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
Overview
- Phase
- Phase 3
- Status
- Active, not recruiting
- Enrollment
- 94
- Locations
- 555
- Primary Endpoint
- 24-month Progression-free Survival (PFS), Defined as the Proportion of Patients Who Are Alive and Progression-free 2 Years From Randomization
Overview
Brief Summary
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.
Detailed Description
PRIMARY OBJECTIVE:
I. To evaluate the ability of ibrutinib to improve 24-month progression free survival (PFS) compared to placebo in patients with non-germinal center B-cell-like (GCB) diffuse large B-cell lymphoma (DLBCL) as determined by immunohistochemistry (IHC).
SECONDARY OBJECTIVES:
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.
CORRELATIVE SCIENCE OBJECTIVES:
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 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 DLBCL subtype based on the lymphoma subtyping test (LST) is associated with 24-month PFS, PFS, and OS with ibrutinib compared to placebo in patients treated on this protocol.
VIII. To assess whether activating mutations in the BCR pathway are associated with response to ibrutinib and with clinical outcomes in patients treated on this protocol.
IX. To assess whether there are any phenotypic associations with IHC markers (particularly MYC protein expression level) and presence of these mutations.
X. To assess whether BCL2, MYC, and Ki67 expression by IHC affect clinical outcomes in patients treated on this protocol.
XI. 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.
CONDITIONING REGIMEN:
ARM I: Investigators may choose to use either the BEAMi (carmustine, 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. Optionally, if a day of rest is planned, patients may receive BEAMi on days -7 to -2.
CBVi: Patients receive ibrutinib 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. Optionally, if a day of rest is planned, patients may receive CBVi on days -7 to -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.
CONTINUATION REGIMEN:
ARM I: Beginning 30-60 days after transplant, patients receive ibrutinib PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
ARM II: Beginning 30-60 days after transplant, patients receive placebo PO on days 1-28. Treatment repeats every 28 days for 12 cycles 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 every 6 months for up to 60 months from registration.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •PRE-REGISTRATION ELIGIBILITY CRITERIA (STEP 0)
- •Patients must have paraffin tissue from the diagnostic or relapse biopsy available to be submitted for central pathology review; this review is mandatory prior to registration to confirm eligibility and should be initiated as soon as possible
- •ELIGIBILITY CRITERIA (STEP 1)
- •Diagnosis of World Health Organization (WHO) diffuse large B-cell lymphoma, non-GCB by central review confirmation
- •Patient must be deemed eligible to proceed with high-dose chemotherapy and autologous stem cell transplantation by local transplant center
- •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)
- •Diffusion capacity of the lung for carbon monoxide (DLCO) \>= 40% of predicted (corrected or uncorrected for hemoglobin per institutional standards)
- •Forced expiratory volume in 1 second (FEV1) \>= 40% of predicted (corrected or uncorrected for hemoglobin per institutional standards)
- •Forced vital capacity (FVC) \>= 40% of predicted (corrected or uncorrected for hemoglobin per institutional standards)
- •Total bilirubin =\< 1.5 x upper limit of normal (ULN) unless isolated hyperbilirubinemia attributed to Gilbert's syndrome
Exclusion Criteria
- Not provided
Arms & Interventions
Arm I (ibrutinib, chemotherapy, autoHCT)
CONDITIONING REGIMEN: Investigators may choose to use either the BEAMi or CBVi regimen.
BEAMi: Patients receive ibrutinib PO on days -6 to -1 or days -7 to -2 if a day of rest is planned, 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 ibrutinib PO on days -6 to -1 or days -7 to -2 if a day of rest is planned, 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 30-60 days after transplant, patients receive ibrutinib PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Carmustine (Drug)
Arm I (ibrutinib, chemotherapy, autoHCT)
CONDITIONING REGIMEN: Investigators may choose to use either the BEAMi or CBVi regimen.
BEAMi: Patients receive ibrutinib PO on days -6 to -1 or days -7 to -2 if a day of rest is planned, 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 ibrutinib PO on days -6 to -1 or days -7 to -2 if a day of rest is planned, 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 30-60 days after transplant, patients receive ibrutinib PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Melphalan (Drug)
Arm II (placebo, chemotherapy, autoHCT)
CONDITIONING REGIMEN: Patients receive placebo PO on days -6 to -1 and receive 1 of the 2 conditioning regimens as in Arm I.
TRANSPLANT: Patients undergo autologous hematopoietic progenitor cell or bone marrow transplant on day 0.
CONTINUATION REGIMEN: Beginning 30-60 days after transplant, patients receive placebo PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may crossover Arm I.
Intervention: Autologous Hematopoietic Stem Cell Transplantation (Procedure)
Arm II (placebo, chemotherapy, autoHCT)
CONDITIONING REGIMEN: Patients receive placebo PO on days -6 to -1 and receive 1 of the 2 conditioning regimens as in Arm I.
