a study on Lymphoma
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.
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
I. To evaluate the ability of ibrutinib to improve 24-month progression free survival (PFS) compared to placebo.
I. To evaluate the ability of ibrutinib to improve overall survival (OS) compared to placebo.
II. To evaluate the ability of ibrutinib to improve progression free survival (PFS) compared to placebo.
III. To evaluate the ability of ibrutinib to improve post-transplant response rates compared to placebo.
IV. To evaluate time to hematopoietic recovery in the two arms. V. To evaluate the safety and tolerability of ibrutinib compared to placebo. VI. To evaluate the incidence of secondary malignancies in the two arms. VII. To evaluate immune reconstitution in the two arms.
I. To assess whether pre-autologous hematopoietic stem cell transplantation (AutoHCT) positive fludeoxyglucose F-18 (FDG)-positron emission tomography (PET) is associated with inferior 24-month PFS as well as PFS and OS.
II. To assess whether pre-AutoHCT FDG-PET results are differentially associated with 24-month PFS, PFS and OS in the ibrutinib versus placebo arms.
III. To evaluate the application of the Lugano criteria and change in quantitative measurements between pre-AutoHCT and post AutoHCT (e.g. delta standard uptake variable [SUV], %SUV decline and %metabolic tumor volume [MTV] decline, and other available applicable quantitative measurements) to assess the association between changes in these variables and outcomes, such as PFS and OS.
IV. To assess whether the glutathione S-transferase theta 1 (GSTT1) null polymorphism is correlated with pulmonary toxicity after BCNU (carmustine)-containing conditioning regimens as part of autologous stem cell transplantation.
V. To assess whether other polymorphisms in the BCNU metabolism pathway or BCNU damage repair pathway(s) are associated with pulmonary toxicity after BCNU-containing conditioning regimens as part of autologous stem cell transplantation.
VI. To evaluate whether any of the proposed deoxyribonucleic acid (DNA) polymorphisms are associated with other toxicities.
VII. To assess whether activating mutations in the breakpoint cluster region (BCR) pathway are associated with response to ibrutinib and with clinical outcomes in patients treated on this protocol.
VIII. To assess whether there are any phenotypic associations with immunohistochemistry (IHC) markers (particularly v-myc avian myelocytomatosis viral oncogene homolog [MYC] protein expression level) and presence of these mutations.
IX. To assess whether B-cell chronic lymphocytic leukemia (CLL)/lymphoma 2 (BCL2), MYC, and antigen Ki67 (Ki67) expression by IHC affect clinical outcomes in patients treated on this protocol.
X. To assess whether translocations in MYC with or without BCL2 and BC6 have poor outcomes in patients treated on this protocol and whether ibrutinib modifies the prognosis.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Investigators may choose to use either the BEAMi (camustine, etoposide, cytarabine, melphalan, ibrutinib) or CBVi (cyclophosphamide, carmustine, etoposide, ibrutinib) regimen.
BEAMi: Patients receive ibrutinib orally (PO) on days -6 to -1, carmustine intravenously (IV) over 2 hours on day -6, etoposide IV twice daily (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 carmustine IV over 2 hours on day -6, etoposide IV over 4 hours on day -5 to -3 and cyclophosphamide IV on day -2.
ARM II: Patients receive placebo PO on days -6 to -1 and receive 1 of the 2 conditioning regimens as in Arm I.
TRANSPLANT: In both arms, patients undergo autologous hematopoietic progenitor cell or bone marrow transplant on day 0.
ARM I: Beginning 30-36 days after transplant, patients receive ibrutinib PO on days 1-28. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
ARM II: Beginning 30-36 days after transplant, patients receive placebo PO on days 1-28. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may crossover Arm I.
After completion of treatment, patients are followed up periodically for 60 months from registration.
Activated B-Cell-Like Diffuse Large B-Cell Lymphoma B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma Diffuse Large B-Cell Lymphoma, Not Otherwise Specified Recurrent Diffuse Large B-Cell Lymphoma Refractory Diffuse Large B-Cell Lymphoma Etoposide Podophyllotoxin Etoposide phosphate Cytarabine Cyclophosphamide Melphalan Carmustine Mechlorethamine Nitrogen Mustard Compounds
For people ages 18 years and up
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