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

NCT00948922 | Completed Phase 2 Results DMC

• 2 other identifiers: MCC-15697XO5271
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Myeloma

Keywords

multiple myeloma; myeloma; myeloma proteins; autologous; allogeneic; G-CSR; granulocyte colony-stimulating factor; stem cell transplant; stem cell; stem cell mobilization

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  PFS: Number of participants, per treatment arm with progression free survival at time of analysis. Survival time will be measured from the date of transplant to the date of progression, death or the last follow-up, whichever comes first. Progressive Disease (PD): Increase of ≥ 25% from lowest response value in any one or more of the following: Serum M-component and/or; Urine M-component and/or; Only in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be \> 10 mg/dL; Bone marrow plasma cell percentage; absolute percentage ≥ 10%; Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia that can be attributed solely to the plasma cell proliferative disorder.

  End of 2 year, post transplant follow-up

Secondary Outcomes (2)

• Overall Survival (OS) Rate

  End of 2 year, post transplant follow-up

• Molecular Complete Response (CR) Rates in Patients With Multiple Myeloma

  End of 2 year, post transplant follow-up

Other Outcomes (1)

• Percentage of Participants With Acute or Chronic Graft-versus-host Disease (GVHD) Following Transplant

  End of 2 year, post transplant follow-up

Study Arms (3)

A: Allogeneic Stem Cell Transplant

OTHER

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

Drug: Bortezomib; Drug: Melphalan; Drug: Fludarabine; Procedure: Allogeneic Stem Cell Transplant

B: Autologous Stem Cell Transplant

OTHER

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

Drug: Bortezomib; Drug: Melphalan; Procedure: Autologous Stem Cell Transplant

BE: Group B Expansion

OTHER

Group B Expansion on Bortezomib Maintenance: Autologous Only.

Drug: Bortezomib; Drug: Melphalan; Procedure: Autologous Stem Cell Transplant

Interventions

Bortezomib 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).

Also known as: Velcade

A: Allogeneic Stem Cell Transplant; B: Autologous Stem Cell Transplant; BE: Group B Expansion

Melphalan 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.

Also known as: Alkeran(R)

A: Allogeneic Stem Cell Transplant; B: Autologous Stem Cell Transplant; BE: Group B Expansion

Autologous Stem Cell Transplant 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.

B: Autologous Stem Cell Transplant; BE: Group B Expansion

Fludarabine DRUG

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

Also known as: Fludara(R)

A: Allogeneic Stem Cell Transplant

Allogeneic Stem Cell Transplant 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.

A: Allogeneic Stem Cell Transplant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Related Links

• H. Lee Moffitt Cancer Center \& Research Institute website

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Bortezomib; Melphalan; fludarabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Limitations and Caveats

SAEs not recorded for participants off study, though they were followed for survival.

Results Point of Contact

• Title: Dr. Melissa Alsina
• Organization: H. Lee Moffitt Cancer Center and Research Institute

melissa.alsina@moffitt.org

813-745-7202

Study Officials

• Melissa Alsina, MD

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

• Jose Ochoa-Bayona, MD

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2009
• First Posted: July 29, 2009
• Study Start: June 18, 2009
• Primary Completion: April 20, 2017
• Study Completion: May 14, 2019
• Last Updated: September 18, 2019
• Results First Posted: October 12, 2018

Record last verified: 2019-06

Locations

US (1)