Clinical trial NCT02703779: Exploratory Trial to Estimate Proportion of Patients With Tumor Cell Contaminated Leukapheresis Products With and Without Bortezomib With In-vivo Purging - Multiple Myeloma (MM)
Official title: An Exploratory Trial to Estimate the Proportion of Patients With Tumor Cell Contaminated, Flow Positive Leukapheresis Products Collected With and Without Bortezomib as In-vivo Purging Prior to Autologous Stem Cell Harvest for Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Bortezomib
Autologous
Stem Cell
Purging
In-vivo purging
Ex-vivo purging
Leukapheresis
Contaminated
Stem Cell Harvest
Stem Cell Transplant
Transplantation
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
First posted: 2016-03-09
Enrollment: 101
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Explore stem cell collection with or without bortezomib with in-vivo purging in multiple myeloma.

Detailed description: High dose chemotherapy with autologous stem cell transplant has resulted in improved overall survival and is currently considered an effective first line therapy applicable to the majority of patients with multiple myeloma. However disease relapse is inevitable and remains the primary cause of mortality in this cohort.

The purpose of this study is to estimate the proportion of subjects with plasma cell contamination of harvested stem cell product in standard and treatment arms. The study will explore whether or not in-vivo purging of malignant tumor plasma cells will improve progression free survival (PFS) for patients.

The study will consist of two groups:

Group A: Standard of Care (SOC) stem cell collection without in-vivo purging with bortezomib. Granulocyte colony-stimulating factor (G-CSF) and Mozobil used if needed.

Group B: Bortezomib 1.3mg/m\^2 will be given subcutaneously (SQ) on days -11 and -8 followed by Granulocyte colony-stimulating factor (G-CSF) on days -4 through -1 prior to stem cell harvest (day 0).

Eligibility criteria: Inclusion Criteria:

* Subjects must meet all of the inclusion criteria to participate in this study.
* Ability to understand, and the willingness to sign a written Informed Consent Form
* Diagnosis of multiple myeloma undergoing planned autologous stem cell transplantation
* Age ≥ 18 years
* Karnofsky Performance Status (KPS) 70 or above, Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2
* Adequate organ and marrow function as defined below:

  * leukocytes ≥ 3,000/micro Liter (mcL)
  * absolute neutrophil count ≥ 1,500/mcL
  * platelets ≥ 100,000/mcL
  * total bilirubin within normal institutional limits NOTE: For this study, subjects with bilirubin levels \> 1.5 Upper Limit of Normal (ULN) are excluded from enrollment in this study.
  * Aspartate Aminotransferase (AST) ( Serum Glutamic Oxaloacetic Transaminase \[SGOT\]) ≤ 2.5 X institutional upper limit of normal
  * Alanine Aminotransferase (ALT) (Serum Pyruvic Glutamic Transaminase \[SPGT\]) ≤ 2.5 X institutional upper limit of normal
  * creatinine within normal institutional limits
* Women of child-bearing potential and men with partners of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 30 days following completion of therapy. Should a woman or partner become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician and the investigator immediately.
* A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

  * Has not undergone a hysterectomy or bilateral oophorectomy; or
  * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)

Exclusion Criteria:

* Subjects meeting any of the exclusion criteria at baseline will be excluded from study participation.
* Current or anticipated use of other investigational agents. NOTE the following clarification for this study: Prohibited Concurrent Therapy:

Participation in clinical trials with other investigational agents that are not included in this trial, within 14 days of the start of this trial until 2 weeks after participant has received the last dose of bortezomib for mobilization.

* Hypersensitivity to bortezomib, boron or mannitol or Granulocyte colony-stimulating factor (G-CSF)
* Subject has received \> 6 months of lenalidomide (Revlimid®) therapy prior to stem cell collection
* Subject has known brain metastases. Presence of brain metastases should be excluded from this clinical trial because of poor prognosis and because patients often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
* Grade 3 or higher peripheral neuropathy
* Bilirubin levels \> 1.5 ULN
* Uncontrolled inter-current illness including, but not limited to

  * ongoing or active infection
  * symptomatic congestive heart failure
  * unstable angina pectoris
  * cardiac arrhythmia
  * psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant or nursing: There is a potential for congenital abnormalities and for this regimen to harm nursing infants.

Primary outcomes:
measure: Multiparametric Flow Cytometry - Minimum Residual Disease
timeFrame: Day 0 for all subjects (Day 0 is the day of stem cell collection)
Secondary outcomes:
measure: Multiparametric Flow Cytometry - Cluster of Differentiation 34 (CD34)Assessment
timeFrame: Within the first 30 days after stem cell collection
measure: Cluster of Differentiation 34 (CD34) Enumeration
timeFrame: Within the first 30 days after stem cell collection
Other outcomes:
Locations:
city: Westwood
country: United States
facility: The University of Kansas Medical Center
state: Kansas
Study officials:
affiliation: The University of Kansas - Cancer Center
name: Siddhartha Ganguly, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rawstron AC, Orfao A, Beksac M, Bezdickova L, Brooimans RA, Bumbea H, Dalva K, Fuhler G, Gratama J, Hose D, Kovarova L, Lioznov M, Mateo G, Morilla R, Mylin AK, Omede P, Pellat-Deceunynck C, Perez Andres M, Petrucci M, Ruggeri M, Rymkiewicz G, Schmitz A, Schreder M, Seynaeve C, Spacek M, de Tute RM, Van Valckenborgh E, Weston-Bell N, Owen RG, San Miguel JF, Sonneveld P, Johnsen HE; European Myeloma Network. Report of the European Myeloma Network on multiparametric flow cytometry in multiple myeloma and related disorders. Haematologica. 2008 Mar;93(3):431-8. doi: 10.3324/haematol.11080. Epub 2008 Feb 11.