CClinicalTrials.gg
Sign In
CompletedNCT02208037Updated Jan 23, 2019Results posted

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

A Phase 2 interventional study of Tacrolimus (ARM with Methotrexate) and Tacrolimus (ARM with MMF and Cyclophosphamide) in Acute Leukemia, Chronic Myelogenous Leukemia and Myelodysplasia, sponsored by National Heart, Lung, and Blood Institute (NHLBI). Completed at 30 sites in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2019-01-23.

Sponsored by National Heart, Lung, and Blood Institute (NHLBI) · Phase 2, Interventional, and Prevention

Phase
Phase 2
Study type
Interventional
Enrollment
279
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study summary

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.

Read the detailed description

GVHD is a complication that can occur after a bone marrow or stem cell transplant. The transplant recipient's body is attacked by the newly introduced cells. Only about 40% of patients with acute GVHD have durable responses when treated with corticosteroid therapy. A strategy that helps fewer people suffer from GVHD, without other adverse effects, would be an effective approach to improve survival after allogeneic transplantation.

GVHD incidence can be decreased with various treatment plans. Early transplants were done using post-transplant methotrexate to prevent GVHD. Another drug, cyclosporine, was later shown to work better than methotrexate. Then doctors discovered that the combined use of cyclosporine and methotrexate worked even better than either agent alone. More recently, other calcineurin-inhibitors, such as tacrolimus have been developed as GVHD prophylactic agents due to favorable toxicity profiles in comparison with cyclosporine. Studies have been conducted to compare available treatment combinations for related and unrelated donors. The combination of tacrolimus/methotrexate remains a standard for GVHD prophylaxis.

However, improved GVHD prophylaxis remains a significant clinical need in HSCT. The current clinical trial will test three novel GVHD prophylaxis approaches: tacrolimus/methotrexate and bortezomib (Tac/MTX/Bort), tacrolimus/methotrexate and maraviroc (Tac/MTX/MVC) and tacrolimus/mycophenolate mofetil and cyclophosphamide (Tac/MMF/Cy). This randomized Phase II clinical trial will compare each intervention arm with a Tac/MTX control.

This study will enroll people who have a cancer of the blood or lymph glands and a stem cell transplant is a treatment option. The study will take at least two years and will include 270 participants - 90 participants in each of three treatment groups. The purpose of this study is to compare three combinations of medications to see whether one or more of them are better than the current standard of care (Tacrolimus/Methotrexate) to prevent GVHD.

02

Conditions studied

  • Acute Leukemia
  • Chronic Myelogenous Leukemia
  • Myelodysplasia
  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
  • Lymphoma, B-Cell
  • Lymphoma, Follicular
  • Lymphoma, Large B-Cell, Diffuse
  • Hodgkin's Lymphoma

Keywords

  • Acute Lymphoblastic Leukemia/Lymphoma
  • Acute Myelogenous Leukemia
  • Mantel-Cell Lymphoma
  • Hematopoietic Transplant
  • GVHD Prophylaxis
03

In context

Lymphoma

5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.

This study's enrollment of 279 is above the median of 40 across 4,508 interventional studies indexed under Lymphoma.

Browse Lymphoma studies →

Lead sponsor

National Heart, Lung, and Blood Institute (NHLBI) is the lead sponsor of 1,117 studies on the registry; 71 are open to participants now.

Of its 57 completed or terminated interventional studies of FDA-regulated products, 49 (86%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
279 participants (actual)

Study arms

  • Experimental
    Tacrolimus/Methotrexate/Bortezomib

    Participants will receive specified dosage of three different GVHD prophylaxis agents: Tacrolimus, Methotrexate, and Bortezomib.

    Drug: Tacrolimus (ARM with Methotrexate) · Drug: Methotrexate (ARM with Bortezomib) · Drug: Bortezomib

  • Experimental
    Tacrolimus/Methotrexate/Maraviroc

    Participants will receive specified dosage of three different GVHD prophylaxis agents: Tacrolimus, Methotrexate, and Maraviroc.

