NCT01163357

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

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
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

• Autologous Hematopoietic Stem Cell Transplant Recipient
• Loss of Chromosome 17p
• Plasma Cell Leukemia
• Recurrent Plasma Cell Myeloma
• Refractory Plasma Cell Myeloma

Interventions

Type	Name	Description
DRUG	bortezomib	Given IV
DRUG	fludarabine phosphate	Given IV
OTHER	melphalan	Given IV
RADIATION	total marrow irradiation	Undergo TMI
DRUG	tacrolimus	Given IV and orally
DRUG	sirolimus	Given orally
PROCEDURE	peripheral blood stem cell transplantation	Undergo allogeneic PBSC transplant
OTHER	laboratory biomarker analysis	Correlative studies

Timeline

• Start date: 2011-01-28
• Primary completion: 2019-07-20
• Completion: 2024-05-20
• First posted: 2010-07-15
• Last updated: 2025-03-26

Locations

1 site across 1 country: United States