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A Phase II Study of Ibrutinib Plus Rituximab in Patients With Relapsed/Refractory Mantle Cell Lymphoma


Phase 2
18 Years
N/A
Not Enrolling
Both
Lymphoma

Thank you

Trial Information

A Phase II Study of Ibrutinib Plus Rituximab in Patients With Relapsed/Refractory Mantle Cell Lymphoma


Study Drug Administration:

If you are found to be eligible for this study, you will begin the first cycle of treatment
with ibrutinib and rituximab. Each cycle is 28 days.

Ibrutinib Administration:

Every day you will take 4 ibrutinib capsules with 1 cup (about 8 ounces) of water. You must
take all 4 capsules at about the same time every day, at least 30 minutes before eating or
at least 2 hours after a meal. Do not open the capsules or dissolve them.

If you miss a dose, you can take it up to 6 hours after the time you would have taken it. If
it is later than 6 hours, you should skip the dose and start taking the capsules at the same
time as usual the next day.

You will need to fill out diary cards with information about when you take ibrutinib. You
should bring the diary cards with you to appointments.

Rituximab Administration:

On Days 1, 8, 15, and 22 of Cycle 1, you will receive rituximab by vein. The first infusion
takes 6-8 hours. After that, infusions take about 4 hours.

You will then receive rituximab by vein over 4 hours on Day 1 of Cycles 3-8 and every other
cycle after that for up to 2 years.

For some patients, you may receive the rituximab dose over 2 days. Your doctor will tell you
if this is the best approach for you.

Study Visits:

On Day 1 of all cycles:

- You will have a physical exam.

- You will have a neurological exam.

- Blood (about 2 tablespoons) will be drawn for routine tests.

- You complete the questionnaire about your symptoms and their effects on your daily
living.

- If your doctor thinks it is needed, you will have a bone marrow biopsy and/or
aspiration to check the status of the disease.

- If the study doctor thinks it is needed, you will have a gastrointestinal endoscopy.

- If the study doctor thinks it is needed, you will have a PET/CT scan to check the
status of the disease.

- If you can become pregnant, you will have a blood (about 1½ tablespoons) or urine
pregnancy test.

On Days 8, 15, and 22 of Cycle 1, blood (about 2 tablespoons) will be drawn for routine
tests.

On Day 1 of Cycles 2, 4, 6, 8, 10, and 12, then every 3 cycles after that, if the study
doctor thinks it is needed, you will have a CT scan to check the status of the disease.

On Day 1 of Cycles 3, 5, 7 and so on:

- Blood (about 2 tablespoons) will be drawn for biomarker testing. Biomarkers are found
in the blood and may be related to your reaction to the study drug. This will be done
up to Cycle 23.

- Blood (about 2 tablespoons) will be drawn to check your immune system.

Length of Study:

You may continue taking the study drugs for as long as the doctor thinks it is in your best
interest. You will no longer be able to take the drug if the disease gets worse, if
intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over once you have completed follow-up.

End-of-Treatment Visit:

After you finish taking the study drugs:

- You will have a physical exam.

- You will have an EKG to check your heart function.

- Blood (about 5-7 tablespoons) will be drawn for routine tests, for biomarker testing,
for immune system testing, and to check the status of the disease.

- You will have a CT scan and/or x-ray to check the status of the disease.

- You will complete the questionnaire about your symptoms and their effects on your daily
living.

- If your doctor thinks it is needed, you will have a PET/CT scan and/or bone marrow
biopsy/aspiration to check the status of the disease.

- If your doctor thinks it is needed, you will have a gastrointestinal endoscopy.

- If you can become pregnant, you will have a blood (about 1½ tablespoons) or urine
pregnancy test.

Long Term Follow-Up:

After your end-of-treatment visit, you will be called every 3 months for 1 year and every 6
months after that to see how you are doing. These calls will take about 2-3 minutes.

If you stop the study drug and the disease has gotten better or is stable at the time you
stopped taking the study drug, blood will be drawn every month for 3 months, then every 2
months for 6 months, and then every 3 months after that to check the status of the disease.

This is an investigational study. Ibrutinib is not FDA approved or commercially available.
It is currently being used for research purposes only. Rituximab is FDA approved for the
treatment of non-Hodgkin's lymphoma and certain types of leukemia.

Up to 50 patients will take part in this multicenter study. All 50 will be enrolled at MD
Anderson.