    Drug: Tacrolimus (ARM with Methotrexate) · Drug: Methotrexate (ARM with Maraviroc) · Drug: Maraviroc

  • Experimental
    Tacrolimus/MMF/Cyclophosphamide

    Participants will receive specified dosage of three different GVHD prophylaxis agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.

    Drug: Tacrolimus (ARM with MMF and Cyclophosphamide) · Drug: Mycophenolate mofetil · Drug: Cyclophosphamide

Interventions

  • DrugTacrolimus (ARM with Methotrexate)

    Tacrolimus will be given orally at a dose of 0.05 mg/kg or intravenously at a dose of 0.03 mg/kg starting Day -3. The dose of tacrolimus may be rounded to the nearest 0.5 mg for oral formulations. Subsequent dosing will be based on blood levels. The dose should be adjusted accordingly to maintain a suggested level of 5-15 ng/mL. If patients are on medications which alter the metabolism of tacrolimus (e.g. azoles), the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HSCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices but patients should be off tacrolimus by Day 180 post HSCT if there is no evidence of active GVHD.

    Also known as: Prograf®, FK506

  • DrugTacrolimus (ARM with MMF and Cyclophosphamide)

    Tacrolimus will be given orally at a dose of 0.05 mg/kg or intravenously at a dose of 0.03 mg/kg starting Day +5. Serum levels of tacrolimus will be measured at Day 7 and then should be checked weekly thereafter, and the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at a minimum of 90 days post HSCT if there is no evidence of active GVHD. The rate of tapering will be done according to institutional practices but patients should be off tacrolimus by Day 180 post HSCT if there is no evidence of active GVHD.

    Also known as: Prograf®, FK506

  • DrugMethotrexate (ARM with Maraviroc)

    Methotrexate will be administered, per institutional practices, at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. The Day +1 dose of methotrexate will be given at least 24 hours after the hematopoietic stem cell infusion and at least 30 minutes after the first dose of maraviroc. Dose reduction of MTX due to worsening creatinine clearance after initiation of conditioning regimen, high serum levels or development of oral mucositis is allowed according to institutional practices.

    Also known as: MTX

  • DrugMethotrexate (ARM with Bortezomib)

    Methotrexate will be administered, per institutional practices, at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. The Day +1 dose of methotrexate will be given at least 24 hours after the hematopoietic stem cell infusion and at least 30 minutes after the first dose of bortezomib. Dose reduction of MTX due to worsening creatinine clearance after initiation of conditioning regimen, high serum levels or development of oral mucositis is allowed according to institutional practices.

    Also known as: MTX

  • DrugMaraviroc

    Maraviroc will be dosed at 300 mg orally twice a day and will start on Day -3 prior to hematopoietic stem cell infusion, and continue until Day 30 post HSCT. If the patient requires a two-day stem cell infusion, maraviroc treatment will end 30 days after the first infusion day.

    Also known as: Selzentry®

  • DrugBortezomib

    Bortezomib will be administered at the dose of 1.3 mg/m2 based upon actual body weight (ABW) as an approximately 3-5 second IV push on Days +1, +4, and +7 after hematopoietic stem cell infusion. There must be at least 72 hours between each dose of bortezomib. Subcutaneous administration of bortezomib is not allowed on this protocol.

    Also known as: Velcade®

  • DrugMycophenolate mofetil

    MMF will be given at a dose of 15 mg/kg three times a day (TID) based upon ABW with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day 5 and discontinue after the last dose on Day 35, or may be continued if active GVHD is present.

    Also known as: Cellcept®

  • DrugCyclophosphamide

    Hydration prior to cyclophosphamide may be given according to institutional standards. Mesna will be given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post-cyclophosphamide or administered per institutional standards. Mesna dose will be based on the cyclophosphamide dose being given. The total daily dose of Mesna is equal to 80% of the total daily dose of cyclophosphamide. Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if ABW \< IBW, use ABW\] will be given on Day 3 post-transplant (between 60 and 72 hours after the start of the HSCT) and on Day 4 post-transplant (approximately 24 hours after Day 3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours (depending on volume).

    Also known as: Cytoxan®

06

What researchers measure

Primary outcomes

  1. Percentage of Participants With GVHD/Relapse or Progression-free Survival (GRFS)

    GRFS is defined as being free of grade III-IV acute GVHD onset, chronic GVHD onset requiring systemic immunosuppressive therapy, disease relapse or progression, and death from any cause.

