Melphalan+Bortezomib as a Conditioning Regimen for Autologous and Allogeneic Stem Cell Transplants in Multiple Myeloma

NCT ID: NCT00948922

Last Updated: 2019-09-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 124 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-18
• Study Completion Date: 2019-05-14

Brief Summary

The purpose of this study is to evaluate the effectiveness of Bortezomib when added to standard chemotherapy medicine(s) for treatment of Multiple Myeloma.

Detailed Description

The primary objectives of this study are:

• To determine the 2 year-progression free survival in multiple myeloma with an allogeneic transplant using a conditioning regimen of melphalan + fludarabine + Bortezomib in patients < 60 years of age and available HLA-matched donor and compare it with the 2 year-progression-free-survival after an autologous stem cell transplant with melphalan+Bortezomib conditioning in patients < 60 years.
• To determine the 2 year-progression free survival in multiple myeloma with an autologous stem cell transplant using a conditioning regimen of melphalan + Bortezomib. for patients > 60 years of age and patients < 60 years of age who decline allogeneic stem cell transplant.

The secondary objectives of this study are:

• To determine the overall survival in multiple myeloma with autologous or allogeneic stem cell transplants using the above conditioning regimens
• To determine the response rates in multiple myeloma using the above regimens.
• To determine minimal residual disease status using allele specific oligonucleotides (ASO-PCR) by PCR and flow-cytometry for multiple myeloma cells.
• To correlate minimal residual disease status with 2 year progression free survival and overall survival.
• To determine the incidence of acute and chronic graft-versus-host disease (GVHD) in multiple myeloma with allogeneic stem cell transplant using the above conditioning regimen.
• To examine quality of life in patients treated with allogeneic and autologous stem cell transplants using the above conditioning regimen.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A: Allogeneic Stem Cell Transplant

Allogeneic Stem Cell Transplant: Fludarabine+Melphalan+Bortezomib followed by Allogeneic Rescue.

Group Type: OTHER

Bortezomib

Intervention Type: DRUG

AUTOLOGOUS ARM: Day -3 bortezomib (1.3 mg/m\^2) as an intravenous push over 3 to 5 seconds (follows Melphalan infusion). ALLOGENEIC ARM: Day -3 bortezomib (1.3 mg/m\^2) as an intravenous push over 3 to 5 seconds (follows fludarabine and melphalan infusion).

Melphalan

Intervention Type: DRUG

AUTOLOGOUS ARM: Day -4 and Day -3 Melphalan 100 mg/m\^2/day IV over 30 minutes. ALLOGENEIC ARM: Day -4, Day -3 Melphalan 70 mg/m\^2/day IV over 30 minutes.

Fludarabine

Intervention Type: DRUG

Days -6,-5,-4,-3 Fludarabine 30 mg/m\^2/day IV

Allogeneic Stem Cell Transplant

Intervention Type: PROCEDURE

Allogeneic Stem Cell Transplant: Allogeneic Peripheral Blood Stem Cell Rescue. Day 0 Infusion of allogeneic peripheral blood stem cells. For the allogeneic matched-related donors peripheral blood stem cells will be harvested with GCSF mobilization and infused fresh to the recipients. Allogeneic donor stem cells may also be cryopreserved if they cannot be infused fresh.

B: Autologous Stem Cell Transplant

Autologous Stem Cell Transplant: Melphalan+Bortezomib followed by Autologous Rescue.

Group Type: OTHER

Bortezomib

Intervention Type: DRUG

AUTOLOGOUS ARM: Day -3 bortezomib (1.3 mg/m\^2) as an intravenous push over 3 to 5 seconds (follows Melphalan infusion). ALLOGENEIC ARM: Day -3 bortezomib (1.3 mg/m\^2) as an intravenous push over 3 to 5 seconds (follows fludarabine and melphalan infusion).

Melphalan

Intervention Type: DRUG

AUTOLOGOUS ARM: Day -4 and Day -3 Melphalan 100 mg/m\^2/day IV over 30 minutes. ALLOGENEIC ARM: Day -4, Day -3 Melphalan 70 mg/m\^2/day IV over 30 minutes.

Autologous Stem Cell Transplant

Intervention Type: PROCEDURE

Autologous Stem Cell Transplant: Autologous Peripheral Blood Stem Cell Rescue. Stem cell mobilization with granulocyte colony-stimulating factor (GCSF) at a dose of 10 μg/kg/day as per institutional standards. CD34+ peripheral blood stem cells will be collected following the administration of G-CSF as per institutional standards. Day 0 Infusion of autologous stem cells.

BE: Group B Expansion

Group B Expansion on Bortezomib Maintenance: Autologous Only.

Group Type: OTHER

Bortezomib

Intervention Type: DRUG

AUTOLOGOUS ARM: Day -3 bortezomib (1.3 mg/m\^2) as an intravenous push over 3 to 5 seconds (follows Melphalan infusion). ALLOGENEIC ARM: Day -3 bortezomib (1.3 mg/m\^2) as an intravenous push over 3 to 5 seconds (follows fludarabine and melphalan infusion).

Melphalan

Intervention Type: DRUG

AUTOLOGOUS ARM: Day -4 and Day -3 Melphalan 100 mg/m\^2/day IV over 30 minutes. ALLOGENEIC ARM: Day -4, Day -3 Melphalan 70 mg/m\^2/day IV over 30 minutes.

Autologous Stem Cell Transplant

Intervention Type: PROCEDURE

Autologous Stem Cell Transplant: Autologous Peripheral Blood Stem Cell Rescue. Stem cell mobilization with granulocyte colony-stimulating factor (GCSF) at a dose of 10 μg/kg/day as per institutional standards. CD34+ peripheral blood stem cells will be collected following the administration of G-CSF as per institutional standards. Day 0 Infusion of autologous stem cells.

