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

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT02208037
• Collaborator: Blood and Marrow Transplant Clinical Trials Network (Other), National Cancer Institute (NCI) (NIH)
• Enrollment: 279
• Locations: 30
• Arms: 3
• Duration (Months): 38
• Patients Per Site: 9.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
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	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 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 279 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Multi-center Phase II Trial Randomizing Novel Approaches for Graft-versus-Host Disease Prevention Compared to Contemporary Controls (BMT CTN #1203; Progress I)
• Study Start Date: Aug 1, 2014
• Actual Primary Completion Date: Oct 1, 2017
• Actual Study Completion Date: Oct 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tacrolimus/Methotrexate/Bortezomib Participants will receive specified dosage of three different GVHD prophylaxis agents: Tacrolimus, Methotrexate, and Bortezomib.	Drug: Tacrolimus (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.; Other Names: Prograf® FK506 ; Drug: Methotrexate (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.; Other Names: MTX ; Drug: Bortezomib; 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.; Other Names: Velcade®
Experimental: Tacrolimus/Methotrexate/Maraviroc Participants will receive specified dosage of three different GVHD prophylaxis agents: Tacrolimus, Methotrexate, and Maraviroc.	Drug: Tacrolimus (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.; Other Names: Prograf® FK506 ; Drug: Methotrexate (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.; Other Names: MTX ; Drug: Maraviroc; 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.; Other Names: Selzentry®
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); 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.; Other Names: Prograf® FK506 ; Drug: Mycophenolate 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.; Other Names: Cellcept® ; Drug: Cyclophosphamide; 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).; Other Names: Cytoxan®

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With GVHD/Relapse or Progression-free Survival (GRFS) [1 Year Post-transplant]

   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.

Secondary Outcome Measures

1. Percentage of Participants With Grade II-IV Acute GVHD [Day 180 Post-transplant]

   Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995: Skin stage: 0: No rash Rash <25% of body surface area Rash on 25-50% of body surface area Rash on > 50% of body surface area Generalized erythroderma with bullous formation Liver stage (based on bilirubin level)*: 0: <2 mg/dL 2-3 mg/dL 3.01-6 mg/dL 6.01-15.0 mg/dL >15 mg/dL GI stage*: 0: No diarrhea or diarrhea <500 mL/day Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD Diarrhea 1000-1499 mL/day Diarrhea >1500 mL/day 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

2. Percentage of Participants With Grade III-IV Acute GVHD [Day 180 Post-transplant]

   Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995: Skin stage: 0: No rash Rash <25% of body surface area Rash on 25-50% of body surface area Rash on > 50% of body surface area 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 Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD Diarrhea 1000-1499 mL/day Diarrhea >1500 mL/day 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

3. Percentage of Participants With Chronic GVHD [1 Year Post-transplant]

   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.

4. Percentage of Participants With Chronic GVHD Requiring Immunosupressive Therapy [1 Year Post-transplant]

   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.

5. Percentage of Participants With Disease Relapse or Progression [1 Year Post-transplant]

   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.

6. Percentage of Participants With Transplant-Related Mortality (TRM) [1 Year Post-transplant]

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

7. Percentage of Participants With Disease-free Survival [1 Year Post-transplant]

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

8. Percentage of Participants With GVHD-free Survival [1 Year Post-transplant]

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

9. Percentage of Participants With Overall Survival [1 Year Post-transplant]

10. Percentage of Participants With Neutrophil Recovery [Days 28 and 100 Post-transplant]

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

11. Percentage of Participants With Platelet Recovery [Days 60 and 100 Post-transplant]

    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.

12. Donor Cell Engraftment [Days 28 and 100 Post-transplant]

    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.

13. Primary Cause of Death [1 Year Post-transplant]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: 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:

6. 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.

7. 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.

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

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

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

11. 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.

12. 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).

13. 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.

14. 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.

