Trial Search Results

Novel Approaches for Graft-versus-Host Disease Prevention Compared to Contemporary Controls (BMT CTN 1203)

Acute Graft-versus-Host-Disease (GVHD) is an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). This study aims to determine if any of three new GVHD prophylaxis approaches improves the rate of GVHD and relapse free survival at one year after transplant compared to the current standard prophylaxis regimen.

Stanford is currently not accepting patients for this trial.

Lead Sponsor:

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator: National Cancer Institute (NCI)

Intervention(s):

  • Drug: Tacrolimus (ARM with Methotrexate)
  • Drug: Tacrolimus (ARM with MMF and Cyclophosphamide)
  • Drug: Methotrexate (ARM with Maraviroc)
  • Drug: Methotrexate (ARM with Bortezomib)
  • Drug: Maraviroc
  • Drug: Bortezomib
  • Drug: Mycophenolate mofetil
  • Drug: Cyclophosphamide

Phase:

Phase 2

Eligibility


Inclusion Criteria:

   1. Age 18-75 years (patient is older than 18.0 and less than 76.0 years old)

   2. Patients with acute leukemia, chronic myelogenous leukemia or myelodysplasia with no
   circulating blasts and with less than 5% blasts in the bone marrow.

   3. Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, follicular,
   marginal zone, diffuse large B-cell, Hodgkin's Lymphoma,or mantle cell lymphoma with
   chemosensitive disease at time of transplantation

   4. Planned reduced intensity conditioning regimen (see eligible regimens in Table 2.4a)

   5. Patients must have a related or unrelated peripheral blood stem cell donor as follows:

      1. Sibling donor must be a 6/6 match for HLA-A and -B at intermediate (or higher)
      resolution, and -DRB1 at high resolution using DNA-based typing, and must be
      willing to donate peripheral blood stem cells and meet institutional criteria for
      donation.

      2. Unrelated donor must be a 7/8 or 8/8 match at HLA-A, -B, -C and -DRB1 at high
      resolution using DNA-based typing. Unrelated donor must be willing to donate
      peripheral blood stem cells and be medically cleared to donate stem cells
      according to National Marrow Donor Program (NMDP) criteria.

   6. Cardiac function: Ejection fraction at rest ≥ 45%

   7. Estimated creatinine clearance greater than 50 mL/minute (using the Cockcroft-Gault
   formula and actual body weight)

   8. Pulmonary function: Diffusing capacity of the lung for carbon monoxide (DLCO) ≥ 40%
   (adjusted for hemoglobin) and forced expiratory volume in one second (FEV1) ≥ 50%

   9. Liver function: total bilirubin < 1.5 x the upper limit of normal and alanine
   aminotransferase (ALT)/aspartate aminotransferase (AST) < 2.5x the upper normal limit.
   Patients who have been diagnosed with Gilbert's Disease are allowed to exceed the
   defined bilirubin value of 1.5x the upper limit of normal.

10. Female subjects (unless postmenopausal for at least 1 year before the screening visit,
   or surgically sterilized), agree to practice two (2) effective methods of
   contraception at the same time, or agree to completely abstain from heterosexual
   intercourse, from the time of signing the informed consent through 12 months post
   transplant (see Section 2.6.4 for definition of postmenopausal).

11. Male subjects (even if surgically sterilized), of partners of women of childbearing
   potential must agree to one of the following: practice effective barrier contraception
   (see Section 2.6.4 for list of barrier methods), or abstain from heterosexual
   intercourse from the time of signing the informed consent through 12 months post
   transplant.

12. Signed informed consent

Exclusion Criteria:

   1. Prior allogeneic transplant

   2. Karnofsky Performance Score < 70%

   3. Active central nervous system (CNS) involvement by malignant cells

   4. Patients with uncontrolled bacterial, viral or fungal infections (currently taking
   medication and with progression or no clinical improvement) at time of enrollment.

   5. Presence of fluid collection (ascites, pleural or pericardial effusion) that
   interferes with methotrexate clearance or makes methotrexate use contraindicated

   6. Patients with transformed lymphoma (e.g., Richters transformation arising in
   follicular lymphoma or chronic lymphocytic leukemia)

   7. Patients seropositive for the human immunodeficiency virus (HIV)

   8. Patient with active Hepatitis B or C determined by serology and/or nucleic acid
   amplification tests (NAAT)

   9. Patients with hypersensitivity to bortezomib, boron or mannitol

10. Patients with ≥ grade 2 sensory peripheral neuropathy

11. Myocardial infarction within 6 months prior to enrollment or New York Heart
   Association (NYHA) Class III or IV heart failure (see Appendix D), 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.

12. Female patients who are lactating or pregnant

13. Patients with a serious medical or psychiatric illness likely to interfere with
   participation in this clinical study

14. Patients with prior malignancies except resected basal cell carcinoma or treated
   cervical carcinoma in situ. Cancer treated with curative intent ≥ 5 years previously
   will be allowed. Cancer treated with curative intent < 5 years previously will not be
   allowed unless approved by the Protocol Officer or one of the Protocol Chairs.

15. Planned use of anti-thymocyte globulin (ATG) or alemtuzumab in conditioning regimen.

16. Planned post-transplant therapy, including use of tyrosine-kinase inhibitors (TKI).

17. Inability to withhold agents that may interact with hepatic cytochrome P450 enzymes
   (CYP3A4), or glutathione S-transferases involved in bortezomib and/or busulfan
   metabolism during day -5 through day +7. It is acceptable to use alternative
   non-interacting medications during this period, and then resume prior medications.

18. Patients with secondary acute myeloid leukemia arising from myeloproliferative
   disease, including Chronic myelomonocytic leukemia (CMML), with evidence of active
   myeloproliferative features or myelofibrosis in the background.

Ages Eligible for Study

18 Years - 75 Years

Genders Eligible for Study

All

Not currently accepting new patients for this trial

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Physician Referrals
650-723-0822
Not Recruiting