    Time frame: 1 Year Post-transplant

Secondary outcomes

  1. Percentage of Participants With Grade II-IV Acute GVHD

    Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995: Skin stage: 0: No rash 1. Rash \<25% of body surface area 2. Rash on 25-50% of body surface area 3. Rash on \> 50% of body surface area 4. Generalized erythroderma with bullous formation Liver stage (based on bilirubin level)\*: 0: \<2 mg/dL 1. 2-3 mg/dL 2. 3.01-6 mg/dL 3. 6.01-15.0 mg/dL 4. \>15 mg/dL GI stage\*: 0: No diarrhea or diarrhea \<500 mL/day 1. Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD 2. Diarrhea 1000-1499 mL/day 3. Diarrhea \>1500 mL/day 4. Severe abdominal pain with or without ileus \* If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1. GVHD grade: 0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4

    Time frame: Day 180 Post-transplant

  2. Percentage of Participants With Grade III-IV Acute GVHD

    Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995: Skin stage: 0: No rash 1. Rash \<25% of body surface area 2. Rash on 25-50% of body surface area 3. Rash on \> 50% of body surface area 4. Generalized erythroderma with bullous formation Liver stage (based on bilirubin level)\*: 0: \<2 mg/dL 1.2-3 mg/dL 2.3.01-6 mg/dL 3.6.01-15.0 mg/dL 4.\>15 mg/dL GI stage\*: 0: No diarrhea or diarrhea \<500 mL/day 1. Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD 2. Diarrhea 1000-1499 mL/day 3. Diarrhea \>1500 mL/day 4. Severe abdominal pain with or without ileus \* If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1. GVHD grade: 0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4

    Time frame: Day 180 Post-transplant

  3. Percentage of Participants With Chronic GVHD

    Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe. Occurrence of chronic GVHD is defined as the occurrence of mild, moderate, or severe chronic GVHD per this classification.

    Time frame: 1 Year Post-transplant

  4. Percentage of Participants With Chronic GVHD Requiring Immunosupressive Therapy

    Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe. Occurrence of chronic GVHD is defined as the occurrence of mild, moderate, or severe chronic GVHD per this classification. This endpoint considers the occurrence of chronic GVHD that necessitated initiation of immunosuppressive therapy for treatment.

    Time frame: 1 Year Post-transplant

  5. Percentage of Participants With Disease Relapse or Progression

    Relapse is defined by either morphological or cytogenetic evidence of acute leukemia or MDS consistent with pretransplant features, or radiologic evidence of lymphoma. Progression of disease applies to patients with lymphoproliferative diseases (lymphoma or chronic lymphocytic leukemia) not in remission prior to transplantation and is defined as increase in size of prior sites of disease or evidence of new sites of disease.

    Time frame: 1 Year Post-transplant

  6. Percentage of Participants With Transplant-Related Mortality (TRM)

    TRM is defined as death without prior disease relapse or progression.

    Time frame: 1 Year Post-transplant

  7. Percentage of Participants With Disease-free Survival

    Disease-free survival is defined as being alive and free of disease relapse or progression.

    Time frame: 1 Year Post-transplant

  8. Percentage of Participants With GVHD-free Survival

    GVHD-free survival is defined as being alive without previous onset of Grade III-IV acute GVHD or chronic GVHD requiring immunosuppressive therapy.

    Time frame: 1 Year Post-transplant

  9. Percentage of Participants With Overall Survival

    Time frame: 1 Year Post-transplant

  10. Percentage of Participants With Neutrophil Recovery

    Neutrophil recovery is defined as achieving an absolute neutrophil count (ANC) ≥ 500/mm\^3 for three consecutive measurements on three different days.

    Time frame: Days 28 and 100 Post-transplant

  11. Percentage of Participants With Platelet Recovery

    Platelet recovery is defined as the first day of a sustained platelet count \>20,000/mm\^3 with no platelet transfusion in the preceding seven days.

    Time frame: Days 60 and 100 Post-transplant

  12. Donor Cell Engraftment

    Donor cell engraftment will be assessed with donor/recipient chimerism. Chimerism may be evaluated in bone marrow, whole blood, or CD3 fractions. Full donor chimerism is defined as the presence of ≥ 95% of donor cells as a proportion of total cells. Mixed chimerism is defined as the presence of donor cells, as a proportion of total cells, of \< 95% but \> 5% in the bone marrow or peripheral blood. Full and mixed chimerism will be evidence of donor cell engraftment. Donor cells of ≤ 5% will be considered as graft rejection.

    Time frame: Days 28 and 100 Post-transplant

  13. Primary Cause of Death

    Time frame: 1 Year Post-transplant

07

Results

Posted Jan 23, 2019

Participant flow

Participant flow — Overall Study
MilestoneTacrolimus/Methotrexate/BortezomibTacrolimus/Methotrexate/MaravirocTacrolimus/MMF/Cyclophosphamide
Started939393
Completed899292
Not completed411

Outcome measures

PrimaryPercentage of Participants With GVHD/Relapse or Progression-free Survival (GRFS)

GRFS is defined as being free of grade III-IV acute GVHD onset, chronic GVHD onset requiring systemic immunosuppressive therapy, disease relapse or progression, and death from any cause.

Time frame:
1 Year Post-transplant
Reported as:
Number · percentage of participants
Percentage of Participants With GVHD/Relapse or Progression-free Survival (GRFS)
percentage of participantsTacrolimus/Methotrexate/BortezomibTacrolimus/Methotrexate/MaravirocTacrolimus/MMF/Cyclophosphamide
Percentage of Participants With GVHD/Relapse or Progression-free Survival (GRFS)35.5 (27.2 to 43.9)27.2 (19.9 to 35.0)44.1 (35.3 to 52.4)
SecondaryPercentage of Participants With Grade II-IV Acute GVHD

Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995: Skin stage: 0: No rash 1. Rash \<25% of body surface area 2. Rash on 25-50% of body surface area 3. Rash on \> 50% of body surface area 4. Generalized erythroderma with bullous formation Liver stage (based on bilirubin level)\*: 0: \<2 mg/dL 1. 2-3 mg/dL 2. 3.01-6 mg/dL 3. 6.01-15.0 mg/dL 4. \>15 mg/dL GI stage\*: 0: No diarrhea or diarrhea \<500 mL/day 1. Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD 2. Diarrhea 1000-1499 mL/day 3. Diarrhea \>1500 mL/day 4. Severe abdominal pain with or without ileus \* If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1. GVHD grade: 0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4

Time frame:
Day 180 Post-transplant
Reported as:
Number · percentage of participants
Percentage of Participants With Grade II-IV Acute GVHD
percentage of participantsTacrolimus/Methotrexate/BortezomibTacrolimus/Methotrexate/MaravirocTacrolimus/MMF/Cyclophosphamide
Percentage of Participants With Grade II-IV Acute GVHD26 (19 to 34)32 (24 to 40)27 (20 to 35)
SecondaryPercentage of Participants With Grade III-IV Acute GVHD

Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995: Skin stage: 0: No rash 1. Rash \<25% of body surface area 2. Rash on 25-50% of body surface area 3. Rash on \> 50% of body surface area 4. Generalized erythroderma with bullous formation Liver stage (based on bilirubin level)\*: 0: \<2 mg/dL 1.2-3 mg/dL 2.3.01-6 mg/dL 3.6.01-15.0 mg/dL 4.\>15 mg/dL GI stage\*: 0: No diarrhea or diarrhea \<500 mL/day 1. Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD 2. Diarrhea 1000-1499 mL/day 3. Diarrhea \>1500 mL/day 4. Severe abdominal pain with or without ileus \* If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1. GVHD grade: 0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4

Time frame:
Day 180 Post-transplant
Reported as:
Number · percentage of participants
Percentage of Participants With Grade III-IV Acute GVHD
percentage of participantsTacrolimus/Methotrexate/BortezomibTacrolimus/Methotrexate/MaravirocTacrolimus/MMF/Cyclophosphamide
Percentage of Participants With Grade III-IV Acute GVHD8 (4 to 13)9 (4 to 14)2 (0 to 5)
SecondaryPercentage of Participants With Chronic GVHD

Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe. Occurrence of chronic GVHD is defined as the occurrence of mild, moderate, or severe chronic GVHD per this classification.