TRANSPLANT: Patients undergo autologous hematopoietic progenitor cell or bone marrow transplant on day 0.
CONTINUATION REGIMEN: Beginning 30-60 days after transplant, patients receive placebo PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may crossover Arm I.
Intervention: Cytarabine (Drug)
Arm II (placebo, chemotherapy, autoHCT)
CONDITIONING REGIMEN: Patients receive placebo PO on days -6 to -1 and receive 1 of the 2 conditioning regimens as in Arm I.
TRANSPLANT: Patients undergo autologous hematopoietic progenitor cell or bone marrow transplant on day 0.
CONTINUATION REGIMEN: Beginning 30-60 days after transplant, patients receive placebo PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may crossover Arm I.
Intervention: Etoposide (Drug)
Arm II (placebo, chemotherapy, autoHCT)
CONDITIONING REGIMEN: Patients receive placebo PO on days -6 to -1 and receive 1 of the 2 conditioning regimens as in Arm I.
TRANSPLANT: Patients undergo autologous hematopoietic progenitor cell or bone marrow transplant on day 0.
CONTINUATION REGIMEN: Beginning 30-60 days after transplant, patients receive placebo PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may crossover Arm I.
Intervention: Melphalan (Drug)
Arm I (ibrutinib, chemotherapy, autoHCT)
CONDITIONING REGIMEN: Investigators may choose to use either the BEAMi or CBVi regimen.
BEAMi: Patients receive ibrutinib PO on days -6 to -1 or days -7 to -2 if a day of rest is planned, 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 ibrutinib PO on days -6 to -1 or days -7 to -2 if a day of rest is planned, 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 30-60 days after transplant, patients receive ibrutinib PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis (Other)
Arm II (placebo, chemotherapy, autoHCT)
CONDITIONING REGIMEN: Patients receive placebo PO on days -6 to -1 and receive 1 of the 2 conditioning regimens as in Arm I.
TRANSPLANT: Patients undergo autologous hematopoietic progenitor cell or bone marrow transplant on day 0.
CONTINUATION REGIMEN: Beginning 30-60 days after transplant, patients receive placebo PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may crossover Arm I.
Intervention: Laboratory Biomarker Analysis (Other)
Arm II (placebo, chemotherapy, autoHCT)
CONDITIONING REGIMEN: Patients receive placebo PO on days -6 to -1 and receive 1 of the 2 conditioning regimens as in Arm I.
TRANSPLANT: Patients undergo autologous hematopoietic progenitor cell or bone marrow transplant on day 0.
CONTINUATION REGIMEN: Beginning 30-60 days after transplant, patients receive placebo PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may crossover Arm I.
Intervention: Pharmacogenomic Study (Other)
Arm II (placebo, chemotherapy, autoHCT)
CONDITIONING REGIMEN: Patients receive placebo PO on days -6 to -1 and receive 1 of the 2 conditioning regimens as in Arm I.
TRANSPLANT: Patients undergo autologous hematopoietic progenitor cell or bone marrow transplant on day 0.
CONTINUATION REGIMEN: Beginning 30-60 days after transplant, patients receive placebo PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may crossover Arm I.
Intervention: Placebo Administration (Other)
Arm I (ibrutinib, chemotherapy, autoHCT)
CONDITIONING REGIMEN: Investigators may choose to use either the BEAMi or CBVi regimen.
BEAMi: Patients receive ibrutinib PO on days -6 to -1 or days -7 to -2 if a day of rest is planned, 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 ibrutinib PO on days -6 to -1 or days -7 to -2 if a day of rest is planned, 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 30-60 days after transplant, patients receive ibrutinib PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Etoposide (Drug)
Arm II (placebo, chemotherapy, autoHCT)
CONDITIONING REGIMEN: Patients receive placebo PO on days -6 to -1 and receive 1 of the 2 conditioning regimens as in Arm I.
TRANSPLANT: Patients undergo autologous hematopoietic progenitor cell or bone marrow transplant on day 0.
CONTINUATION REGIMEN: Beginning 30-60 days after transplant, patients receive placebo PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may crossover Arm I.
Intervention: Carmustine (Drug)
Arm I (ibrutinib, chemotherapy, autoHCT)
CONDITIONING REGIMEN: Investigators may choose to use either the BEAMi or CBVi regimen.
BEAMi: Patients receive ibrutinib PO on days -6 to -1 or days -7 to -2 if a day of rest is planned, 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 ibrutinib PO on days -6 to -1 or days -7 to -2 if a day of rest is planned, 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 30-60 days after transplant, patients receive ibrutinib PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Pharmacogenomic Study (Other)
Arm II (placebo, chemotherapy, autoHCT)
CONDITIONING REGIMEN: Patients receive placebo PO on days -6 to -1 and receive 1 of the 2 conditioning regimens as in Arm I.
TRANSPLANT: Patients undergo autologous hematopoietic progenitor cell or bone marrow transplant on day 0.