Inclusion Criteria:



1. Confirmed diagnosis of mantle cell lymphoma with CD20 and cyclin D1 through Cyclin D3
positivity in tissue biopsy.

2. Patient has relapsed and or refractory MCL and must have received at least one prior
treatment regimen for their disease. Patient with leukemia phase (peripheral blood
involvement), leptomeningeal disease, cerebral spinal fluid (CSF) MCL, central
nervous system (CNS) MCL, non-measurable disease, gastrointestinal (GI) MCL, or bone
marrow (BM) MCL are also eligible.

3. Understand and voluntarily sign an institutional review board (IRB)-approved informed
consent form.

4. Patient is age >/= 18 years at the time of signing the informed consent.

5. Patients with bone marrow or gastrointestinal (GI) only involvement are acceptable.

6. Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less

7. Absolute neutrophil count (ANC) >/= 750/mm^3, platelet count >/= 50,000/mm^3.
(Patients who have bone marrow infiltration by MCL are eligible if their ANC is >/=
500/mm^3 or their platelet level is equal to or > than 30,000/mm^3).

8. Aspartate transaminase (AST)[serum glutamic oxaloacetic transaminase (SGOT)] and
alanine transaminase (ALT) [serum glutamic pyruvic transaminase (SGPT)] < 2 x upper
limit of normal or < 5 x upper limit of normal if hepatic metastases are present.
Uric acid within normal limits. Serum bilirubin <1.5 mg/dl and Cr Clearance >/= 50
mL/min.

9. Patients must be willing to receive transfusions of blood products.

10. Willing and able to participate in all study related procedures and therapy including
swallowing capsules without difficulty.

Exclusion Criteria:

1. Any serious medical condition that 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, active hemorrhage,
laboratory abnormality or psychiatric illness.

2. Pregnant or breast feeding females.

3. 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 and is cleared by gastrointestinal (GI) consultation.

4. All patients with history of central nervous system lymphoma.

5. 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.

6. History of stroke or intracranial hemorrhage within 6 months prior to signing the
consent

7. 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.

8. Significant screening electrocardiogram (ECG) abnormalities including left bundle
branch block, 2nd degree AV block type II, 3rd degree block, bradycardia, or QTc >500
msec.

9. 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.

10. Prior chemotherapy within 3 weeks, nitrosoureas within 6 weeks, therapeutic
anticancer antibodies within 4 weeks, radio- or toxin-immunoconjugates within 10
weeks, radiation therapy or other investigational agents within 3 weeks, major
surgery within 4 weeks or vaccination with live attenuated vaccines within 4 weeks of
the first dose of study drug.

11. Prior treatment with ibrutinib.

12. Requires anticoagulation with warfarin or equivalent vitamin K antagonist.

13. Requires treatment with strong CYP3A4/5 inhibitors.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response Rate

Outcome Description:

Complete response (CR) and overall response rate (ORR) assessed by International Workshop Standardized Response Criteria for NHL, with secondary assessment of clinical benefit response. Toxicity defined as the following toxicities observed during cycle 1 (28 days) of the treatment: Study drug related grade 3 or higher non-hematologic toxicity Grade 4 hematologic toxicity (ANC < 0.5 X 10^9/L and Platelet count <25 X 10^9/L) Grade 3 neutropenia with elevated temperature (defined as ANC < 1.0 X 10^9/L and > 101 degrees F to be confirmed on two occasions). Inability to administer full schedule and dose of study therapy due to treatment related toxicity. Inability to receive scheduled Day 1 dose of Cycle 2 due to drug related toxicity persisting from Cycle 1 or drug related toxicity newly encountered on Day 1 of Cycle 2. Current regimen considered promising if OR rate at 8 weeks is at least 50% and toxicity rate at 4 weeks is below 30%.

Outcome Time Frame:

8 weeks

Safety Issue:

Yes

Principal Investigator

Michael Wang, MD, MS

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2013-0090

NCT ID:

NCT01880567

Start Date:

December 2013

Completion Date:

Related Keywords:

  • Lymphoma
  • Lymphoma
  • Relapsed/Refractory Mantle Cell Lymphoma
  • R/R MCL
  • Ibrutinib
  • PCI-32765
  • Rituximab
  • Rituxan
  • Lymphoma
  • Lymphoma, Mantle-Cell

Name

Location

University of Texas MD Anderson Cancer CenterHouston, Texas  77030