Recurrent Plasma Cell Myeloma Clinical Trial
Official title:
Randomized Study of Personalized Melphalan Dosing in the Setting of Autologous Transplant
This randomized phase II trial studies the side effects and how well melphalan hydrochloride works in treating patients with multiple myeloma that has come back or does not respond to treatment. Drugs used in chemotherapy, such as melphalan hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
PRIMARY OBJECTIVES:
I. Identify whether targeting approximate (approx.) 3- or 5-days of severe neutropenia after
exposure to a personalized melphalan hydrochloride (melphalan) dose results in best clinical
outcome.
II. Measure melphalan-related toxicities in both 3-day and 5-day arms. III. Measure response
per International Myeloma Working Group (IMWG). IV. Record overall survival (OS) and
progression free survival (PFS).
SECONDARY OBJECTIVES:
I. To administer a test dose of melphalan and obtain test dose melphalan pharmacokinetics
(PK) data from the first 33 patients.
II. Measure drug-induced deoxyribonucleic acid (DNA) damage in peripheral blood mononuclear
cells (PBMCs) treated with melphalan ex vivo post exposure.
III. Measure drug-induced DNA damage in patient myeloma cells treated with melphalan ex vivo.
IV. Assess melphalan-induced DNA damage in treated patients. V. Measure allele and genotype
frequencies of variants, as well as gene expression of XRCC1 rs25487 and XRCC3 rs861529.
VI. Additional genetic variants relevant to DNA repair, melphalan transport, and clinical
toxicities may be tested as well.
VII. Test cytotoxicity (half maximal inhibitory concentration [IC50]) of patient PBMCs prior
to autologous transplant after exposure to melphalan ex vivo.
VIII. Measure p53 and phospho(TP53) in patient PBMCs prior to autologous transplant at
baseline and after exposure to melphalan ex vivo.
IX. Incorporate both disease progression and drug-related toxicities into separate models
linked to our calculated melphalan area under the curve (AUC) model.
OUTLINE: Patients are randomized into 1 of 2 arms.
ARM I: Patients receive personalized dose of melphalan hydrochloride intravenously (IV) on
day -2 for predicted 3-day duration of severe neutropenia and undergo standard of care
autologous stem cell transplant on day 0.
ARM II: Patients receive personalized dose of melphalan hydrochloride IV on day -2 for
predicted 5-day duration of severe neutropenia and undergo standard of care autologous stem
cell transplant on day 0.
After completion of study treatment, patients are followed up for 30 days, at 3 months after
transplant, and then every 6-12 months.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT02948283 -
Metformin Hydrochloride and Ritonavir in Treating Patients With Relapsed or Refractory Multiple Myeloma or Chronic Lymphocytic Leukemia
|
Phase 1 | |
Terminated |
NCT04956302 -
Panobinostat in Combination With Daratumumab, Bortezomib and Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma
|
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 | |
Completed |
NCT01689987 -
Hydroxychloroquine, Cyclophosphamide, Dexamethasone, and Sirolimus in Treating Patients With Relapsed or Refractory Multiple Myeloma
|
Phase 1 | |
Completed |
NCT02506959 -
Panobinostat, Gemcitabine Hydrochloride, Busulfan, and Melphalan Before Stem Cell Transplant in Treating Patients With Refractory or Relapsed Multiple Myeloma
|
Phase 2 | |
Active, not recruiting |
NCT03457142 -
Abatacept, Ixazomib Citrate, and Dexamethasone in Treating Patients With Multiple Myeloma Resistant to Chemotherapy
|
Phase 2 | |
Recruiting |
NCT03246906 -
Comparison of Triple GVHD Prophylaxis Regimens for Nonmyeloablative or Reduced Intensity Conditioning Unrelated Mobilized Blood Cell Transplantation
|
Phase 2 | |
Active, not recruiting |
NCT02765854 -
Ixazomib and Dexamethasone Versus Ixazomib, Dexamethasone and Lenalidomide, Randomized With NFKB2 Rearrangement
|
Phase 2 | |
Recruiting |
NCT05514990 -
Bortezomib and Pembrolizumab With or Without Pelareorep for the Treatment of Relapsed or Refractory Multiple Myeloma, AMBUSH Trial
|
Phase 1/Phase 2 | |
Completed |
NCT01989598 -
Trametinib and Akt Inhibitor GSK2141795 in Treating Patients With Relapsed or Refractory Multiple Myeloma
|
Phase 2 | |
Completed |
NCT03605719 -
Dexamethasone, Carfilzomib, & Nivolumab With Pelareorep for Relapsed/Refractory Multiple Myeloma
|
Phase 1 | |
Completed |
NCT01903811 -
S1304, Carfilzomib and Dexamethasone for Treating Patients With Relapsed or Refractory Myeloma
|
Phase 2 | |
Recruiting |
NCT05391750 -
Venetoclax and Tocilizumab for the Treatment of Patients With Relapsed or Refractory t(11;14) Multiple Myeloma
|
Phase 1 | |
Completed |
NCT00789776 -
Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation, and Donor Bone Marrow Transplant Followed by Donor Natural Killer Cell Therapy, Mycophenolate Mofetil, and Tacrolimus in Treating Patients With Hematologic Cancer
|
Phase 1/Phase 2 | |
Completed |
NCT02593123 -
Adoptive Immunotherapy in Relapsed Hematological Malignancy: Early GVHD Prophylaxis
|
Phase 2 | |
Terminated |
NCT04407442 -
Daratumumab, Azacitidine, and Dexamethasone for Treatment of Patients With Recurrent or Refractory Multiple Myeloma Previously Treated With Daratumumab
|
Phase 2 | |
Completed |
NCT00450814 -
Vaccine Therapy With or Without Cyclophosphamide in Treating Patients With Recurrent or Refractory Multiple Myeloma
|
Phase 1/Phase 2 | |
Completed |
NCT03338972 -
Immunotherapy With BCMA CAR-T Cells in Treating Patients With BCMA Positive Relapsed or Refractory Multiple Myeloma
|
Phase 1 | |
Recruiting |
NCT04508790 -
Leflunomide, Pomalidomide, and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma
|
Phase 2 | |
Recruiting |
NCT05363111 -
Radioimmunotherapy (111Indium/225Actinium-DOTA-daratumumab) for the Treatment of Relapsed/Refractory Multiple Myeloma
|
Phase 1 |