Contacts and Locations

Locations

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

Sponsors and Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)
• Blood and Marrow Transplant Clinical Trials Network
• National Cancer Institute (NCI)

Investigators

• Study Director: Mary Horowitz, MD, Center for International Blood and Marrow Transplant Research

Study Documents (Full-Text)

• Study Protocol - Jul 17, 2015
• Statistical Analysis Plan - Nov 9, 2016

More Information

Additional Information:

• Blood and Marrow Transplant Clinical Trials Network
• National Marrow Donor Program

Publications

• 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.
• 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. Review.

• Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
• ClinicalTrials.gov Identifier: NCT02208037
• Other Study ID Numbers: BMTCTN1203; U01HL069294
• First Posted: Aug 4, 2014
• Last Update Posted: Jan 23, 2019
• Last Verified: Dec 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by National Heart, Lung, and Blood Institute (NHLBI): Acute Lymphoblastic Leukemia/Lymphoma; Acute Myelogenous Leukemia; Mantel-Cell Lymphoma; Hematopoietic Transplant; GVHD Prophylaxis
• Additional relevant MeSH terms: Lymphoma; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Graft vs Host Disease; Mycophenolic Acid; Maraviroc; Cyclophosphamide; Methotrexate; Bortezomib; Tacrolimus

Study Results

Participant Flow

Arm/Group Title	Tacrolimus/Methotrexate/Bortezomib	Tacrolimus/Methotrexate/Maraviroc	Tacrolimus/MMF/Cyclophosphamide
Arm/Group Description	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.
Period Title: Overall Study
STARTED	93	93	93
COMPLETED	89	92	92
NOT COMPLETED	4	1	1

Baseline Characteristics

Arm/Group Title	Tacrolimus/Methotrexate/Bortezomib	Tacrolimus/Methotrexate/Maraviroc	Tacrolimus/MMF/Cyclophosphamide	Total
Arm/Group Description	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.	Total of all reporting groups
Overall Participants	89	92	92	273
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	64	64	64	64
Sex: Female, Male (Count of Participants)
Female	31 34.8%	37 40.2%	30 32.6%	98 35.9%
Male	58 65.2%	55 59.8%	62 67.4%	175 64.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 1.1%	3 3.3%	7 7.6%	11 4%
Not Hispanic or Latino	85 95.5%	86 93.5%	81 88%	252 92.3%
Unknown or Not Reported	3 3.4%	3 3.3%	4 4.3%	10 3.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	2 2.2%	3 3.3%	1 1.1%	6 2.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	3 3.4%	1 1.1%	3 3.3%	7 2.6%
White	79 88.8%	81 88%	82 89.1%	242 88.6%
More than one race	1 1.1%	0 0%	1 1.1%	2 0.7%
Unknown or Not Reported	4 4.5%	7 7.6%	5 5.4%	16 5.9%
HCT-CI Comorbidity Index (Count of Participants)
0	24 27%	18 19.6%	26 28.3%	68 24.9%
1-2	31 34.8%	37 40.2%	27 29.3%	95 34.8%
3 or greater	34 38.2%	37 40.2%	39 42.4%	110 40.3%
Karnofsky Performance Score (Count of Participants)
100	13 14.6%	10 10.9%	11 12%	34 12.5%
90	39 43.8%	39 42.4%	42 45.7%	120 44%
80	29 32.6%	27 29.3%	28 30.4%	84 30.8%
70	8 9%	16 17.4%	11 12%	35 12.8%
HLA Matching and Donor Type (Count of Participants)
Matched Sibling (6/6)	29 32.6%	33 35.9%	29 31.5%	91 33.3%
Matched Other Relative (6/6)	1 1.1%	1 1.1%	4 4.3%	6 2.2%
Matched Unrelated (8/8)	53 59.6%	48 52.2%	50 54.3%	151 55.3%
Mismatched Unrelated (7/8)	6 6.7%	10 10.9%	9 9.8%	25 9.2%
Primary Diagnosis (Count of Participants)
Acute Myeloid Leukemia (AML)	46 51.7%	49 53.3%	49 53.3%	144 52.7%
Acute Lymphoblastic Leukemia (ALL)	12 13.5%	11 12%	8 8.7%	31 11.4%
Chronic Myelogeneous Leukemia (CML)	2 2.2%	2 2.2%	3 3.3%	7 2.6%
Chronic Lymphocytic Leukemia (CLL)	2 2.2%	3 3.3%	0 0%	5 1.8%
Myelodysplastic Syndrome (MDS)	16 18%	15 16.3%	17 18.5%	48 17.6%
Follicular Lymphoma	3 3.4%	6 6.5%	5 5.4%	14 5.1%
Diffuse Large B-Cell Lymphoma	4 4.5%	1 1.1%	7 7.6%	12 4.4%
Mantle Cell Lymphoma	4 4.5%	4 4.3%	1 1.1%	9 3.3%
Hodgkin's Lymphoma	0 0%	1 1.1%	2 2.2%	3 1.1%
Time from Diagnosis to Transplant (months) [Median (Full Range) ]
Median (Full Range) [months]	7.1	6.3	7.4	7.1
Donor/Recipient Sex Matching (Count of Participants)
Male donor / Male Recipient	44 49.4%	39 42.4%	43 46.7%	126 46.2%
Male donor / Female Recipient	19 21.3%	18 19.6%	20 21.7%	57 20.9%
Female donor / Male Recipient	14 15.7%	16 17.4%	19 20.7%	49 17.9%
Female donor / Female Recipient	12 13.5%	19 20.7%	10 10.9%	41 15%
Donor/Recipient Cytomegalovirus (CMV) Status (Count of Participants)
Donor Positive / Recipient Positive	29 32.6%	28 30.4%	25 27.2%	82 30%
Donor Positive / Recipient Negative	4 4.5%	19 20.7%	7 7.6%	30 11%
Donor Negative / Recipient Positive	25 28.1%	19 20.7%	26 28.3%	70 25.6%
Donor Negative / Recipient Negative	31 34.8%	26 28.3%	34 37%	91 33.3%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With GVHD/Relapse or Progression-free Survival (GRFS)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tacrolimus/Methotrexate/Bortezomib	Tacrolimus/Methotrexate/Maraviroc	Tacrolimus/MMF/Cyclophosphamide
Arm/Group Description	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.
Measure Participants	89	92	92
Number (90% Confidence Interval) [percentage of participants]	35.5 39.9%	27.2 29.6%	44.1 47.9%

