Post-Transplant Bortezomib and High Dose Cyclophosphamide as Graft-Versus-Host Disease (GVHD) Prophylaxis

NCT01860170 | Completed Phase 1 Results DMC

• 1 other identifier: 2013-083
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if Bortezomib, known commercially as Velcade is safe and tolerated at different dose levels (amounts) with high dose Cyclophosphamide to be used as graft versus host disease prevention after reduced-intensity allogeneic hematopoietic stem cell transplantation.

Conditions

Hematological Malignancy

Keywords

Blood and Marrow Transplant (BMT); MRD; MUD; GVHD

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity

  Grade 3 non-hematologic Common Toxicity Criteria toxicity directly related to bortezomib (such as peripheral neuropathy) or Grade 2 or \> hepatic bilirubin Common Toxicity Criteria Graft failure

  Assessed daily (while inpatient) through clinical and laboratory examination up to 90 days.

Secondary Outcomes (1)

• Engraftment

  Assessed daily by laboratory evaluation until engraftment or up to 90 days.

Other Outcomes (1)

• GVHD

  Assessed routinely by clinical and pathological evaluation. Acute GVHD will be assessed up to day 150 post-transplant. Chronic GVHD will be assess up to 2 years post-transplant.

Study Arms (3)

Cohort 1-Bortezomib (Velcade®)

ACTIVE COMPARATOR

Bortezomib (Velcade®) 0.7 mg/m2 rapid IV push on days 0 (at least 6 hours after transplant) and +3.

Drug: Cohort 1-Bortezomib (Velcade ®)

Cohort 2-Bortezomib (Velcade®)

ACTIVE COMPARATOR

Bortezomib (Velcade®) 1 mg/ m2 rapid IV push on days 0 (at least 6 hours after transplant) and +3.

Drug: Cohort 2-Bortezomib (Velcade ®)

Cohort 3-Bortezomib (Velcade®)

ACTIVE COMPARATOR

Bortezomib (Velcade®) 1.3 mg/m2 rapid IV push on days 0 (at least 6 hours after transplant) and +3.

Drug: Cohort 3-Bortezomib (Velcade ®)

Interventions

Cohort 1-Bortezomib (Velcade ®) DRUG

Conditioning Regimen: Fludarabine 30 mg/m2 on days -7, -6, -5, -4, -3 and -2; Busulfan 0.8 mg/kg, every 6 hours on days -3 and -2; Patients with matched unrelated donor also receive rATG (Thymoglobulin ®) 2 mg/kg on days -4, -3, -2 and -1. Cyclophosphamide 50 mg/kg, in 500 mL NS over 2 hours on days +3 and +4. Concomitant hydration with NS with 20 mEq/L at 250 mL/hr starting 4 hours before and continuing until 24 hours after the second dose is given. Furosemide on as needed basis to maintain fluid balance is also given. It is important to avoid administration of any immunosuppressive drugs include steroids after day 0. Bortezomib 0.7 mg/m2 rapid IV push on days 0 (at least 6 hours after transplant) and +3.

Also known as: Cyclophosphamide (Cytoxan ®), Bortezomib (Velcade ®)

Cohort 1-Bortezomib (Velcade®)

Cohort 2-Bortezomib (Velcade ®) DRUG

Conditioning Regimen: Fludarabine 30 mg/m2 on days -7, -6, -5, -4, -3 and -2; Busulfan 0.8 mg/kg, every 6 hours on days -3 and -2; Patients with matched unrelated donor also receive rATG (Thymoglobulin ®) 2 mg/kg on days -4, -3, -2 and -1. Cyclophosphamide 50 mg/kg, in 500 mL NS over 2 hours on days +3 and +4. Concomitant hydration with NS with 20 mEq/L at 250 mL/hr starting 4 hours before and continuing until 24 hours after the second dose is given. Furosemide on as needed basis to maintain fluid balance is also given. It is important to avoid administration of any immunosuppressive drugs include steroids after day 0. Bortezomib 1 mg/ m2 rapid IV push on days 0 (at least 6 hours after transplant) and +3.

Also known as: Cyclophosphamide (Cytoxan ®), Bortezomib (Velcade ®)

Cohort 2-Bortezomib (Velcade®)

Cohort 3-Bortezomib (Velcade ®) DRUG

Conditioning Regimen: Fludarabine 30 mg/m2 on days -7, -6, -5, -4, -3 and -2; Busulfan 0.8 mg/kg, every 6 hours on days -3 and -2; Patients with matched unrelated donor also receive rATG (Thymoglobulin ®) 2 mg/kg on days -4, -3, -2 and -1. Cyclophosphamide 50 mg/kg, in 500 mL NS over 2 hours on days +3 and +4. Concomitant hydration with NS with 20 mEq/L at 250 mL/hr starting 4 hours before and continuing until 24 hours after the second dose is given. Furosemide on as needed basis to maintain fluid balance is also given. It is important to avoid administration of any immunosuppressive drugs include steroids after day 0. Bortezomib 1.3 mg/m2 rapid IV push on days 0 (at least 6 hours after transplant) and +3.

Also known as: Cyclophosphamide (Cytoxan ®), Bortezomib (Velcade ®)

Cohort 3-Bortezomib (Velcade®)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• out of 8 matched related or unrelated donor
• Age \> 18 years
• Good performance status with a Karnofsky score \>/= to 70%
• No evidence of progressive bacterial, viral or fungal infection despite adequate treatment
• Creatinine clearance \> 40 mL/min/1.72m2
• Total bilirubin \< 1.5 and ALT and AST \< 2 times the upper limit of normal
• Cardiac ejection fraction \> 40%
• DLCO \> 50%
• Negative pregnancy test
• Negative HIV serology
• Able to provide informed consent
• Female subject is either postmenopausal for at least 1 year before the screening visit, is surgically sterilized or if they are of childbearing potential, agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of bortezomib, or agree to completely abstain from heterosexual intercourse.
• Male subjects, even if surgically sterilized (ie, status postvasectomy) must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse.

You may not qualify if:

• Age \<18 years
• Poor performance status (\<70%)
• Active infections
• Abnormal creatinine clearance \<40ml/min
• Elevated bilirubin \>1.5 and ALT and AST .2 times the upper limit of normal
• Poor ejection fraction \<40%
• DLCO \<50%
• Pregnant female.
• HIV positive
• Inability to provide informed consent
• Patient has \>/= Grade 2 peripheral neuropathy
• Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.
• Patient has hypersensitivity to bortezomib, boron, or mannitol.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.

Sponsors & Collaborators

• Corewell Health West: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Spectrum Health

Grand Rapids, Michigan, 49503, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

Bortezomib; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: A. Samer A;-Homsi
• Organization: Spectrum Health

a.samer.al-homsi@spectrumhealth.org

616-486-5933

Study Officials

• A. Samer Al-Homsi, MD

  Corewell Health West

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2013
• First Posted: May 22, 2013
• Study Start: April 1, 2012
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2018
• Last Updated: June 2, 2023
• Results First Posted: May 17, 2017

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)