Time frame:
1 Year Post-transplant
Reported as:
Number · percentage of participants
Percentage of Participants With Chronic GVHD
percentage of participantsTacrolimus/Methotrexate/BortezomibTacrolimus/Methotrexate/MaravirocTacrolimus/MMF/Cyclophosphamide
Percentage of Participants With Chronic GVHD39 (30 to 48)43 (35 to 52)28 (20 to 36)
SecondaryPercentage of Participants With Chronic GVHD Requiring Immunosupressive Therapy

Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe. Occurrence of chronic GVHD is defined as the occurrence of mild, moderate, or severe chronic GVHD per this classification. This endpoint considers the occurrence of chronic GVHD that necessitated initiation of immunosuppressive therapy for treatment.

Time frame:
1 Year Post-transplant
Reported as:
Number · percentage of participants
Percentage of Participants With Chronic GVHD Requiring Immunosupressive Therapy
percentage of participantsTacrolimus/Methotrexate/BortezomibTacrolimus/Methotrexate/MaravirocTacrolimus/MMF/Cyclophosphamide
Percentage of Participants With Chronic GVHD Requiring Immunosupressive Therapy29 (22 to 38)33 (25 to 41)22 (15 to 30)
SecondaryPercentage of Participants With Disease Relapse or Progression

Relapse is defined by either morphological or cytogenetic evidence of acute leukemia or MDS consistent with pretransplant features, or radiologic evidence of lymphoma. Progression of disease applies to patients with lymphoproliferative diseases (lymphoma or chronic lymphocytic leukemia) not in remission prior to transplantation and is defined as increase in size of prior sites of disease or evidence of new sites of disease.

Time frame:
1 Year Post-transplant
Reported as:
Number · percentage of participants
Percentage of Participants With Disease Relapse or Progression
percentage of participantsTacrolimus/Methotrexate/BortezomibTacrolimus/Methotrexate/MaravirocTacrolimus/MMF/Cyclophosphamide
Percentage of Participants With Disease Relapse or Progression24 (17 to 32)31 (23 to 39)28 (21 to 37)
SecondaryPercentage of Participants With Transplant-Related Mortality (TRM)

TRM is defined as death without prior disease relapse or progression.

Time frame:
1 Year Post-transplant
Reported as:
Number · percentage of participants
Percentage of Participants With Transplant-Related Mortality (TRM)
percentage of participantsTacrolimus/Methotrexate/BortezomibTacrolimus/Methotrexate/MaravirocTacrolimus/MMF/Cyclophosphamide
Percentage of Participants With Transplant-Related Mortality (TRM)17 (11 to 24)16 (10 to 23)11 (6 to 17)
SecondaryPercentage of Participants With Disease-free Survival

Disease-free survival is defined as being alive and free of disease relapse or progression.

Time frame:
1 Year Post-transplant
Reported as:
Number · percentage of participants
Percentage of Participants With Disease-free Survival
percentage of participantsTacrolimus/Methotrexate/BortezomibTacrolimus/Methotrexate/MaravirocTacrolimus/MMF/Cyclophosphamide
Percentage of Participants With Disease-free Survival58 (49 to 66)56 (47 to 64)60 (51 to 68)
SecondaryPercentage of Participants With GVHD-free Survival

GVHD-free survival is defined as being alive without previous onset of Grade III-IV acute GVHD or chronic GVHD requiring immunosuppressive therapy.

Time frame:
1 Year Post-transplant
Reported as:
Number · percentage of participants
Percentage of Participants With GVHD-free Survival
percentage of participantsTacrolimus/Methotrexate/BortezomibTacrolimus/Methotrexate/MaravirocTacrolimus/MMF/Cyclophosphamide
Percentage of Participants With GVHD-free Survival43 (34 to 52)34 (26 to 42)53 (44 to 61)
SecondaryPercentage of Participants With Overall Survival
Time frame:
1 Year Post-transplant
Reported as:
Number · percentage of participants
Percentage of Participants With Overall Survival
percentage of participantsTacrolimus/Methotrexate/BortezomibTacrolimus/Methotrexate/MaravirocTacrolimus/MMF/Cyclophosphamide
Percentage of Participants With Overall Survival68 (59 to 76)66 (57 to 74)71 (63 to 78)
SecondaryPercentage of Participants With Neutrophil Recovery

Neutrophil recovery is defined as achieving an absolute neutrophil count (ANC) ≥ 500/mm\^3 for three consecutive measurements on three different days.