2. Secondary Outcome

Title	Percentage of Participants With Grade II-IV Acute GVHD
Description	Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995: Skin stage: 0: No rash Rash <25% of body surface area Rash on 25-50% of body surface area Rash on > 50% of body surface area Generalized erythroderma with bullous formation Liver stage (based on bilirubin level)*: 0: <2 mg/dL 2-3 mg/dL 3.01-6 mg/dL 6.01-15.0 mg/dL >15 mg/dL GI stage*: 0: No diarrhea or diarrhea <500 mL/day Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD Diarrhea 1000-1499 mL/day Diarrhea >1500 mL/day 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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tacrolimus/Methotrexate/Bortezomib	Tacrolimus/Methotrexate/Maraviroc	Tacrolimus/MMF/Cyclophosphamide
Arm/Group Description	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.
Measure Participants	89	92	92
Number (90% Confidence Interval) [percentage of participants]	26 29.2%	32 34.8%	27 29.3%

3. Secondary Outcome

Title	Percentage of Participants With Grade III-IV Acute GVHD
Description	Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995: Skin stage: 0: No rash Rash <25% of body surface area Rash on 25-50% of body surface area Rash on > 50% of body surface area 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 Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD Diarrhea 1000-1499 mL/day Diarrhea >1500 mL/day 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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tacrolimus/Methotrexate/Bortezomib	Tacrolimus/Methotrexate/Maraviroc	Tacrolimus/MMF/Cyclophosphamide
Arm/Group Description	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.
Measure Participants	89	92	92
Number (90% Confidence Interval) [percentage of participants]	8 9%	9 9.8%	2 2.2%

