Overview

This trial is active, not recruiting.

Condition hematological malignancy
Treatments cohort 1-bortezomib (velcade ®), cohort 2-bortezomib (velcade ®), cohort 3-bortezomib (velcade ®)
Phase phase 1/phase 2
Sponsor Spectrum Health Hospitals
Collaborator Millennium Pharmaceuticals, Inc.
Start date April 2012
End date March 2016
Trial size 28 participants
Trial identifier NCT01860170, 2013-083

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety study
Intervention model parallel assignment
Masking open label
Primary purpose prevention
Arm
(Active Comparator)
Bortezomib (Velcade®) 0.7 mg/m2 rapid IV push on days 0 (at least 6 hours after transplant) and +3.
cohort 1-bortezomib (velcade ®) Cyclophosphamide (Cytoxan ®)
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.
(Active Comparator)
Bortezomib (Velcade®) 1 mg/ m2 rapid IV push on days 0 (at least 6 hours after transplant) and +3.
cohort 2-bortezomib (velcade ®) Cyclophosphamide (Cytoxan ®)
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.
(Active Comparator)
Bortezomib (Velcade®) 1.3 mg/m2 rapid IV push on days 0 (at least 6 hours after transplant) and +3.
cohort 3-bortezomib (velcade ®) Cyclophosphamide (Cytoxan ®)
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.

Primary Outcomes

Measure
Dose Limiting Toxicity
time frame: Assessed daily (while inpatient) through clinical and laboratory examination up to 90 days.

Secondary Outcomes

Measure
Engraftment
time frame: Assessed daily by laboratory evaluation until engraftment or up to 90 days.

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria 1. 8 out of 8 matched related or unrelated donor 2. Age > 18 years 3. Good performance status with a Karnofsky score >/= to 70% 4. No evidence of progressive bacterial, viral or fungal infection despite adequate treatment 5. Creatinine clearance > 40 mL/min/1.72m2 6. Total bilirubin < 1.5 and ALT and AST < 2 times the upper limit of normal 7. Cardiac ejection fraction > 40% 8. DLCO > 50% 9. Negative pregnancy test 10. Negative HIV serology 11. Able to provide informed consent 12. 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. 13. 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. Exclusion Criteria: 1. Age <18 years 2. Poor performance status (<70%) 3. Active infections 4. Abnormal creatinine clearance <40ml/min 5. Elevated bilirubin >1.5 and ALT and AST .2 times the upper limit of normal 6. Poor ejection fraction <40% 7. DLCO <50% 8. Pregnant female. 9. HIV positive 10. Inability to provide informed consent 11. Patient has >/= Grade 2 peripheral neuropathy 12. 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. 13. Patient has hypersensitivity to bortezomib, boron, or mannitol. 14. Serious medical or psychiatric illness likely to interfere with participation in this clinical study. 15. 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. 16. Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial.

Additional Information

Official title A Phase I Trial of Post-Transplant Bortezomib and High Dose Cyclophosphamide as Graft-Versus-Host Disease (GVHD) Prophylaxis After Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation (AHSCT)
Principal investigator A. Samer Al-Homsi, MD
Description It is hypothesized that the administration of an early and short course cyclophosphamide and bortezomib after allogeneic hematopoietic stem cell transplantationin in the setting of matched related or unrelated donor transplantation using a standard reduced-intensity conditioning regimen is feasible. The study is a phase I study. The primary objective of the study is to determine the feasibility and safety of increasing doses of bortezomib administered post-transplant in conjunction with fixed high dose cyclophosphamide, also administered post-transplant in the setting of reduced-intensity allogeneic hematopoietic stem cell transplant, as GVHD prophylaxis strategy. Eligible patients will receive a conditioning regimen based on a combination of fludarabine and busulfan with or without rATG.
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Spectrum Health Hospitals.