Time frame:
Days 28 and 100 Post-transplant
Reported as:
Number · percentage of participants
Percentage of Participants With Neutrophil Recovery
percentage of participantsTacrolimus/Methotrexate/BortezomibTacrolimus/Methotrexate/MaravirocTacrolimus/MMF/Cyclophosphamide
Day 2894 (89 to 98)93 (89 to 97)95 (90 to 98)
Day 10096 (91 to 99)95 (90 to 98)98 (94 to 100)
SecondaryPercentage of Participants With Platelet Recovery

Platelet recovery is defined as the first day of a sustained platelet count \>20,000/mm\^3 with no platelet transfusion in the preceding seven days.

Time frame:
Days 60 and 100 Post-transplant
Reported as:
Number · percentage of participants
Percentage of Participants With Platelet Recovery
percentage of participantsTacrolimus/Methotrexate/BortezomibTacrolimus/Methotrexate/MaravirocTacrolimus/MMF/Cyclophosphamide
Day 6091 (85 to 96)92 (87 to 96)90 (84 to 95)
Day 10091 (85 to 96)92 (87 to 96)96 (91 to 99)
SecondaryDonor Cell Engraftment

Donor cell engraftment will be assessed with donor/recipient chimerism. Chimerism may be evaluated in bone marrow, whole blood, or CD3 fractions. Full donor chimerism is defined as the presence of ≥ 95% of donor cells as a proportion of total cells. Mixed chimerism is defined as the presence of donor cells, as a proportion of total cells, of \< 95% but \> 5% in the bone marrow or peripheral blood. Full and mixed chimerism will be evidence of donor cell engraftment. Donor cells of ≤ 5% will be considered as graft rejection.

Time frame:
Days 28 and 100 Post-transplant
Reported as:
Count of participants · Participants
Donor Cell Engraftment
ParticipantsTacrolimus/Methotrexate/BortezomibTacrolimus/Methotrexate/MaravirocTacrolimus/MMF/Cyclophosphamide
Day 28 — Full Chimerism585664
Day 28 — Mixed Chimerism11108
Day 28 — Graft Rejection112
Day 28 — Dead240
Day 28 — No Assay Performed172118
Day 100 — Full Chimerism635662
Day 100 — Mixed Chimerism141713
Day 100 — Graft Rejection533
Day 100 — Dead4105
Day 100 — No Assay Performed369
SecondaryPrimary Cause of Death
Time frame:
1 Year Post-transplant
Reported as:
Count of participants · Participants
Primary Cause of Death
ParticipantsTacrolimus/Methotrexate/BortezomibTacrolimus/Methotrexate/MaravirocTacrolimus/MMF/Cyclophosphamide
Recurrence/Persistence111215
Acute GVHD372
Chronic GVHD211
Infection474
Organ Failure222
Hemorrhage101
Interstitial Pneumonia101
Adult Respiratory Distress Syndrome210
Metastatis Breast Cancer100
Squamous Cell Carcinoma100
Toxicity - Not Specified010
Still Alive616166

Adverse events

Collected over Up to 1 Year Post-transplant. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Tacrolimus/Methotrexate/Bortezomib30/93 (32.3%)21/93 (22.6%)0/93 (0%)
Tacrolimus/Methotrexate/Maraviroc31/93 (33.3%)14/93 (15.1%)0/93 (0%)
Tacrolimus/MMF/Cyclophosphamide27/93 (29%)12/93 (12.9%)0/93 (0%)
Most frequent serious events
Showing 10 of 37
Most frequent serious events
EventTacrolimus/Methotrexate/BortezomibTacrolimus/Methotrexate/MaravirocTacrolimus/MMF/Cyclophosphamide
CholecystitisHepatobiliary disorders0/930/932/93
ArthralgiaMusculoskeletal and connective tissue disorders2/930/930/93
Respiratory failureRespiratory, thoracic and mediastinal disorders1/932/930/93
Atrial fibrillationCardiac disorders0/931/930/93
Cardiac ArrestCardiac disorders0/931/931/93
Cardiac failureCardiac disorders0/930/931/93
Cardiogenic shockCardiac disorders1/930/930/93
CardiomyopathyCardiac disorders0/931/930/93
Myocardial ischaemiaCardiac disorders1/930/930/93
Pericardial effusionCardiac disorders0/930/931/93