4. Secondary Outcome

Title	Percentage of Participants With Chronic GVHD
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tacrolimus/Methotrexate/Bortezomib	Tacrolimus/Methotrexate/Maraviroc	Tacrolimus/MMF/Cyclophosphamide
Arm/Group Description	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.
Measure Participants	89	92	92
Number (90% Confidence Interval) [percentage of participants]	39 43.8%	43 46.7%	28 30.4%

5. Secondary Outcome

Title	Percentage of Participants With Chronic GVHD Requiring Immunosupressive Therapy
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tacrolimus/Methotrexate/Bortezomib	Tacrolimus/Methotrexate/Maraviroc	Tacrolimus/MMF/Cyclophosphamide
Arm/Group Description	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.
Measure Participants	89	92	92
Number (90% Confidence Interval) [percentage of participants]	29 32.6%	33 35.9%	22 23.9%

6. Secondary Outcome

Title	Percentage of Participants With Disease Relapse or Progression
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tacrolimus/Methotrexate/Bortezomib	Tacrolimus/Methotrexate/Maraviroc	Tacrolimus/MMF/Cyclophosphamide
Arm/Group Description	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.
Measure Participants	89	92	92
Number (90% Confidence Interval) [percentage of participants]	24 27%	31 33.7%	28 30.4%

7. Secondary Outcome

Title	Percentage of Participants With Transplant-Related Mortality (TRM)
Description	TRM is defined as death without prior disease relapse or progression.
Time Frame	1 Year Post-transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tacrolimus/Methotrexate/Bortezomib	Tacrolimus/Methotrexate/Maraviroc	Tacrolimus/MMF/Cyclophosphamide
Arm/Group Description	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.
Measure Participants	89	92	92
Number (90% Confidence Interval) [percentage of participants]	17 19.1%	16 17.4%	11 12%

8. Secondary Outcome

Title	Percentage of Participants With Disease-free Survival
Description	Disease-free survival is defined as being alive and free of disease relapse or progression.
Time Frame	1 Year Post-transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tacrolimus/Methotrexate/Bortezomib	Tacrolimus/Methotrexate/Maraviroc	Tacrolimus/MMF/Cyclophosphamide
Arm/Group Description	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.
Measure Participants	89	92	92
Number (90% Confidence Interval) [percentage of participants]	58 65.2%	56 60.9%	60 65.2%

9. Secondary Outcome

Title	Percentage of Participants With GVHD-free Survival
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tacrolimus/Methotrexate/Bortezomib	Tacrolimus/Methotrexate/Maraviroc	Tacrolimus/MMF/Cyclophosphamide
Arm/Group Description	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.
Measure Participants	89	92	92
Number (90% Confidence Interval) [percentage of participants]	43 48.3%	34 37%	53 57.6%

10. Secondary Outcome

Title	Percentage of Participants With Overall Survival
Time Frame	1 Year Post-transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tacrolimus/Methotrexate/Bortezomib	Tacrolimus/Methotrexate/Maraviroc	Tacrolimus/MMF/Cyclophosphamide
Arm/Group Description	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.
Measure Participants	89	92	92
Number (90% Confidence Interval) [percentage of participants]	68 76.4%	66 71.7%	71 77.2%

11. Secondary Outcome

Title	Percentage of Participants With Neutrophil Recovery
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tacrolimus/Methotrexate/Bortezomib	Tacrolimus/Methotrexate/Maraviroc	Tacrolimus/MMF/Cyclophosphamide
Arm/Group Description	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.
Measure Participants	89	92	92
Day 28	94 105.6%	93 101.1%	95 103.3%
Day 100	96 107.9%	95 103.3%	98 106.5%

12. Secondary Outcome

Title	Percentage of Participants With Platelet Recovery
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tacrolimus/Methotrexate/Bortezomib	Tacrolimus/Methotrexate/Maraviroc	Tacrolimus/MMF/Cyclophosphamide
Arm/Group Description	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.
Measure Participants	89	92	92
Day 60	91 102.2%	92 100%	90 97.8%
Day 100	91 102.2%	92 100%	96 104.3%

