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Vorinostat, Tacrolimus, and Methotrexate in Preventing GVHD After Stem Cell Transplant in Patients With Hematological Malignancies

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT01789255
Collaborator
(none)
12
Enrollment
1
Location
1
Arm
9
Duration (Months)
1.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This pilot phase II trial studies how well giving vorinostat, tacrolimus, and methotrexate works in preventing graft-versus-host disease (GVHD) after stem cell transplant in patients with hematological malignancies. Vorinostat, tacrolimus, and methotrexate may be an effective treatment for GVHD caused by a bone marrow transplant.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. To assess the safety and the feasibility of the addition of vorinostat to tacrolimus and methotrexate GVHD prophylaxis.
SECONDARY OBJECTIVES:
  1. To determine day 100 grades 2-4 acute GVHD. II. To determine 1-year overall survival and relapse-free survival. III. To correlate plasma concentrations of inflammatory markers of acute GVHD. IV. To correlate protein acetylation in peripheral blood mononuclear cells before and after administration of vorinostat.
OUTLINE:

Patients receive vorinostat orally (PO) twice daily (BID) on days -10 to 100. Beginning on day -3, patients receive tacrolimus intravenously (IV) continuously or PO BID (or cyclosporine IV continuously or PO in patients unable to tolerate tacrolimus) with taper on days 100-180.Patients also receive methotrexate IV once daily (QD) on days 1, 3, 6, and 11.

After completion of study treatment, patients are followed up periodically for 1 year.

Study Design

Study Type:
Interventional
Actual Enrollment :
12 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Supportive Care
Official Title:
A Pilot Trial of Vorinostat Plus Tacrolimus and Methotrexate to Prevent Graft Versus Host Disease Following Unrelated Donor Hematopoietic Stem Cell Transplantation
Study Start Date :
Jun 1, 2013
Actual Primary Completion Date :
Mar 1, 2014
Actual Study Completion Date :
Mar 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: Supportive care (vorinostat, tacrolimus, methotrexate)

Patients receive vorinostat PO BID on days -10 to 100. Beginning on day -3, patients receive tacrolimus IV continuously or PO BID (or cyclosporine IV continuously or PO in patients unable to tolerate tacrolimus) with taper on days 100-180.Patients also receive methotrexate IV QD on days 1, 3, 6, and 11.

Drug: vorinostat
Given PO
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza

    • Drug: tacrolimus
    Given IV or PO
    Other Names:
  • FK 506
  • Prograf

    • Drug: cyclosporine
    Given IV or PO
    Other Names:
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune

    • Drug: methotrexate
    Given IV
    Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX

    • Other: laboratory biomarker analysis
    Correlative studies

    Other: pharmacological study
    Correlative studies
    Other Names:
  • pharmacological studies

    		•

    Outcome Measures

    Primary Outcome Measures

    1. The Number of Participants That Experience Grade 2-4 Acute GVHD (Graft Versus Host Disease) by Day 100 [Day 100]

      The incidence of grade 2-4 acute GVHD (Graft Versus Host Disease) by day 100 Grade 2 GVHD: Maculopapular rash covering 25-50% of BSA (Body Surface Area), bilirubin between 3.1-6 mg/dl, and/ or adult stool output between 1000-1500 ml/day (child between 20-30 ml/kg/day). Grade 3 GVHD: Maculopapular rash covering >50% of BSA, bilirubin between 6.1-15 mg/dl, and/ or adult stool output >1500 ml/day (child >30 ml/kg/day). Grade 4 GVHD: Generalized erythroderma plus bullous formation and desquamation >5% BSA, bilirubin >15 mg/dl, and/ or severe abdominal pain with or without ileus, or grossly bloody stool.

    Secondary Outcome Measures

    1. Mean Percent of Planned Dose Administered [Up to day 30]

      The addition of vorinostat to tacrolimus and methotrexate for GVHD prophylaxis will be considered feasible if 60% or more of the planned doses are administered.

    2. The Percentage of Patients Alive Without GVHD or Use of Steroids [Up to 1 year]

      The percentage of patients alive without GVHD or use of steroids at 1 year.

