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

This study has been terminated.
(Due to the high rate of morbidity and mortality)
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01653418
First received: July 23, 2012
Last updated: October 8, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: Bortezomib
Drug: Carmustine
Drug: Etoposide
Drug: Cytarabine
Drug: Melphalan
Procedure: Stem cell infusion
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of V-BEAM (Bortezomib, Carmustine, Etoposide, Cytarabine, and Melphalan) as Conditioning Regimen Prior to Second Autologous Stem Cell Transplantation for Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Complete Response Rate (Complete Response + Stringent Complete Response) [ Time Frame: Day +100 ] [ Designated as safety issue: No ]
    Defined by the International Myeloma Working Group (IMWG) criteria


Secondary Outcome Measures:
  • Number of Participants With Progression-free Survival (PFS) [ Time Frame: Median follow-up of 6 months (range: 6.0-12.0 months) ] [ Designated as safety issue: No ]

    PFS is defined as the duration from transplant to time of first progression, death, relapse after CR, or the date the patient was last known to be in remission.

    Response will be assessed per the International Myeloma Working Group (IMWG) Response Criteria.


  • Overall Response Rate (ORR) [ Time Frame: 3 months following Day +100 visit ] [ Designated as safety issue: No ]

    ORR includes Partial Response (PR) + Very Good Partial Response (VGPR) + Complete Response (CR)

    Response will be assessed per the International Myeloma Working Group (IMWG) Response Criteria.


  • Very Good Partial Response Rate (VGPR+nCR+sCR+CR) [ Time Frame: Day +100 ] [ Designated as safety issue: No ]
    Response will be assessed per the International Myeloma Working Group (IMWG) Response Criteria.

  • Toxicity of V-BEAM [ Time Frame: 30 days after end of treatment / Day +100 ] [ Designated as safety issue: Yes ]

    Graded per the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

    Patients are evaluated from first receiving study treatment until a 30-day follow-up after the conclusion of treatment for adverse events not resulting in death. Adverse events resulting in death will be evaluated through Day +100.

    This outcomes measures the common toxicities observed. Please refer to the Serious Adverse Event and Other Adverse Event sections of the results for further details.


  • Time to Neutrophil Engraftment After V-BEAM. [ Time Frame: Day +100 ] [ Designated as safety issue: Yes ]
    Time to neutrophil engraftment is defined as duration between Day 0 to the first day of ANC > 0.5x109/L post transplant when it is sustained for more than three consecutive days.

  • Number of Participants With Overall Survival (OS) [ Time Frame: Median follow-up of 6 months (range: 6-12 months) ] [ Designated as safety issue: No ]
    OS is defined as the duration from the time of transplant to death or last follow-up.

  • Treatment Related Mortality (TRM) of V-BEAM [ Time Frame: Day +100 ] [ Designated as safety issue: Yes ]
  • Time to Platelet Engraftment After V-BEAM. [ Time Frame: Day +100 ] [ Designated as safety issue: Yes ]
    Time to platelet engraftment is defined as the duration between Day 0 to the first day of platelet count sustained at > 20x109/L without transfusion. The median time to neutrophil and platelet engraftment will be reported.


Enrollment: 10
Study Start Date: September 2012
Study Completion Date: December 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: V-BEAM + Stem Cell Infusion
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
Other Name: Velcade
Drug: Carmustine
Other Name: BCNU, BiCNU®
Drug: Etoposide
Other Name: Vepesid, VP-16
Drug: Cytarabine
Other Name: Ara-C, Cytosar-U, 1-β-Arabinofuranosylcytosine, Arabinosylcytosine, Cytosine arabinoside
Drug: Melphalan
Other Name: Alkeran®, L-PAM
Procedure: Stem cell infusion

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • Patient must be able to understand and willing to sign an IRB approved written informed consent document.

Exclusion Criteria:

  • 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.

Inclusion of Women and Minorities

-Both men and women and members of all races and ethnic groups are eligible for this trial.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01653418

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63122
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Ravi Vij, M.D. Washington University School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01653418     History of Changes
Other Study ID Numbers: 201208046
Study First Received: July 23, 2012
Results First Received: September 26, 2014
Last Updated: October 8, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Bortezomib
Carmustine
Cytarabine
Etoposide
Etoposide phosphate
Melphalan
Alkylating Agents
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors

ClinicalTrials.gov processed this record on October 29, 2014