Phase II Study of V-BEAM Conditioning Regimen Prior to Second Autologous Stem Cell Transplantation

NCT01653418 | Terminated Phase 2 Results

• 1 other identifier: 201208046
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

BEAM regimen (BCNU, etoposide, cytarabine, and melphalan) is the most commonly used conditioning regimen for relapsed/refractory lymphoma patients needing autologous stem cell transplantation. Since these components are all effective in myeloma and bortezomib has shown promising results in the transplant setting, here the investigators propose a phase II study to investigate the combination of bortezomib and BEAM as a new conditioning regimen for patients who relapse or progress after the first autologous transplantation and for whom a second autologous transplant is considered.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate (Complete Response + Stringent Complete Response)

  Defined by the International Myeloma Working Group (IMWG) criteria

  Day +100

Secondary Outcomes (8)

• Number of Participants With Progression-free Survival (PFS)

  Median follow-up of 6 months (range: 6.0-12.0 months)

• Overall Response Rate (ORR)

  3 months following Day +100 visit

• Very Good Partial Response Rate (VGPR+nCR+sCR+CR)

  Day +100

• Toxicity of V-BEAM

  30 days after end of treatment / Day +100

• Time to Neutrophil Engraftment After V-BEAM.

  Day +100

Study Arms (1)

V-BEAM + Stem Cell Infusion

EXPERIMENTAL

Bortezomib IV or SC (1.3mg/m2) on Days -6, -3, +1 and +4 Carmustine IV (300mg/m2) on Day -7 Etoposide IV twice daily (100 mg/m2) on Days -6, -5, -4, and -3 Cytarabine IV twice daily (100 mg/m2) on Days -6, -5, -4, and -3 Melphalan IV (140 mg/m2) on Day-2 Stem cell infusion on Day 0

Drug: Bortezomib; Drug: Carmustine; Drug: Etoposide; Drug: Cytarabine; Drug: Melphalan; Procedure: Stem cell infusion

Interventions

Bortezomib DRUG

Also known as: Velcade

V-BEAM + Stem Cell Infusion

Carmustine DRUG

Also known as: BCNU, BiCNU®

V-BEAM + Stem Cell Infusion

Etoposide DRUG

Also known as: Vepesid, VP-16

V-BEAM + Stem Cell Infusion

Cytarabine DRUG

Also known as: Ara-C, Cytosar-U, 1-β-Arabinofuranosylcytosine, Arabinosylcytosine, Cytosine arabinoside

V-BEAM + Stem Cell Infusion

Melphalan DRUG

Also known as: Alkeran®, L-PAM

V-BEAM + Stem Cell Infusion

Stem cell infusion PROCEDURE

V-BEAM + Stem Cell Infusion

Eligibility Criteria

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

You may qualify if:

• Patient must have a histologically confirmed diagnosis of multiple myeloma.
• Patient must have received a prior autologous stem cell transplantation with melphalan conditioning for multiple myeloma with subsequent disease progression and repeat autologous stem cell transplantation is deemed appropriate by the treating physicians.
• Patient must receive induction chemotherapy including 2 to 4 cycles of anti-myeloma therapy including bortezomib, with or without immune modulating agents and/or corticosteroids, Completion of induction therapy will occur within 30 days of first study drug dose.
• Patient must have ≥ 2x106/kg CD34+ autologous stem cells available for transplantation.
• Patient must be ≥ 18 years of age.
• Patient must have life expectancy of greater than 6 months.
• Patient must have an ECOG performance status ≤ 2 or Karnofsky performance status ≥ 60% (see Appendices A and B)
• Patient must have normal bone marrow and organ function as defined below within 14 days prior to first study drug dose (conditioning regimen):
• Absolute neutrophil count ≥500/mm3
• Platelets ≥ 50,000/mm3
• Hemoglobin ≥ 8 g/dl
• Total bilirubin ≤ 1.5 x IULN
• AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
• Creatinine clearance (Appendix C) ≥30 mL/min/1.73m2
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry through Day +100 visit. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.

You may not qualify if:

• Patient must not be refractory to induction therapy. Refractory is defined as disease progression while on therapy or within 30 days following completion of therapy.
• Patient must not have had disease progression requiring active treatment within 12 months of previous autologous stem cell transplant. Maintenance therapy is not considered active treatment.
• Patient must not have peripheral neuropathy ≥ grade 3 based on NCI CTCAE v 4.0 (Appendix D).
• Patient must not be receiving renal replacement therapy, hemodialysis, or peritoneal dialysis.
• Patient must not have another concurrent malignancy requiring treatment.
• Patient must not be receiving any other investigational agents within 14 days prior to the first dose of study drug.
• Patient must not have known brain metastases. Patients with known brain metastases must be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Patient must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to bortezomib, carmustine, etoposide, cytarabine, and melphalan, or other agents used in the study.
• Patient must not have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patient must not be pregnant and/or breastfeeding.
• Both men and women and members of all races and ethnic groups are eligible for this trial.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63122, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; Carmustine; Etoposide; Cytarabine; Melphalan

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

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Limitations and Caveats

2 early deaths caused a concern for safety and resulted in suspension of enrollment in May 2013. After a review of the data, the investigators determined that this regimen had unexpected toxicity \& the trial was closed to enrollment in June 2013.

Results Point of Contact

• Title: Ravi Vij, M.D.
• Organization: Washington University School of Medicine

rvij@dom.wustl.edu

314-454-8304

Study Officials

• Ravi Vij, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: July 23, 2012
• First Posted: July 31, 2012
• Study Start: September 1, 2012
• Primary Completion: August 1, 2013
• Study Completion: December 1, 2013
• Last Updated: October 15, 2014
• Results First Posted: October 15, 2014

Record last verified: 2014-10

Locations

US (1)