Baseline characteristics

Age, Continuous
Age, Continuous(years)Tacrolimus/Methotrexate/BortezomibTacrolimus/Methotrexate/MaravirocTacrolimus/MMF/CyclophosphamideTotal
Median64 (28 to 76)64 (24 to 74)64 (25 to 75)64 (24 to 76)
Sex: Female, Male
Sex: Female, Male(Participants)Tacrolimus/Methotrexate/BortezomibTacrolimus/Methotrexate/MaravirocTacrolimus/MMF/CyclophosphamideTotal
Female31373098
Male585562175
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Tacrolimus/Methotrexate/BortezomibTacrolimus/Methotrexate/MaravirocTacrolimus/MMF/CyclophosphamideTotal
Hispanic or Latino13711
Not Hispanic or Latino858681252
Unknown or Not Reported33410
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Tacrolimus/Methotrexate/BortezomibTacrolimus/Methotrexate/MaravirocTacrolimus/MMF/CyclophosphamideTotal
American Indian or Alaska Native0000
Asian2316
Native Hawaiian or Other Pacific Islander0000
Black or African American3137
White798182242
More than one race1012
Unknown or Not Reported47516
HCT-CI Comorbidity Index
HCT-CI Comorbidity Index(Participants)Tacrolimus/Methotrexate/BortezomibTacrolimus/Methotrexate/MaravirocTacrolimus/MMF/CyclophosphamideTotal
024182668
1-231372795
3 or greater343739110
Karnofsky Performance Score
Karnofsky Performance Score(Participants)Tacrolimus/Methotrexate/BortezomibTacrolimus/Methotrexate/MaravirocTacrolimus/MMF/CyclophosphamideTotal
10013101134
90393942120
8029272884
708161135
HLA Matching and Donor Type
HLA Matching and Donor Type(Participants)Tacrolimus/Methotrexate/BortezomibTacrolimus/Methotrexate/MaravirocTacrolimus/MMF/CyclophosphamideTotal
Matched Sibling (6/6)29332991
Matched Other Relative (6/6)1146
Matched Unrelated (8/8)534850151
Mismatched Unrelated (7/8)610925
Primary Diagnosis
Primary Diagnosis(Participants)Tacrolimus/Methotrexate/BortezomibTacrolimus/Methotrexate/MaravirocTacrolimus/MMF/CyclophosphamideTotal
Acute Myeloid Leukemia (AML)464949144
Acute Lymphoblastic Leukemia (ALL)1211831
Chronic Myelogeneous Leukemia (CML)2237
Chronic Lymphocytic Leukemia (CLL)2305
Myelodysplastic Syndrome (MDS)16151748
Follicular Lymphoma36514
Diffuse Large B-Cell Lymphoma41712
Mantle Cell Lymphoma4419
Hodgkin's Lymphoma0123

3 further baseline measures are reported on the registry.

