Recurrent Mantle Cell Lymphoma Clinical Trial
Official title:
A Phase I/II Trial of Rituximab, Bendamustine, and Obatoclax in Patients With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma
This phase I/II trial is studying the side effects and the best dose of obatoclax mesylate when given together with rituximab and bendamustine hydrochloride to see how well it works compared with rituximab and bendamustine hydrochloride alone in treating patients with relapsed or refractory non-Hodgkin lymphoma. Obatoclax mesylate may stop the growth of cancer cells by blocking some of the proteins needed for cell growth. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as bendamustine hydrochloride, also work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving obatoclax mesylate together with rituximab and bendamustine hydrochloride may kill more cancer cells
PRIMARY OBJECTIVES:
I. To determine the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of the
combination of obatoclax mesylate, rituximab, and bendamustine hydrochloride in patients
with relapsed or refractory, indolent, B-cell non-Hodgkin lymphoma (phase I).
II. To define the qualitative and quantitative toxicities of the combination of obatoclax
mesylate, rituximab, and bendamustine (phase I).
III. To detect an improvement in median progression-free survival (PFS) from 6 to 12 months
with the addition of obatoclax mesylate to rituximab and bendamustine hydrochloride in
patients with indolent B-cell non-Hodgkin lymphoma (phase II).
SECONDARY OBJECTIVES:
I. To determine the overall objective response rate to the combination of obatoclax
mesylate, rituximab, and bendamustine versus rituximab and bendamustine hydrochloride in
patients with relapsed or refractory, indolent, B-cell non-Hodgkin lymphoma.
II. To characterize two-year PFS of patients with indolent B-cell non-Hodgkin lymphoma
receiving obatoclax mesylate, rituximab, and bendamustine hydrochloride versus rituximab and
bendamustine hydrochloride.
III. To assess the pharmacokinetics of obatoclax mesylate in patients with relapsed or
refractory, indolent, B-cell non-Hodgkin lymphoma.
IV. To assess the pharmacokinetics of the combination of bendamustine hydrochloride and
obatoclax mesylate in patients with relapsed or refractory, indolent, B-cell non-Hodgkin
lymphoma.
V. To determine the effects of the combination of rituximab, bendamustine hydrochloride, and
obatoclax mesylate on histone-oligodeoxynucleotide (ODNA) and levels of activated Bax and
Bak pro-apoptotic proteins in peripheral blood mononuclear cells and bone marrow aspirate
specimens.
VI. To identify associations of genetic polymorphisms in drug-metabolizing enzymes,
transporters, or target genes with pharmacokinetics, pharmacodynamics, or clinical outcomes.
OUTLINE: This is a phase I, dose-escalation study of obatoclax mesylate followed by a
randomized phase II study.
PHASE I: Patients receive obatoclax mesylate IV over 3 hours on days 1-3, rituximab IV over
4-8 hours on day 1 (day 3 of course 1), and bendamustine hydrochloride IV over 30 minutes on
day 1-2 (day 2-3 of course 1). Treatment repeats every 28 days for a maximum of 6 courses in
the absence of disease progression or unacceptable toxicity.
PHASE II: Patients are stratified according to prior bendamustine hydrochloride (yes vs no).
Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive obatoclax mesylate IV over 3 hours on days 1-3, rituximab IV over
4-8 hours on day 1, and bendamustine hydrochloride IV over 30 minutes on days 1-2.
ARM II: Patients receive rituximab and bendamustine hydrochloride as in arm I.
In both arms, treatment repeats every 28 days for up to 6 courses in the absence of disease
progression or unacceptable toxicity.
Patients undergo blood and bone marrow sample collection at baseline and periodically during
study for pharmacokinetics, pharmacodynamic, and pharmacogenetic studies.
After completion of study therapy, patients are followed up every 3 months for 2 years and
then every 6 months for 3 years.
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Status | Clinical Trial | Phase | |
---|---|---|---|
Withdrawn |
NCT04635683 -
Lenalidomide, Umbralisib, and Ublituximab for the Treatment of Relapsed or Refractory Indolent Non-Hodgkin Lymphoma or Mantle Cell Lymphoma
|
Phase 1 | |
Completed |
NCT01527045 -
Donor Atorvastatin Treatment in Preventing Severe Acute GVHD After Nonmyeloablative Peripheral Blood Stem Cell Transplant in Patients With Hematological Malignancies
|
Phase 2 | |
Active, not recruiting |
NCT02153580 -
Cellular Immunotherapy Following Chemotherapy in Treating Patients With Recurrent Non-Hodgkin Lymphomas, Chronic Lymphocytic Leukemia, or B-Cell Prolymphocytic Leukemia
|
Phase 1 | |
Active, not recruiting |
NCT01955499 -
Lenalidomide and Ibrutinib in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
|
Phase 1 | |
Terminated |
NCT02109224 -
Ibrutinib in Treating Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma in Patients With HIV Infection
|
Phase 1 | |
Completed |
NCT01427881 -
Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies
|
Phase 2 | |
Completed |
NCT01233921 -
Palifermin in Preventing Chronic Graft-Versus-Host Disease in Patients Who Have Undergone Donor Stem Cell Transplant for Hematologic Cancer
|
N/A | |
Completed |
NCT01093586 -
Donor Umbilical Cord Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
|
Phase 2 | |
Terminated |
NCT00383565 -
FR901228 in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
|
Phase 2 | |
Completed |
NCT00253630 -
Vorinostat in Treating Patients With Low-Grade Non-Hodgkin's Lymphoma
|
Phase 2 | |
Completed |
NCT00078858 -
Mycophenolate Mofetil and Cyclosporine in Reducing Graft-Versus-Host Disease in Patients With Hematologic Malignancies or Metastatic Kidney Cancer Undergoing Donor Stem Cell Transplant
|
Phase 1/Phase 2 | |
Completed |
NCT00006473 -
Oxaliplatin in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
|
Phase 2 | |
Completed |
NCT00003196 -
Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed by Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma
|
N/A | |
Active, not recruiting |
NCT01318317 -
Genetically Engineered Lymphocyte Therapy After Peripheral Blood Stem Cell Transplant in Treating Patients With High-Risk, Intermediate-Grade, B-cell Non-Hodgkin Lymphoma
|
Phase 1/Phase 2 | |
Terminated |
NCT01678443 -
Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies
|
Phase 1 | |
Completed |
NCT01921387 -
Radiolabeled Monoclonal Antibody and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With High-Risk Lymphoid Malignancies
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT01815749 -
Genetically Modified T-cell Infusion Following Peripheral Blood Stem Cell Transplant in Treating Patients With Recurrent or High-Risk Non-Hodgkin Lymphoma
|
Phase 1 | |
Recruiting |
NCT04007029 -
Modified Immune Cells (CD19/CD20 CAR-T Cells) in Treating Patients With Recurrent or Refractory B-Cell Lymphoma or Chronic Lymphocytic Leukemia
|
Phase 1 | |
Completed |
NCT01267812 -
Bortezomib and Rituximab in Treating Patients With Mantle Cell Lymphoma Who Have Previously Undergone Stem Cell Transplantation
|
Phase 2 | |
Completed |
NCT01588015 -
Vaccine Therapy in Preventing Cytomegalovirus Infection in Patients With Hematological Malignancies Undergoing Donor Stem Cell Transplant
|
Phase 1 |