Ignite Creation Date:
2025-12-24 @ 6:38 PM
Ignite Modification Date:
2025-12-27 @ 6:37 AM
Study NCT ID:
NCT01163357
Status:
COMPLETED
Last Update Posted:
2025-03-26
First Post:
2010-07-14
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Bortezomib, Total Marrow Irradiation, Fludarabine Phosphate, and Melphalan in Treating Patients Undergoing Donor Peripheral Blood Stem Cell Transplant For High-Risk Stage I or II Multiple Myeloma
Sponsor:
City of Hope Medical Center
Organization:
Study Overview
Official Title:
Phase I Study of Bortezomib With or Without Total Marrow Irradiation (TMI) Using Intensity Modulated Radiation Therapy (IMRT) in Combination With Fludarabine (FLU) and Melphalan (MEL) as a Preparative Regimen for Allogeneic Hematopoietic Stem Cell (HSC) Transplantation in Patients With High Risk Multiple Myeloma
Status:
COMPLETED
Status Verified Date:
2025-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving chemotherapy drugs, such as fludarabine phosphate and melphalan, and total marrow irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.
PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given together with fludarabine phosphate and melphalan with or without total marrow irradiation in treating patients undergoing donor peripheral blood stem cell transplant for high-risk stage I or II multiple myeloma.
PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given together with fludarabine phosphate and melphalan with or without total marrow irradiation in treating patients undergoing donor peripheral blood stem cell transplant for high-risk stage I or II multiple myeloma.
Detailed Description:
PRIMARY OBJECTIVES:
I. To determine the feasibility of escalating doses of bortezomib with or without total marrow irradiation (TMI) at a fixed dose of 900 cGy in combination with fludarabine (FLU) and melphalan (MEL) as preparative regimen for allogeneic hematopoietic stem cell transplant in patients with high risk multiple myeloma who have human leukocyte antigen (HLA) matched donor (sibling or matched unrelated donor).
II. To describe toxicities, maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of this preparative regimen.
SECONDARY OBJECTIVES:
I. To evaluate the frequency of clinical response, i.e., complete response \[CR\], partial response \[PR\], very good partial response \[VGPR\]) at 6 month and 1 year post transplant.
II. To evaluate the frequency of primary and secondary engraftment failure.
III. To evaluate the time to neutrophil and platelet engraftment.
IV. To evaluate the incidence of acute and chronic graft-versus-host disease (GVHD).
V. To evaluate progression-free survival.
VI. To evaluate overall survival.
VII. To evaluate minimal residual disease (MRD) at 6 months and 1 year post transplant by flow cytometry in the bone marrow.
OUTLINE: This is a dose-escalation study of bortezomib. Patients are assigned to 1 of 2 treatment groups. GROUP I (patients eligible for TMI): Patients receive fludarabine phosphate intravenously (IV) on days -9 to -5 and melphalan IV on day -4. Patients also undergo TMI twice daily (BID) on days -9 to -7. If no DLT is observed in the first cohort, bortezomib IV will be added on days -6 and -3 for subsequent cohorts. GROUP II (patients ineligible for TMI): Patients receive fludarabine phosphate IV and melphalan IV as in Group I. Patients also receive bortezomib IV on days -6, -3, 1, and 4.
TRANSPLANT: All patients undergo allogeneic peripheral blood stem cell (PBSC) transplant on day 0.
GVHD PROPHYLAXIS: All patients receive tacrolimus IV or orally (PO) and sirolimus PO beginning on day -3.
After completion of study treatment, patients are followed up at day 100, 6 months, and then annually thereafter for up to 4 years.
I. To determine the feasibility of escalating doses of bortezomib with or without total marrow irradiation (TMI) at a fixed dose of 900 cGy in combination with fludarabine (FLU) and melphalan (MEL) as preparative regimen for allogeneic hematopoietic stem cell transplant in patients with high risk multiple myeloma who have human leukocyte antigen (HLA) matched donor (sibling or matched unrelated donor).
II. To describe toxicities, maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of this preparative regimen.
SECONDARY OBJECTIVES:
I. To evaluate the frequency of clinical response, i.e., complete response \[CR\], partial response \[PR\], very good partial response \[VGPR\]) at 6 month and 1 year post transplant.
II. To evaluate the frequency of primary and secondary engraftment failure.
III. To evaluate the time to neutrophil and platelet engraftment.
IV. To evaluate the incidence of acute and chronic graft-versus-host disease (GVHD).
V. To evaluate progression-free survival.
VI. To evaluate overall survival.
VII. To evaluate minimal residual disease (MRD) at 6 months and 1 year post transplant by flow cytometry in the bone marrow.
OUTLINE: This is a dose-escalation study of bortezomib. Patients are assigned to 1 of 2 treatment groups. GROUP I (patients eligible for TMI): Patients receive fludarabine phosphate intravenously (IV) on days -9 to -5 and melphalan IV on day -4. Patients also undergo TMI twice daily (BID) on days -9 to -7. If no DLT is observed in the first cohort, bortezomib IV will be added on days -6 and -3 for subsequent cohorts. GROUP II (patients ineligible for TMI): Patients receive fludarabine phosphate IV and melphalan IV as in Group I. Patients also receive bortezomib IV on days -6, -3, 1, and 4.
TRANSPLANT: All patients undergo allogeneic peripheral blood stem cell (PBSC) transplant on day 0.
GVHD PROPHYLAXIS: All patients receive tacrolimus IV or orally (PO) and sirolimus PO beginning on day -3.
After completion of study treatment, patients are followed up at day 100, 6 months, and then annually thereafter for up to 4 years.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2010-01610 | OTHER | NCI CTRP | View |