08

Study locations

30 sites
  • City of Hope National Medical Center
    Duarte, California 91010, United States
  • Stanford Hospital and Clinics
    Stanford, California 94305, United States
  • University of Florida College of Medicine (Shands)
    Gainesville, Florida 32611, United States
  • H. Lee Moffitt Cancer Center
    Tampa, Florida 33624, United States
  • Emory University
    Atlanta, Georgia 30322, United States
  • BMT Program at Northside Hospital
    Atlanta, Georgia 30342, United States
  • Loyola University Medical Center
    Maywood, Illinois 60153, United States
  • University of Iowa Hospitals and Clinics
    Iowa City, Iowa 52242, United States
  • University of Kansas Hospital
    Westwood, Kansas 66205, United States
  • Johns Hopkins University
    Baltimore, Maryland 22218, United States
  • Dana Farber Cancer Institute/Massachusetts General Hospital
    Boston, Massachusetts 02114, United States
  • Dana Farber Cancer Institute/Brigham & Women's
    Boston, Massachusetts 02215, United States
  • Karmanos Cancer Institute/BMT
    Detroit, Michigan 48201, United States
  • University of Minnesota
    Minneapolis, Minnesota 55455, United States
  • Mayo Clinic - Rochester
    Rochester, Minnesota 55905, United States
  • Washington University/Barnes Jewish Hospital
    Saint Louis, Missouri 63130, United States
  • University of Nebraska Medical Center
    Omaha, Nebraska 68198, United States
  • Roswell Park Cancer Institute
    Buffalo, New York 14263, United States
  • Memorial Sloan-Kettering Cancer Center
    Manhattan, New York 10065, United States
  • University of North Carolina Hospital at Chapel Hill
    Chapel Hill, North Carolina 27514, United States
  • Cleveland Clinic Foundation
    Cleveland, Ohio 44106, United States
  • University Hospitals of Cleveland/Case Western
    Cleveland, Ohio 44106, United States
  • Ohio State/Arthur G. James Cancer Hospital
    Columbus, Ohio 43210, United States
  • Oregon Health & Science University
    Portland, Oregon 97239, United States
  • University of Pennsylvania Cancer Center
    Philadelphia, Pennsylvania 19104, United States
  • Medical University of South Carolina
    Charleston, South Carolina 29425, United States
  • University of Texas/MD Anderson Cancer Center
    Houston, Texas 77030, United States
  • Texas Transplant Institute
    San Antonio, Texas 78229, United States
  • University of Utah Med School
    Salt Lake City, Utah 84112, United States
  • Virginia Commonwealth University MCV Hospitals
    Richmond, Virginia 23284, United States
09

References and documents

Publications

  • Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995 Jun;15(6):825-8. PubMed 7581076 ↗
  • Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56. doi: 10.1016/j.bbmt.2005.09.004. PubMed 16338616 ↗
  • Bolanos-Meade J, Reshef R, Fraser R, Fei M, Abhyankar S, Al-Kadhimi Z, Alousi AM, Antin JH, Arai S, Bickett K, Chen YB, Damon LE, Efebera YA, Geller NL, Giralt SA, Hari P, Holtan SG, Horowitz MM, Jacobsohn DA, Jones RJ, Liesveld JL, Logan BR, MacMillan ML, Mielcarek M, Noel P, Pidala J, Porter DL, Pusic I, Sobecks R, Solomon SR, Weisdorf DJ, Wu J, Pasquini MC, Koreth J. Three prophylaxis regimens (tacrolimus, mycophenolate mofetil, and cyclophosphamide; tacrolimus, methotrexate, and bortezomib; or tacrolimus, methotrexate, and maraviroc) versus tacrolimus and methotrexate for prevention of graft-versus-host disease with haemopoietic cell transplantation with reduced-intensity conditioning: a randomised phase 2 trial with a non-randomised contemporaneous control group (BMT CTN 1203). Lancet Haematol. 2019 Mar;6(3):e132-e143. doi: 10.1016/S2352-3026(18)30221-7. PubMed 30824040 ↗

Study documents

  • Study protocol · Jul 17, 2015
  • Statistical analysis plan · Nov 9, 2016

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Results will be published in a manuscript and supporting information submitted to NIH BioLINCC (including data dictionaries, case report forms, data submission documentation, documentation for outcomes dataset, etc where indicated).

Supporting information: Study protocol

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 23, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02208037
Lead sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Collaborators
Blood and Marrow Transplant Clinical Trials Network, National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Aug 4, 2014
Start date
Aug 2014
Primary completion
Oct 2017
Completion
Oct 2017
Results posted
Jan 23, 2019
Last update
Jan 23, 2019

Study contacts

Mary Horowitz, MD
study director · Center for International Blood and Marrow Transplant Research

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Dec 2017. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Lymphoma→

Other studies from this sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Start the discussion