Clinical trial NCT01653418: Phase II Study of V-BEAM Conditioning Regimen Prior to Second Autologous Stem Cell Transplantation
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Multiple Myeloma
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2012-07-31
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Complete Response Rate (Complete Response + Stringent Complete Response)
timeFrame: Day +100
Secondary outcomes:
measure: Number of Participants With Progression-free Survival (PFS)
timeFrame: Median follow-up of 6 months (range: 6.0-12.0 months)
measure: Overall Response Rate (ORR)
timeFrame: 3 months following Day +100 visit
measure: Very Good Partial Response Rate (VGPR+nCR+sCR+CR)
timeFrame: Day +100
measure: Toxicity of V-BEAM
timeFrame: 30 days after end of treatment / Day +100
measure: Time to Neutrophil Engraftment After V-BEAM.
timeFrame: Day +100
measure: Number of Participants With Overall Survival (OS)
timeFrame: Median follow-up of 6 months (range: 6-12 months)
measure: Treatment Related Mortality (TRM) of V-BEAM
timeFrame: Day +100
measure: Time to Platelet Engraftment After V-BEAM.
timeFrame: Day +100
Other outcomes:
Locations:
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Ravi Vij, M.D.
role: PRINCIPAL_INVESTIGATOR
References: