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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)

Phase 1
18 Years
Not Enrolling
Hematological Malignancy

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Trial Information

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)

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.

Inclusion 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

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

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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Outcome Measure:

Dose Limiting Toxicity

Outcome Description:

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

Outcome Time Frame:

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

Safety Issue:


Principal Investigator

A. Samer Al-Homsi, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Spectrum Health Hospitals


United States: Food and Drug Administration

Study ID:




Start Date:

April 2012

Completion Date:

Related Keywords:

  • Hematological Malignancy
  • Blood and Marrow Transplant (BMT)
  • MRD
  • MUD
  • GVHD
  • Neoplasms
  • Graft vs Host Disease
  • Hematologic Neoplasms



Spectrum Health Grand Rapids, Michigan  49503