Protocol Summary

Protocol No.: OCR15633

Sponsor Protocol No.: A051301; BMT CTN 1201

Study Title
A Randomized Double-Blind Phase III Study of Ibrutinib During and Following Autologous Stem Cell Transplantation Versus Placebo in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma of the Activated B-Cell Subtype

Principal Investigator(s)
Wingard, John

Objective
This randomized phase III trial studies ibrutinib to see how well it works compared to placebo when given before and after stem cell transplant in treating patients with diffuse large B-cell lymphoma that has returned after a period of improvement (relapsed) or does not respond to treatment (refractory). Before transplant, stem cells are taken from patients and stored. Patients then receive high doses of chemotherapy to kill cancer cells and make room for healthy cells. After treatment, the stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Ibrutinib is a drug that may stop the growth of cancer cells by blocking a protein that is needed for cell growth. It is not yet known whether adding ibrutinib to chemotherapy before and after stem cell transplant may help the transplant work better in patients with relapsed or refractory diffuse large B-cell lymphoma.

Description
After completion of treatment, patients are followed up periodically for 60 months from registration.

Phase: Phase III

Age Group: Adult

Scope: National

Treatment
CONDITIONING REGIMEN: Investigators may choose to use either the BEAMi or CBVi regimen.

BEAMi: Patients receive ibrutinib or placebo PO on days -6 to -1, carmustine IV over 2 hours on day -6, etoposide IV BID over 1-2 hours and cytarabine IV BID over 1-2 hours on days -5 to -2, and melphalan IV over 20-30 minutes on day -1.

CBVi: Patients receive ibrutinibor placebo PO on days -6 to -1, carmustine IV over 2 hours on day -6, etoposide IV over 4 hours on day -4, and cyclophosphamide IV on day -2.

TRANSPLANT: In both arms, patients undergo autologous hematopoietic progenitor cell or bone marrow transplant on day 0.

CONTINUATION REGIMEN: Beginning 30-36 days after transplant, patients receive ibrutinib or placebo PO on days 1-28. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

Patients randomized to placebo and experience disease progression may crossover the ibrutinib arm.

Detailed Eligibility
INCLUSION CRITERIA:
1. Ages 18 years old and older
2. Patients must have paraffin tissue from the diagnostic or relapse biopsy available to be submitted for central pathology review and integral molecular subtyping; this review is mandatory prior to registration to confirm eligibility and should be initiated as soon as possible; determination of cell-of-origin subtype will be performed using the lymphoma subtyping test (LST) assay
3. Diagnosis of World Health Organization (WHO) diffuse large B-cell lymphoma, high grade B-cell lymphoma not otherwise specified, or B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma
4. Determination of activated B-cell-like (ABC) subtype by pre-registration central review
5. Patient must be deemed eligible to proceed with high-dose chemotherapy and autologous stem cell transplantation by local transplant center
6. New York Heart Association class I or less; ordinary physical activity does not cause undue fatigue, palpitations, dyspnea, or angina pain; patients 60 years or older must have a left ventricular ejection fraction (LVEF) at rest >= 40% measured by echocardiogram or multi-gated acquisition (MUGA)
7. Diffusion capacity of the lung for carbon monoxide (DLCO) >= 40% of predicted (corrected for hemoglobin)
8. Forced expiratory volume in 1 second (FEV1) >= 40% of predicted (corrected for hemoglobin)
9. Forced vital capacity (FVC) >= 40% of predicted (corrected for hemoglobin)
10. Total Bilirubin =11. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =12. Creatinine == 40 mL/min by Cockcroft-Gault formula
13. Prothrombin time (PT)/ international normalized ration (INR) 14. Patient must have progressed or be refractory to prior anthracycline-containing chemotherapy (e.g. R-CHOP, DA-EPOCH-R, etc)
15. No more than 3 prior regimens for large cell component (e.g. one induction and two salvage therapies); monoclonal antibody alone or involved field/involved site radiotherapy do not count as lines of therapy
16. Prior use of ibrutinib is allowed unless patient has had disease progression while receiving ibrutinib
17. Patient must have chemosensitive disease as defined by at least a partial response to salvage therapy at their latest assessment
18. No major surgery =19. Not pregnant and not nursing; for women of childbearing potential only, a negative serum pregnancy test must be obtained within 14 days prior to registration
20. Women of childbearing potential must use adequate contraception from study start to one month after the last dose of protocol therapy; adequate contraception is defined as hormonal birth control, intrauterine device, double barrier method or total abstinence; men must practice complete abstinence or agree to use an adequate contraception method from study start to one month after the last dose of protocol therapy
21. Patients should not require chronic use of strong CYP3A inhibitors or strong CYP3A inducers
22. Patients should not require concurrent therapeutic doses of steroids (> 20 mg of prednisone/day or equivalent) unless they need them for the indications; steroids should be discontinued for 14 days before starting protocol treatment

** Contact study team for complete eligibility details

Applicable Disease Sites
Lymphoma - Non-Hodgkin

Participating Institutions
UF Gainesville : Meghan Vazquez

Contact
Meghan Vazquez, RN
Phone: +1 352-273-6843

Email: meghanvazquez@ufl.edu

More Information:
View study listing on ClinicialTrials.gov
http://www.clinicaltrials.gov/ct2/show/
NCT02443077