Hematological MalignancyPhase 1/2NCT01860170
Post-Transplant Bortezomib and High Dose Cyclophosphamide as Graft-Versus-Host Disease (GVHD) Prophylaxis
A Phase 1/2 study testing Cohort 1-Bortezomib (Velcade ®), Cohort 2-Bortezomib (Velcade ®) and Cohort 3-Bortezomib (Velcade ®) in people with Hematological Malignancy, run by Corewell Health West at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematological Malignancy
- What is being tested?
- Cohort 1-Bortezomib (Velcade ®), Cohort 2-Bortezomib (Velcade ®) and Cohort 3-Bortezomib (Velcade ®)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2012to Mar 2018
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 8 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
Show all 13Show fewer
- 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.
Who cannot join
- 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%
Show all 16Show fewer
- 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.
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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)
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.
Read the detailed 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.
- Conditions
- Hematological Malignancy
- Being tested
- Cohort 1-Bortezomib (Velcade ®), Cohort 2-Bortezomib (Velcade ®), Cohort 3-Bortezomib (Velcade ®)
- Keywords
- Blood and Marrow Transplant (BMT), MRD, MUD, GVHD
- Medical subject headings
- Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cohort 1-Bortezomib (Velcade ®)Drug
Also called Cyclophosphamide (Cytoxan ®), Bortezomib (Velcade ®)
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.
Cohort 2-Bortezomib (Velcade ®)Drug
Also called Cyclophosphamide (Cytoxan ®), Bortezomib (Velcade ®)
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.
Cohort 3-Bortezomib (Velcade ®)Drug
Also called Cyclophosphamide (Cytoxan ®), Bortezomib (Velcade ®)
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Cohort 3-Bortezomib (Velcade ®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Assessed daily (while inpatient) through clinical and laboratory examination up to 90 days.
Secondary outcomes (1)
Engraftment
Neutrophil engraftment is defined as achieving an absolute neutrophil count (ANC) > 0.5 109/L for 3 consecutive measurements on different days. The first of the 3 days will be considered the day of neutrophil engraftment.
Platelet engraftment is defined as platelet count > 20 109/L for 3 consecutive measurements over at least 3 days. The first of the 3 days will be considered the day of platelet engraftment.
In this study, graft failure is defined as lack of achieving neutrophil engraftment by day 22 and donor chimerism > 50% by day 45.
Measured: Assessed daily by laboratory evaluation until engraftment or up to 90 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2013 (estimated)
- Study startApr 2012
- Primary completionMar 2016
- Study completionMar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hematological MalignancyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Corewell Health West
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- A. Samer Al-Homsi, MD, Principal investigator, Corewell Health West
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01860170
- Sponsor's protocol ID
- 2013-083
- Status last verified
- May 2023
- First submitted
- 14 May 2013
- Last updated
- 2 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01860170
- Acronym / sponsor ID
- 2013-083
- Conditions
- Hematological Malignancy
- Keywords
- Blood and Marrow Transplant (BMT), MRD, MUD, GVHD
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Corewell Health WestUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Study start
- Apr 2012 (actual)
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2018 (actual)
- First posted
- 22 May 2013 (estimated)
- Results
- Posted 17 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1-Bortezomib (Velcade®) | Active comparator | Drug: Cohort 1-Bortezomib (Velcade ®)Bortezomib (Velcade®) 0.7 mg/m2 rapid IV push on days 0 (at least 6 hours after transplant) and +3. |
| Cohort 2-Bortezomib (Velcade®) | Active comparator | Drug: Cohort 2-Bortezomib (Velcade ®)Bortezomib (Velcade®) 1 mg/ m2 rapid IV push on days 0 (at least 6 hours after transplant) and +3. |
| Cohort 3-Bortezomib (Velcade®) | Active comparator | Drug: Cohort 3-Bortezomib (Velcade ®)Bortezomib (Velcade®) 1.3 mg/m2 rapid IV push on days 0 (at least 6 hours after transplant) and +3. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 8 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cohort 1-Bortezomib (Velcade ®)Also: Cyclophosphamide (Cytoxan ®), Bortezomib (Velcade ®)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. | Drug | Cohort 1-Bortezomib (Velcade®) |
| Cohort 2-Bortezomib (Velcade ®)Also: Cyclophosphamide (Cytoxan ®), Bortezomib (Velcade ®)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. | Drug | Cohort 2-Bortezomib (Velcade®) |
| Cohort 3-Bortezomib (Velcade ®)Also: Cyclophosphamide (Cytoxan ®), Bortezomib (Velcade ®)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. | Drug | Cohort 3-Bortezomib (Velcade®) |
Primary outcome
Dose Limiting Toxicity
Time frame: Assessed daily (while inpatient) through clinical and laboratory examination up to 90 days.
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
1 secondary outcome
Engraftment
Time frame: Assessed daily by laboratory evaluation until engraftment or up to 90 days.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Hematological Malignancy
Not yet recruitingPhase 4
MACE and BTK Inhibitors
Hematologic Cancer, MACE
RecruitingEarly Phase 1
HMCT/CT2401: Abatacept GVHD Prophylaxis Following Omidubicel HCT
Hematologic Malignancy
Recruiting
An Exploratory Study to Evaluate Immune Determinants of the Response to Adoptive Cell Therapy (ACT) in Solid and Hematologic Tumors
Solid Tumor, Adult, Solid Tumor, Childhood
RecruitingObservational study
Natural History Study to Determine Drug Metabolism Phenotype and Appropriate Germline Source DNA in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant
Leukemia, Lymphoma
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
A. Samer Al-Homsi, MD principal investigator
Corewell Health West
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Cohort 1-Bortezomib (Velcade ®), Cohort 2-Bortezomib (Velcade ®) and Cohort 3-Bortezomib (Velcade ®) in people with Hematological Malignancy, run by Corewell Health West at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Limiting Toxicity (time frame: Assessed daily (while inpatient) through clinical and laboratory examination up to 90 days.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2023.