity data by type and severity will be summarized by frequency tables. For the efficacy endpoints, intend-to-treat analysis will be performed. For the toxicity endpoint, per-treated analysis will be performed to include any patient who received the treatment regardless of the eligibility nor the duration or dose of the treatment received.

    Measured: At 1 month (cycle 1 is 28 days)

  2. Overall survival (OS)

    Summary statistics will be provided for continuous variables. Frequency tables will be used to summarize categorical variables. The distribution of time-to-event endpoints including overall survival and progression free survival will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test. Cox proportional hazard regression will be employed for multivariate analysis on time-to-event outcomes.

    Measured: Up to 4 years

  3. Progression-free survival

    Summary statistics will be provided for continuous variables. Frequency tables will be used to summarize categorical variables. The distribution of time-to-event endpoints including overall survival and progression free survival will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test. Cox proportional hazard regression will be employed for multivariate analysis on time-to-event outcomes.

    Measured: Up to 4 years

Timeline

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

  1. First posted27 Jul 2017
  2. Study start1 Jul 2019 (estimated)
  3. Primary completion1 Jul 2021 (estimated)
  4. Study completion1 Jul 2021 (estimated)

Why it stopped: Sponsor does not wish to proceed

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
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03232307
Sponsor's protocol ID
2016-0280
Other IDs
NCI-2018-01271, 2016-0280, P30CA016672
Status last verified
Aug 2019
First submitted
25 Jul 2017
Last updated
22 Aug 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dexamethasone, Ibrutinib and Lenalidomide in people with CCND1 Positive and CD20-Positive Neoplastic Cells Present, run by M.D. Anderson Cancer Center.

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 16 inclusion and 14 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: withdrawn, as of the sponsor's last update on 22 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

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?

The study was withdrawn before enrolling participants, so there are no results.

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?

Overall response rate (ORR) per International Workshop Standardization Response Criteria for non-Hodgkin's lymphoma (time frame: At 4 months (each cycle is 28 days)). 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 NCT03232307.

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 22 Aug 2019.

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