Calcineurin Inhibitor-Free Interventions BMT CTN 1301 for Prevention of Graft-versus-Host Disease (BMT CTN 1301)

Not Recruiting

Trial ID: NCT02345850


The study is designed as a three arm randomized Phase III, multicenter trial comparing two calcineurin inhibitor (CNI)-free strategies for Graft-versus-Host Disease (GVHD) prophylaxis to standard tacrolimus and methotrexate (Tac/Mtx) in patients with hematologic malignancies undergoing myeloablative conditioning hematopoietic stem cell transplantation.

Official Title

A Randomized, Multi-Center, Phase III Trial of Calcineurin Inhibitor-Free Interventions for Prevention of Graft-versus-Host Disease (BMT CTN 1301; Progress II)

Stanford Investigator(s)

Lori Muffly
Lori Muffly

Associate Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)


Inclusion Criteria:

   1. Males and females aged ≥ 1.0 year and < 66.0 years

   2. Patients with acute leukemia in morphologic complete remission with or without
   hematologic recovery or with myelodysplasia (MDS) with no circulating blasts and with
   less than 5% blasts in the bone marrow. Patients with CMML must have a WBC count ≤
   10,000 cells/µL and < 5% blasts in the marrow. Patients with ≥ 5% blasts due to a
   regenerating marrow must contact the protocol chairs for review.

   3. Planned myeloablative conditioning regimen

   4. Patients must have a related or unrelated donor as follows:

      1. Related donor must be an 8/8 match for human leukocyte antigen (HLA)-A, -B, and
      -C at intermediate (or higher) resolution, and -DRB1 at high resolution using
      DNA-based typing. Pediatric related donors must weigh ≥ 25.0 kg., must have
      adequate peripheral venous catheter access for leukapheresis or must agree to
      placement of a central catheter, must be willing to (1) donate bone marrow and
      (2) receive G-CSF followed by donation of peripheral blood stem cells (product to
      be determined by randomization post enrollment) and must meet institutional
      criteria for donation.

      2. Unrelated donor must be an 8/8 match at HLA-A, -B, -C and -DRB1 at high
      resolution using DNA-based typing. Unrelated donor must be medically eligible to
      donate according to National Marrow Donor Program (NMDP) (or equivalent donor
      search organization) criteria. At time of enrollment, the donor should not have
      any known preferences or contraindications to donate bone marrow or peripheral
      blood stem cells. (Selection of unrelated donors is to be performed according to
      institutional practice. It is recommended that the time from collection to
      initiation of the cell processing be considered when prioritizing donors, as data
      shows better results for CD34 selection when cell processing begins within 36
      hours of the end of collection)

   5. Cardiac function: Ejection fraction at rest ≥ 45.0% or shortening fraction of ≥ 27.0%
   by echocardiogram or radionuclide scan (MUGA).

   6. Estimated creatinine clearance (for patients > 12 years) greater than 50.0 mL/minute
   (using the Cockcroft-Gault formula and actual body weight); for pediatric patients (>
   1 year to 12 years), Glomerular Filtration Rate (GFR) estimated by the updated
   Schwartz formula ≥ 90.0 mL/min/1.73 m^2. If the estimated creatinine clearance is < 90
   mL/min/1.73 m^2, then renal function must be measured by 24-hour creatinine clearance
   or nuclear GFR, and must be > 70.0 mL/min/1.73 m^2.

   7. Pulmonary function: Diffusing capacity of the lung for carbon monoxide (DLCO) ≥ 50%
   (adjusted for hemoglobin), and forced expiratory volume in one second (FEV1) or forced
   vital capacity (FVC) ≥ 50%; for children who are unable to perform for Pulmonary
   Function Tests (PFTs) due to age or developmental ability, there must be no evidence
   of dyspnea and no need for supplemental oxygen, as evidenced by O2 saturation ≥ 92% on
   room air.

   8. Liver function: total bilirubin < 2x the upper limit of normal (unless elevated
   bilirubin is attributed to Gilbert's Syndrome) and alanine aminotransferase (ALT) /
   aspartate aminotransferase (AST) < 2.5x the upper limit of normal.

   9. Signed informed consent.

Exclusion Criteria:

   1. Prior autologous or allogeneic hematopoietic stem cell transplant

   2. Karnofsky or Lansky 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 seropositive for HIV-1 or -2

   7. Patients seropositive for Human T-Lymphotrophic Virus (HTLV)-I or -II

   8. Patients with active Hepatitis B or C viral replication by polymerase chain reaction

   9. Documented allergy to iron dextran or murine proteins

10. Women who are pregnant (positive serum or urine βHCG) or breastfeeding

11. Females of childbearing potential (FCBP) or men who have sexual contact with FCBP
   unwilling to use 2 effective forms of birth control or abstinence for one year after

12. History of uncontrolled autoimmune disease or on active treatment

13. Patients with prior malignancies, except resected non-melanoma 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.

14. Patient unable to comply with the treatment protocol including appropriate supportive
   care, follow-up and research tests

15. Planned post-transplant maintenance therapy except for FLT3 inhibitors or TKIs must be
   declared prior to randomization.

16. If it is known prior to enrollment that the hematopoietic stem cell product will need
   to be cryopreserved, the patient should not be enrolled.

17. German centers only: Treatment with any known non-marketed drug substance or
   experimental therapy within 5 terminal half lives or 4 weeks prior to enrollment,
   whichever is longer, or participation in any other interventional clinical study.


procedure: Unmanipulated Bone Marrow Graft with Tacrolimus/Methotrexate

procedure: Mobilized CD34-selected Peripheral Blood Stem Cell graft

procedure: Unmanipulated Bone Marrow Graft with Cyclophosphamide

drug: Cyclophosphamide

drug: Tacrolimus

drug: Methotrexate

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305

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