Exploratory Trial to Estimate Proportion of Patients With Tumor Cell Contaminated Leukapheresis Products With and Without Bortezomib With In-vivo Purging - Multiple Myeloma (MM)

NCT ID: NCT02703779

Last Updated: 2021-06-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 101 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2020-04-08

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).

Conditions

Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Stem cell collection without in-vivo purging with Bortezomib

Standard of Care Stem cell collection without in-vivo purging with Bortezomib. Standard of Care drugs Granulocyte colony-stimulating factor (G-CSF) +/- Mozobil (the latter if needed).

NOTE: Multiparametric Flow Cytometry to be performed on samples for BOTH groups A and B

Group Type: ACTIVE_COMPARATOR

Granulocyte colony-stimulating factor (G-CSF)

Intervention Type: DRUG

Granulocyte colony-stimulating factor (G-CSF) will be given to all participants by injection under the skin 4 days and 1 day before stem cell collection, and then continued until the stem cell collection is completed.

Mozobil

Intervention Type: DRUG

Mozobil will be given to all participants by injection under the skin only if needed per Investigator.

Stem cell collection with in-vivo purging with Bortezomib

Bortezomib will be given subcutaneously (SQ) at 1.3 mg/m2 on day -11 and day -8 followed by Granulocyte colony-stimulating factor (G-CSF) given SQ on day -4 thru day -1 and continued until the collection is completed. Mozobil will be given if needed.

There must be at least 72 hours between each dose of bortezomib. NOTE: Multiparametric Flow Cytometry to be performed on samples for BOTH groups A and B

Group Type: EXPERIMENTAL

Bortezomib

Intervention Type: DRUG

Bortezomib will be given to Group B participants by injection under the skin 11 days and 8 days before stem cell collection.

Granulocyte colony-stimulating factor (G-CSF)

Intervention Type: DRUG

Granulocyte colony-stimulating factor (G-CSF) will be given to all participants by injection under the skin 4 days and 1 day before stem cell collection, and then continued until the stem cell collection is completed.

Mozobil

Intervention Type: DRUG

Mozobil will be given to all participants by injection under the skin only if needed per Investigator.

Interventions

Bortezomib

Bortezomib will be given to Group B participants by injection under the skin 11 days and 8 days before stem cell collection.

Intervention Type: DRUG

Granulocyte colony-stimulating factor (G-CSF)

Granulocyte colony-stimulating factor (G-CSF) will be given to all participants by injection under the skin 4 days and 1 day before stem cell collection, and then continued until the stem cell collection is completed.

Intervention Type: DRUG

Mozobil

Mozobil will be given to all participants by injection under the skin only if needed per Investigator.

Intervention Type: DRUG

Other Intervention Names

VELCADE; NEUPOGEN; filgrastim; filgrastim-sndz; Zarxio; plerixafor

Eligibility Criteria

Inclusion Criteria

• 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

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Siddhartha Ganguly

OTHER

Sponsor Role: lead

Responsible Party

Siddhartha Ganguly

Medical Doctor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Siddhartha Ganguly, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Kansas - Cancer Center

Locations

The University of Kansas Medical Center

Westwood, Kansas, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 18268286 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

2015-IIT-BMT-MM-AutoSCT

Identifier Type: -

Identifier Source: org_study_id