Clinical Trials Logo

Clinical Trial Summary

Prospective, multicenter, observational registry of myeloma patients undergoing hematopoietic progenitor cell mobilization for upfront autologous transplantation.


Clinical Trial Description

High dose therapy (HDT) and autologous hematopoietic cell transplantation (autoHCT) is considered standard therapy for younger, transplant eligible multiple myeloma (MM) patients. Mobilization of peripheral blood progenitor cells (PBPC) for HDT and autoHCT can be accomplished by using cytokines, most commonly granulocyte-colony stimulating factor (G-CSF), either alone or in combination with chemotherapy or plerixafor. Limitations of cytokine-only mobilization in myeloma: There is little consensus about the optimal method for PBPC mobilization in patients with MM, although there is a growing recognition of suboptimal mobilization outcomes of certain subgroups of myeloma patients mobilized with G-CSF alone. Within this context, the adverse impact of prior lenalidomide therapy on PBPC mobilization is well documented; with up to 40% of MM patients treated with lenalidomide-based induction chemotherapies not collecting ≥2 x 106 CD34+ cells/kg when mobilized with G-CSF alone. Chemomobilization in myeloma: In contrast, mobilization with chemotherapy (mostly cyclophosphamide) in addition to G-CSF has been shown to improve PBPC collection yield and reduce mobilization failure rates in comparison to G-CSF alone. Limited retrospective data suggest that cyclophosphamide may overcome the effects of prior lenalidomide exposure on PBPC mobilization in MM patients. Cyclophosphamide doses employed for mobilization of PBPC in MM patients in most reports have ranged from 1 gm/m2 up to 7 gm/m2. Several studies have assessed the relative impact of cyclophosphamide dose-intensity on PBPC mobilization in myeloma patients treated with conventional chemotherapy regimens. In general PBPC mobilization with high-dose cyclophosphamide (HD-CY) (7 gm/m2) plus G-CSF was found to be significantly more toxic, when compared to intermediate-dose cyclophosphamide (ID-CY) (3-4 gm/m2) and G-CSF, without any convincing evidence of superior efficacy. Studies comparing mobilization with ID-CY plus G-CSF with low-dose cyclophosphamide (LD-CY) (1-2 gm/m2) plus G-CSF, reported higher total CD34+ cell yield with ID-CY, but at the cost of higher toxicity. However, no significant difference in mobilization failure rates between the ID- and LD-CY mobilization has been reported. But these data might not be applicable to MM treated in the era of novel agents. Hamadani et al. compared the efficacy and toxicity of PBPC mobilization with G-CSF and either ID-CY or LD-CY, in MM patients receiving only novel induction regimens, and reported a more robust PBPC mobilization and significantly reduced the rates of mobilization failure with ID-CY in MM patients receiving modern inductions. Within the context of stem cell mobilization in MM patients treated with novel inductions, it appears that ID-CY and G-CSF may have a favorable risk/benefit ratio and can be considered a regimen with an optimal dose-intensity in order to assess the efficacy of novel mobilization regimens against cyclophosphamide-based mobilizing strategies. But these single center observations merit confirmation in large, multicenter datasets. Plerixafor-based mobilization in myeloma: Plerixafor is a small molecule that inhibits chemokine stromal cell derived factor 1-alpha from binding to CXC chemokine receptor 4, resulting in increased hematopoietic stem and progenitor cell migration into peripheral blood circulation. Plerixafor use in combination with G-CSF has resulted in significant improvements in the mobilization outcomes of MM patients. Despite the promising results of plerixafor and G-CSF for PBPC mobilization, the use of chemotherapy-based mobilization regimens remain standard practice in many transplant centers, driven in part due the costs associated with plerixafor based strategies. Chemomobilization vs. Plerixafor-based mobilization in myeloma: No randomized trials comparing chemomobilization vs. plerixafor plus G-CSF in patients with myeloma have been published. While a few retrospective studies have reported on the relative efficacy of cyclophosphamide-based mobilization against plerixafor and G-CSF, they included patients receiving either LD-CY or doses above 4mg/m2, contained patients with non-Hodgkin lymphoma (NHL), and likely included MM patients receiving conventional induction regimens. Awan et al. retrospectively compared that efficacy, toxicity and cost of PBPC mobilization with G-CSF and either ID-CY or plerixafor, in MM patients receiving only novel induction regimens. Compared to plerixafor, ID-CY use was associated with higher median peak peripheral blood CD34+ cell count (68/µL vs. 160/µL, p<0.001), and CD34+ cell yield on day 1 of collection (6.9 x 106/kg vs. 11.7 x 106/kg, p=<0.001). No patients in either group had mobilization failure. The total CD34+ cell yield was significantly higher in the ID-CY patients (median collection 16.6 x 106 cells/kg vs. 11.6 x 106 cells/kg; p-value <0.001). Mobilization with ID-CY was associated with significantly more frequent episodes of febrile neutropenia (16.3% vs. 0%; p=0.02), higher use of intravenous antibiotics (16.3% vs. 3%; p=0.03), transfusion support and need for hospitalizations (p=0.02). The average total cost of mobilization in the plerixafor group was significantly higher compared to the ID-CY group ($28,980 vs. $22,504.8; p-value=0.001). This study showed lower mobilization costs but greater toxicity with chemotherapy based mobilization in MM. The limitations of the analysis include small sample size and retrospective nature. Of note LD-CY in a different study was shown to be inferior to plerixafor in terms of PBPC mobilization efficacy and collection failure rates. As needed or Just-in-time Plerixafor: As noted previously, plerixafor combined with G-CSF provides superior mobilization outcomes in MM and NHL compared to G-CSF alone. It has also been shown to be an effective salvage option for patients failing to collect adequate CD34+ cells with G-CSF alone or chemomobilization [24-26]. However, the high cost of plerixafor has limited its routine use in HPC mobilization. Risk-adapted algorithms have been developed in several institutions to rescue patients at high-risk for mobilization failure and restrict plerixafor use to curtail mobilization costs. Veltri et al. recently reported a single institution comparative analysis of patients with MM and lymphoma who underwent G-CSF mobilization, with plerixafor used either routinely or as needed in patients at risk for mobilization failure. This analysis showed no mobilization failure events with either administering plerixafor routinely to all patients vs. by using a JIT approach, but showed that JIT method was associated with significantly lower collection costs. While it is clear that PBPC mobilization has been a subject of several reports, including a recent registry analysis, these reports are limited by their retrospective nature, small sample size, heterogeneity of patient population and often missing information on healthcare resource utilization. In the current large, multicenter, observational study the investigators intend to collect detailed information regarding patient, disease, mobilization and healthcare utilization characteristic in a prospective fashion. This prospective, mobilization, registry dataset would then be used to evaluate efficacy of various mobilization regimens, their cost, associated healthcare resource utilization and impact on post transplantation outcomes. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT03200626
Study type Observational
Source Medical College of Wisconsin
Contact
Status Completed
Phase
Start date June 1, 2017
Completion date October 31, 2022

