Clinical trial NCT01860170: Post-Transplant Bortezomib and High Dose Cyclophosphamide as Graft-Versus-Host Disease (GVHD) Prophylaxis
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hematological Malignancy
Keywords: Blood and Marrow Transplant (BMT)
MRD
MUD
GVHD
Lead sponsor: Spectrum Health Hospitals
Sponsor class: OTHER
Collaborators: name: Millennium Pharmaceuticals, Inc.
First posted: 2013-05-22
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose Limiting Toxicity
timeFrame: Assessed daily (while inpatient) through clinical and laboratory examination up to 90 days.
Secondary outcomes:
measure: Engraftment
timeFrame: Assessed daily by laboratory evaluation until engraftment or up to 90 days.
Other outcomes:
measure: GVHD
timeFrame: 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.
Locations:
city: Grand Rapids
country: United States
facility: Spectrum Health
state: Michigan
Study officials:
affiliation: Spectrum Health Hospitals
name: A. Samer Al-Homsi, MD
role: PRINCIPAL_INVESTIGATOR
References: