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

Multiple Myeloma Clinical Trial

— V-BEAM  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01653418
• Other study ID #: 201208046
• Status: Terminated
• Phase: Phase 2
• First received: July 23, 2012
• Last updated: October 8, 2014
• Start date: September 2012
• Est. completion date: December 2013

Study information

• Verified date: October 2014
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: December 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Bortezomib

• Carmustine

• Etoposide

• Cytarabine

• Melphalan

Procedure:
• Stem cell infusion

Locations

Country	Name	City	State
United States	Washington University School of Medicine	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Response Rate (Complete Response + Stringent Complete Response)	Defined by the International Myeloma Working Group (IMWG) criteria	Day +100	No
Secondary	Number of Participants With Progression-free Survival (PFS)	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.	Median follow-up of 6 months (range: 6.0-12.0 months)	No
Secondary	Overall Response Rate (ORR)	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.	3 months following Day +100 visit	No
Secondary	Very Good Partial Response Rate (VGPR+nCR+sCR+CR)	Response will be assessed per the International Myeloma Working Group (IMWG) Response Criteria.	Day +100	No
Secondary	Toxicity of V-BEAM	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.	30 days after end of treatment / Day +100	Yes
Secondary	Time to Neutrophil Engraftment After V-BEAM.	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.	Day +100	Yes
Secondary	Number of Participants With Overall Survival (OS)	OS is defined as the duration from the time of transplant to death or last follow-up.	Median follow-up of 6 months (range: 6-12 months)	No
Secondary	Treatment Related Mortality (TRM) of V-BEAM		Day +100	Yes
Secondary	Time to Platelet Engraftment After V-BEAM.	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.	Day +100	Yes

External Links

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