See also
  Status Clinical Trial Phase
Recruiting NCT05027594 - Ph I Study in Adult Patients With Relapsed or Refractory Multiple Myeloma Phase 1
Completed NCT02412878 - Once-weekly Versus Twice-weekly Carfilzomib in Combination With Dexamethasone in Adults With Relapsed and Refractory Multiple Myeloma Phase 3
Completed NCT01947140 - Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies Phase 1/Phase 2
Recruiting NCT05971056 - Providing Cancer Care Closer to Home for Patients With Multiple Myeloma N/A
Recruiting NCT05243797 - Phase 3 Study of Teclistamab in Combination With Lenalidomide and Teclistamab Alone Versus Lenalidomide Alone in Participants With Newly Diagnosed Multiple Myeloma as Maintenance Therapy Following Autologous Stem Cell Transplantation Phase 3
Active, not recruiting NCT04555551 - MCARH109 Chimeric Antigen Receptor (CAR) Modified T Cells for the Treatment of Multiple Myeloma Phase 1
Recruiting NCT05618041 - The Safety and Efficay Investigation of CAR-T Cell Therapy for Patients With Hematological Malignancies N/A
Active, not recruiting NCT03844048 - An Extension Study of Venetoclax for Subjects Who Have Completed a Prior Venetoclax Clinical Trial Phase 3
Recruiting NCT03412877 - Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Neoantigens in People With Metastatic Cancer Phase 2
Completed NCT02916979 - Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic SCT Using FluBuATG Phase 1
Recruiting NCT03570983 - A Trial Comparing Single Agent Melphalan to Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) as a Preparative Regimen for Patients With Multiple Myeloma Undergoing High Dose Therapy Followed by Autologous Stem Cell Reinfusion Phase 2
Completed NCT03665155 - First-in- Human Imaging of Multiple Myeloma Using 89Zr-DFO-daratumumab, a CD38-targeting Monoclonal Antibody Phase 1/Phase 2
Terminated NCT03399448 - NY-ESO-1-redirected CRISPR (TCRendo and PD1) Edited T Cells (NYCE T Cells) Phase 1
Completed NCT02812706 - Isatuximab Single Agent Study in Japanese Relapsed AND Refractory Multiple Myeloma Patients Phase 1/Phase 2
Active, not recruiting NCT05024045 - Study of Oral LOXO-338 in Patients With Advanced Blood Cancers Phase 1
Active, not recruiting NCT03989414 - A Study to Determine the Recommended Dose and Regimen and to Evaluate the Safety and Preliminary Efficacy of CC-92480 in Combination With Standard Treatments in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) and Newly Diagnosed Multiple Myeloma (NDMM) Phase 1/Phase 2
Active, not recruiting NCT03792763 - Denosumab for High Risk SMM and SLiM CRAB Positive, Early Myeloma Patients Phase 2
Withdrawn NCT03608501 - A Study of Ixazomib, Thalidomide and Dexamethasone in Newly Diagnosed and Treatment-naive Multiple Myeloma (MM) Participants Non-eligible for Autologous Stem-cell Transplantation Phase 2
Recruiting NCT04537442 - Clinical Study to Evaluate the Safety and Efficacy of IM21 CAR-T Cells in the Treatment of Elderly Patients With Relapsed or Refractory Multiple Myeloma Phase 1
Completed NCT02546167 - CART-BCMA Cells for Multiple Myeloma Phase 1