CONTINUATION REGIMEN: Beginning 30-60 days after transplant, patients receive placebo PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may crossover Arm I.
Intervention: Autologous Bone Marrow Transplantation (Procedure)
Arm I (ibrutinib, chemotherapy, autoHCT)
CONDITIONING REGIMEN: Investigators may choose to use either the BEAMi or CBVi regimen.
BEAMi: Patients receive ibrutinib PO on days -6 to -1 or days -7 to -2 if a day of rest is planned, 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 ibrutinib PO on days -6 to -1 or days -7 to -2 if a day of rest is planned, 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 30-60 days after transplant, patients receive ibrutinib PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Autologous Bone Marrow Transplantation (Procedure)
Arm I (ibrutinib, chemotherapy, autoHCT)
CONDITIONING REGIMEN: Investigators may choose to use either the BEAMi or CBVi regimen.
BEAMi: Patients receive ibrutinib PO on days -6 to -1 or days -7 to -2 if a day of rest is planned, 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 ibrutinib PO on days -6 to -1 or days -7 to -2 if a day of rest is planned, 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 30-60 days after transplant, patients receive ibrutinib PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Autologous Hematopoietic Stem Cell Transplantation (Procedure)
Arm I (ibrutinib, chemotherapy, autoHCT)
CONDITIONING REGIMEN: Investigators may choose to use either the BEAMi or CBVi regimen.
BEAMi: Patients receive ibrutinib PO on days -6 to -1 or days -7 to -2 if a day of rest is planned, 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 ibrutinib PO on days -6 to -1 or days -7 to -2 if a day of rest is planned, 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 30-60 days after transplant, patients receive ibrutinib PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Cyclophosphamide (Drug)
Arm II (placebo, chemotherapy, autoHCT)
CONDITIONING REGIMEN: Patients receive placebo PO on days -6 to -1 and receive 1 of the 2 conditioning regimens as in Arm I.
TRANSPLANT: Patients undergo autologous hematopoietic progenitor cell or bone marrow transplant on day 0.
CONTINUATION REGIMEN: Beginning 30-60 days after transplant, patients receive placebo PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression may crossover Arm I.
Intervention: Cyclophosphamide (Drug)
Arm I (ibrutinib, chemotherapy, autoHCT)
CONDITIONING REGIMEN: Investigators may choose to use either the BEAMi or CBVi regimen.
BEAMi: Patients receive ibrutinib PO on days -6 to -1 or days -7 to -2 if a day of rest is planned, 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 ibrutinib PO on days -6 to -1 or days -7 to -2 if a day of rest is planned, 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 30-60 days after transplant, patients receive ibrutinib PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Cytarabine (Drug)
Arm I (ibrutinib, chemotherapy, autoHCT)
CONDITIONING REGIMEN: Investigators may choose to use either the BEAMi or CBVi regimen.
BEAMi: Patients receive ibrutinib PO on days -6 to -1 or days -7 to -2 if a day of rest is planned, 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 ibrutinib PO on days -6 to -1 or days -7 to -2 if a day of rest is planned, 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 30-60 days after transplant, patients receive ibrutinib PO on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Ibrutinib (Drug)
Outcomes
Primary Outcomes
24-month Progression-free Survival (PFS), Defined as the Proportion of Patients Who Are Alive and Progression-free 2 Years From Randomization
Time Frame: Time between registration and disease progression or death, whichever comes first, assessed at 24 months
Will be assessed using the Lugano classification.
24-month Progression-free Survival (PFS), Defined as the Proportion of Patients Who Are Alive and Progression-free 2 Years From Randomization
Time Frame: Time between registration and disease progression or death, whichever comes first, assessed at 24 months
Will be assessed using the Lugano classification.
Secondary Outcomes
- Overall Survival (OS)(The time between randomization and death from any cause, assessed up to 5 years (60 months))
- Time to Hematopoietic Engraftment(First day of one week without platelet transfusion, assessed up to 5 years)
- PFS(Time between registration and disease progression or death, whichever comes first, assessed up to 5 years (60 months))
- Response Rate Using the Lugano Classification(Up to 60 months)
- Treatment-related Mortality(Up to 60 months)
- Incidence of Hematologic Toxicity of Ibrutinib Therapy(Up to 60 months)
- Incidence of Secondary Malignancies(Up to 60 months)
- Overall Survival (OS)(The time between randomization and death from any cause, assessed up to 5 years (60 months))
- Time to Hematopoietic Engraftment(First day of one week without platelet transfusion, assessed up to 5 years)
- PFS(Time between registration and disease progression or death, whichever comes first, assessed up to 5 years (60 months))
- Response Rate Using the Lugano Classification(Up to 60 months)
- Treatment-related Mortality(Up to 60 months)
- Incidence of Hematologic Toxicity of Ibrutinib Therapy(Up to 60 months)
- Incidence of Secondary Malignancies(Up to 60 months)