Interventions

Bortezomib

AUTOLOGOUS ARM: Day -3 bortezomib (1.3 mg/m\^2) as an intravenous push over 3 to 5 seconds (follows Melphalan infusion). ALLOGENEIC ARM: Day -3 bortezomib (1.3 mg/m\^2) as an intravenous push over 3 to 5 seconds (follows fludarabine and melphalan infusion).

Intervention Type: DRUG

Melphalan

AUTOLOGOUS ARM: Day -4 and Day -3 Melphalan 100 mg/m\^2/day IV over 30 minutes. ALLOGENEIC ARM: Day -4, Day -3 Melphalan 70 mg/m\^2/day IV over 30 minutes.

Intervention Type: DRUG

Autologous Stem Cell Transplant

Autologous Stem Cell Transplant: Autologous Peripheral Blood Stem Cell Rescue. Stem cell mobilization with granulocyte colony-stimulating factor (GCSF) at a dose of 10 μg/kg/day as per institutional standards. CD34+ peripheral blood stem cells will be collected following the administration of G-CSF as per institutional standards. Day 0 Infusion of autologous stem cells.

Intervention Type: PROCEDURE

Fludarabine

Days -6,-5,-4,-3 Fludarabine 30 mg/m\^2/day IV

Intervention Type: DRUG

Allogeneic Stem Cell Transplant

Allogeneic Stem Cell Transplant: Allogeneic Peripheral Blood Stem Cell Rescue. Day 0 Infusion of allogeneic peripheral blood stem cells. For the allogeneic matched-related donors peripheral blood stem cells will be harvested with GCSF mobilization and infused fresh to the recipients. Allogeneic donor stem cells may also be cryopreserved if they cannot be infused fresh.

Intervention Type: PROCEDURE

Other Intervention Names

Velcade; Alkeran(R); Fludara(R)

Eligibility Criteria

Inclusion Criteria

Multiple Myeloma Criteria(International Uniform Response Criteria for Multiple Myeloma)

• Patients with responsive disease after any line of induction therapy
• A complete response
• A very good partial response
• A partial response
• Patients greater than or equal to 18 years of age are eligible. There is upper age limit of 60 years for allogeneic transplants.
• Patients must have a histologically confirmed diagnosis.
• All patients should have a life expectancy of at least 12 weeks.
• Patients must have undergone a complete psychosocial evaluation and have been considered capable of compliance.
• Meet the following criteria for allogeneic hematopoietic cell transplant:
• Must have an identified donor match defined as: HLA-A, HLA-B, HLA- C, DRB1 8/8 allele matched sibling, family member, or unrelated donor. [7/8 would go on separate mismatched trials] and be < 60 years of age.
• Calculated hematopoietic cell transplantation-specific comorbidity index (HCT-CI) <3

Exclusion Criteria

• Patients who do not achieve at least a partial response (PR) by the criteria mentioned above with induction therapy.
• Patient has a platelet count of <30 x 10^9/L within 14 days before enrollment.
• Patient has >/= Grade 2 peripheral neuropathy within 30 days before enrollment.
• Patient has an absolute neutrophil count of <1.0 x 10^9/L within 30 days before enrollment.
• Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant in order for the subject to be considered eligible. Left ventricular ejection fraction (LVEF) by multiple gated acquisition (MUGA) scan < 40%.
• Patient has hypersensitivity to bortezomib, boron or mannitol.
• Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
• Patient has received other investigational drugs with 30 days before enrollment
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Patients with a diffusing capacity of lung for carbon monoxide (DLCO) less than 50% (adjusted) of normal or with symptomatic obstructive or restrictive lung disease are ineligible.
• Patients with a total bilirubin greater than 2.0 mg/dL excluding Gilbert's syndrome and serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) greater than two and a half times normal (unless due to primary malignancy), or a history of severe hepatic dysfunction are ineligible.
• Calculated creatinine clearance </= 30 ml/min within 30 days before enrollment
• Patients with active infections are ineligible.
• Patients who are HIV positive are ineligible.
• Patients with active leptomeningeal involvement are ineligible. Patients with a history of previous cerebrospinal fluid (CSF) tumor involvement without symptoms or signs are eligible provided the CSF is now free of disease on lumbar puncture, and MRI of the brain shows no tumor involvement. Patients with severe symptomatic central nervous system (CNS) disease of any etiology are ineligible.
• Patients with uncontrolled insulin-dependent diabetes mellitus defined as a random glucose level of > 400 in the 30 days prior to initiation of study therapy; or uncompensated major thyroid or adrenal dysfunction are ineligible.
• Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of >/= 2(Karnofsky < 50%) are ineligible.
• Patients with an ECOG performance status of 2 to 3(Karnofsky 30-50%), secondary to bone pain, may be enrolled.
• Patients with an ECOG performance status of 2 to 3(Karnofsky 30-50%), secondary to a potentially reversible disease-related problem, may be enrolled.
• Patients with any previous malignancy other than non-melanoma skin cancer are ineligible, unless the patient is without evidence of disease >/= 5 years after the treatment for the cancer was completed.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Melissa Alsina, MD

Role: PRINCIPAL_INVESTIGATOR

H. Lee Moffitt Cancer Center and Research Institute

Jose Ochoa-Bayona, MD

Role: PRINCIPAL_INVESTIGATOR

H. Lee Moffitt Cancer Center and Research Institute

Locations

H. Lee Moffitt Cancer Center

Tampa, Florida, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.moffitt.org

H. Lee Moffitt Cancer Center \& Research Institute website

Other Identifiers

XO5271

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

MCC-15697

Identifier Type: -

Identifier Source: org_study_id