13. Secondary Outcome

Title	Donor Cell Engraftment
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tacrolimus/Methotrexate/Bortezomib	Tacrolimus/Methotrexate/Maraviroc	Tacrolimus/MMF/Cyclophosphamide
Arm/Group Description	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.
Measure Participants	89	92	92
Full Chimerism	58 65.2%	56 60.9%	64 69.6%
Mixed Chimerism	11 12.4%	10 10.9%	8 8.7%
Graft Rejection	1 1.1%	1 1.1%	2 2.2%
Dead	2 2.2%	4 4.3%	0 0%
No Assay Performed	17 19.1%	21 22.8%	18 19.6%
Full Chimerism	63 70.8%	56 60.9%	62 67.4%
Mixed Chimerism	14 15.7%	17 18.5%	13 14.1%
Graft Rejection	5 5.6%	3 3.3%	3 3.3%
Dead	4 4.5%	10 10.9%	5 5.4%
No Assay Performed	3 3.4%	6 6.5%	9 9.8%

14. Secondary Outcome

Title	Primary Cause of Death
Time Frame	1 Year Post-transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tacrolimus/Methotrexate/Bortezomib	Tacrolimus/Methotrexate/Maraviroc	Tacrolimus/MMF/Cyclophosphamide
Arm/Group Description	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.
Measure Participants	89	92	92
Recurrence/Persistence	11 12.4%	12 13%	15 16.3%
Acute GVHD	3 3.4%	7 7.6%	2 2.2%
Chronic GVHD	2 2.2%	1 1.1%	1 1.1%
Infection	4 4.5%	7 7.6%	4 4.3%
Organ Failure	2 2.2%	2 2.2%	2 2.2%
Hemorrhage	1 1.1%	0 0%	1 1.1%
Interstitial Pneumonia	1 1.1%	0 0%	1 1.1%
Adult Respiratory Distress Syndrome	2 2.2%	1 1.1%	0 0%
Metastatis Breast Cancer	1 1.1%	0 0%	0 0%
Squamous Cell Carcinoma	1 1.1%	0 0%	0 0%
Toxicity - Not Specified	0 0%	1 1.1%	0 0%
Still Alive	61 68.5%	61 66.3%	66 71.7%

