Bortezomib Followed by High-Dose Melphalan and Bortezomib as Conditioning Regimen for Tandem Stem Cell Transplants

NCT00307086 | Completed Phase 2 Results DMC

• 2 other identifiers: MCC-14184X05174
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objectives of this study are to:

• To determine the maximum tolerated dose (MTD) of bortezomib in combination with high-dose melphalan as a conditioning regimen.
• To determine the safety, tolerability, and response rates of bortezomib given in combination with high-dose melphalan, as a conditioning regimen, for tandem transplants in patients with primary refractory multiple myeloma or plasma cell leukemia. The secondary objectives of this study are to:
• To determine gene expression profiles (pharmacogenomics) and perform RTPCR for Fanconi anemia pathway genes, prior to and after treatment with bortezomib, in patients with primary refractory multiple myeloma and plasma cell leukemia and correlate profiles with responses to treatment.
• To determine the time to disease progression and overall survival in patients with primary refractory multiple myeloma and plasma cell leukemia treated with bortezomib followed by tandem autologous transplantation
• To determine the response rates of 2 cycles of bortezomib in patients with primary refractory multiple myeloma or plasma cell leukemia

Conditions

Multiple Myeloma; Plasma Cell Leukemia

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  Median overall survival after first peripheral blood stem cell transplant (PBSCT).

  40 months post transplant

Study Arms (1)

Autologous PBSCT

OTHER

bortezomib in combination with high-dose melphalan as a conditioning regimen for autologous peripheral blood stem cell transplant (PBSCT)

Drug: Bortezomib; Drug: Melphalan; Procedure: PBSCT

Interventions

Bortezomib DRUG

the maximum tolerated dose (MTD) of bortezomib in combination with high-dose melphalan as a conditioning regimen for autologous stem cell transplant

Also known as: Velcade

Autologous PBSCT

Melphalan DRUG

Day -4 melphalan 100 mg/m2 intravenously over 30 minutes, Day -3 melphalan 100 mg/m2 intravenously over 30 minutes

Also known as: Alkeran(R)

Autologous PBSCT

PBSCT PROCEDURE

PBSCT #1 Day 0 PBSCT #2 Day 0 (approx 90 days =/- 15 days after PBSCT #1)

Also known as: peripheral blood stem cell transplant (PBSCT)

Autologous PBSCT

Eligibility Criteria

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

You may qualify if:

• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• Female is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
• Male agrees to use an acceptable method for contraception for the duration of the study.
• Multiple Myeloma Criteria:
• Patients with primary refractory disease (those failing to achieve at least a partial response, as defined by the Bladé multiple myeloma response criteria, after first-line (induction) therapy). A partial response will be defined as the following: ≥50% reduction in the level of the serum monoclonal paraprotein, maintained for a minimum of 6 weeks, Reduction in 24-hour urinary light chain excretion either by ≥ 90% or to \< 200 mg, maintained for a minimum of 6 weeks. For patients with non-secretory myeloma only, ≥ 50% reduction in plasma cells in a bone marrow aspirate and biopsy, maintained for a minimum of 6 weeks, ≥ 50% reduction in the size of soft tissue plasmacytomas (by radiography or physical examination). No increase in the size or number of lytic bone lesions (development of a compression fracture does not exclude response).
• Patients with plasma cell leukemia, either newly diagnosed or previously treated.
• Patients greater than or equal to 18 years of age are eligible.
• Patients must have a histologically confirmed diagnosis by a pathologic review at the H. Lee Moffitt Cancer Center and Research Institute.
• Patients must have undergone a complete psychosocial evaluation and have been considered capable of compliance.

You may not qualify if:

• Patient has a platelet count of \<30× 10\^9/L within 14 days before enrollment.
• Patient has an absolute neutrophil count of \<1.0 × 10\^9/L within 14 days before enrollment.
• Patient has a serum creatinine of greater than 2.0 mg/dL OR a creatinine clearance of less than 40 ml/minute within 14 days before enrollment. Creatinine clearance can be measured or calculated.
• Has \>Grade 2 peripheral neuropathy within 14 days before enrollment.
• Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association (NYHA) Class III or IV heart failure (see section 8.4), 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.
• Patient has hypersensitivity to bortezomib, boron or mannitol.
• Female is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for postmenopausal or surgically sterilized women.
• Patient has received other investigational drugs with 14 days before enrollment
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Patients with a DLCO less than 50% (adjusted) of normal or with symptomatic obstructive or restrictive lung disease are ineligible.
• Patients with renal dysfunction secondary to multiple myeloma may be enrolled at the discretion of the principal investigator. However, patients on hemodialysis or peritoneal dialysis are ineligible.
• Patients with a total bilirubin greater than 2.0 mg/dL and SGOT or SGPT greater than two and a half times normal (unless due to primary malignancy), or a history of severe hepatic dysfunction are ineligible.
• 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 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 & Research Institute

Tampa, Florida, 33612, United States

Location

Related Links

• H Lee Moffitt Cancer Center \& Research Institute website

MeSH Terms

Conditions

Multiple Myeloma; Leukemia, Plasma Cell

Interventions

Bortezomib; Melphalan; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; 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; Leukemia

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; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Limitations and Caveats

per protocol subjects are followed for 2 years post transplant; however, subjects are followed on our long-term follow-up protocol(MCC12567/IRB6101) to assess overall and disease free survival. additional data available at time manuscript was written

Results Point of Contact

• Title: Mellisa Alsina, MD
• Organization: H. Lee Moffitt Cancer Center

Melissa.Alsina@moffitt.org

813-745-6886

Study Officials

• Melissa Alsina, MD

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

• Todd Alekshun, MD

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2006
• First Posted: March 27, 2006
• Study Start: June 1, 2005
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: March 6, 2017
• Results First Posted: October 24, 2013

Record last verified: 2013-08

Locations

US (1)