Adverse Events

Time Frame	Up to 1 Year Post-transplant
Arm/Group Title	Tacrolimus/Methotrexate/Bortezomib		Tacrolimus/Methotrexate/Maraviroc		Tacrolimus/MMF/Cyclophosphamide
Arm/Group Description	Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Bortezomib.		Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Methotrexate, and Maraviroc.		Participants will receive a GVHD prophylactic regimen of three agents: Tacrolimus, Mycophenolate Mofetil (MMF), and Cyclophosphamide.
All Cause Mortality
	Tacrolimus/Methotrexate/Bortezomib		Tacrolimus/Methotrexate/Maraviroc		Tacrolimus/MMF/Cyclophosphamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/93 (32.3%)		31/93 (33.3%)		27/93 (29%)
Serious Adverse Events
	Tacrolimus/Methotrexate/Bortezomib		Tacrolimus/Methotrexate/Maraviroc		Tacrolimus/MMF/Cyclophosphamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/93 (22.6%)		14/93 (15.1%)		12/93 (12.9%)
Cardiac disorders
Atrial fibrillation	0/93 (0%)	0	1/93 (1.1%)	1	0/93 (0%)	0
Cardiac Arrest	0/93 (0%)	0	1/93 (1.1%)	1	1/93 (1.1%)	1
Cardiac failure	0/93 (0%)	0	0/93 (0%)	0	1/93 (1.1%)	1
Cardiogenic shock	1/93 (1.1%)	1	0/93 (0%)	0	0/93 (0%)	0
Cardiomyopathy	0/93 (0%)	0	1/93 (1.1%)	1	0/93 (0%)	0
Myocardial ischaemia	1/93 (1.1%)	1	0/93 (0%)	0	0/93 (0%)	0
Pericardial effusion	0/93 (0%)	0	0/93 (0%)	0	1/93 (1.1%)	1
Gastrointestinal disorders
Abdominal pain	1/93 (1.1%)	1	0/93 (0%)	0	0/93 (0%)	0
Ascites	1/93 (1.1%)	1	0/93 (0%)	0	0/93 (0%)	0
Colonic pseudo-obstruction	0/93 (0%)	0	0/93 (0%)	0	1/93 (1.1%)	1
Gastrointestinal haemorrhage	0/93 (0%)	0	0/93 (0%)	0	1/93 (1.1%)	1
Gastrointestinal perforation	0/93 (0%)	0	1/93 (1.1%)	1	0/93 (0%)	0
Ileus	1/93 (1.1%)	1	1/93 (1.1%)	1	0/93 (0%)	0
Intestinal perforation	1/93 (1.1%)	1	1/93 (1.1%)	1	0/93 (0%)	0
General disorders
Death	0/93 (0%)	0	0/93 (0%)	0	1/93 (1.1%)	1
Hepatobiliary disorders
Cholecystitis	0/93 (0%)	0	0/93 (0%)	0	2/93 (2.2%)	2
Infections and infestations
Anorectal cellulitis	0/93 (0%)	0	0/93 (0%)	0	1/93 (1.1%)	1
Appendicitis	0/93 (0%)	0	0/93 (0%)	0	1/93 (1.1%)	1
Pneumonia	1/93 (1.1%)	1	0/93 (0%)	0	1/93 (1.1%)	1
Septic shock	1/93 (1.1%)	1	0/93 (0%)	0	0/93 (0%)	0
Injury, poisoning and procedural complications
Fracture	1/93 (1.1%)	1	0/93 (0%)	0	0/93 (0%)	0
Metabolism and nutrition disorders
Hyponatraemia	1/93 (1.1%)	1	0/93 (0%)	0	0/93 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	2/93 (2.2%)	2	0/93 (0%)	0	0/93 (0%)	0
Arthritis	1/93 (1.1%)	1	0/93 (0%)	0	0/93 (0%)	0
Vertebral foraminal stenosis	1/93 (1.1%)	1	0/93 (0%)	0	0/93 (0%)	0
Nervous system disorders
Encephalopathy	1/93 (1.1%)	1	1/93 (1.1%)	1	0/93 (0%)	0
Guillain-Barre syndrome	0/93 (0%)	0	1/93 (1.1%)	1	0/93 (0%)	0
Haemorrhage intracranial	1/93 (1.1%)	1	0/93 (0%)	0	1/93 (1.1%)	1
Syncope	1/93 (1.1%)	1	0/93 (0%)	0	0/93 (0%)	0
Psychiatric disorders
Delirium	0/93 (0%)	0	1/93 (1.1%)	1	0/93 (0%)	0
Mental status changes	0/93 (0%)	0	1/93 (1.1%)	1	0/93 (0%)	0
Renal and urinary disorders
Acute kidney injury	1/93 (1.1%)	1	0/93 (0%)	0	0/93 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/93 (1.1%)	1	0/93 (0%)	0	0/93 (0%)	0
Pulmonary embolism	0/93 (0%)	0	1/93 (1.1%)	1	0/93 (0%)	0
Respiratory failure	1/93 (1.1%)	1	2/93 (2.2%)	2	0/93 (0%)	0
Vascular disorders
Embolism	0/93 (0%)	0	1/93 (1.1%)	1	0/93 (0%)	0
Hypotension	1/93 (1.1%)	1	0/93 (0%)	0	0/93 (0%)	0
Other (Not Including Serious) Adverse Events
	Tacrolimus/Methotrexate/Bortezomib		Tacrolimus/Methotrexate/Maraviroc		Tacrolimus/MMF/Cyclophosphamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/93 (0%)		0/93 (0%)		0/93 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.