    3. The Percentage of Patients Alive at 1 Year [Up to 1 year]

      The percentage of patients alive at 1 year

    4. The Percentage of Patients With Relapse at 1 Year [Up to 1 year]

    5. Median Ac-H3 Levels in Patients Treated With Vorinostat and Patients Not Treated With Vorinostat [Up to day 100]

      Median Ac-H3 levels ( depicted as a ratio of ac-H2 optical density (OD) and beta actin OD) were compared in patients treated with Vorinostat to patients not treated with Vorinostat. Optical Density is a dimensionless unit.

    6. Median Plasma Concentration of IL-6 in Patients Treated With Vorinostat and Patients Not Treated With Vorinostat [Up to day 100]

      Median plasma concentration of IL-6 (Interleukin-6 cytokine) was compared in patients treated with Vorinostat to those not treated with Vorinostat.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • A prospective patient for allogeneic HSCT for hematologic conditions, both malignant and non-malignant; donor can be unrelated marrow or peripheral blood cells; a patient with history of central nervous system (CNS) involvement is eligible if CNS disease is in remission at time of study consideration

    • The donor and recipient must have a human leukocyte antigen (HLA)-8/8 allelic match at the HLA-A, -B, -C, and -DRB1; high-resolution typing is required for all alleles

    • Diagnoses to be included:

    • Acute myelogenous leukemia at the following stages:

    • First remission

    • Second or subsequent remission

    • Complete remission is defined as the absence of blasts in the peripheral circulation at the time of enrollment and < 5% blasts in the bone marrow

    • Chronic myelogenous leukemia at the following stages:

    • First or subsequent chronic phase:

    • Patient refused tyrosine kinase therapy or is otherwise not suited for it

    • Stable, not hematologic remission: blasts present in marrow and/or peripheral blood, but disease does not qualify as accelerated or blast phase

    • Hematologic remission: no blast cells or precursor cells in the blood or marrow

    • Partial cytogenetic remission: Philadelphia chromosome positive (Ph+) metaphases > 0% but < 35%

    • Complete cytogenetic remission: absence of Ph+ metaphases

    • Accelerated phase - any one of the following symptoms:

    • White blood cells (WBC) difficult to control (> 50 x 10^9/L despite therapy)

    • Rapid doubling of WBC (< 5 days)

    • 10% blasts in blood or marrow

    • 20% blasts and/or promyelocytes in blood or marrow

    • 20% basophils and/or eosinophils in blood

    • Anemia or thrombocytopenia unresponsive to standard treatment

    • Persistent thrombocytosis (> 1000 x 10^9/L)

    • Cytogenetic abnormalities in addition to Ph+

    • Increasing splenomegaly

    • Marrow fibrosis

    • Myelodysplastic syndromes at any of the following stages:

    • Refractory anemia

    • Refractory anemia with ringed sideroblasts

    • Refractory cytopenia with multilineage dysplasia

    • Refractory cytopenia with multilineage dysplasia and ringed sideroblasts

    • Refractory anemia with excess blasts-1 (5-10% blasts)

    • Refractory anemia with excess blasts-2 (10-20% blasts)

    • Myelodysplastic syndrome, unclassified

    • Myelodysplastic syndrome (MDS) associated with isolated del (5q)

    • Chronic myelomonocytic leukemia

    • Primary Myelofibrosis

    • Intermediate-2 risk or high risk disease

    • Patients should have extinguished standard of care options prior to being considered for this trial

    • Chronic lymphocytic leukemia

    • Complete remission: the disease is completely absent and no relapse occurred prior to the preparative regimen; requires all of the following:

    • Nodular partial remission: complete response with persistent lymphoid nodules in bone marrow

    • Partial remission: reduction of more than 50% in the disease burden regardless of the number of lines of therapy received

    • Mature B cell malignancies

    • Patients should have extinguished standard of care options prior to being considered eligible for this trial

    • First complete remission (CR1) confirmed: complete disappearance of all known disease; the term "confirmed" is defined as a laboratory and/or pathological or radiographic determination.

    • CR1 unconfirmed (CRU1): complete disappearance of all known disease with the exception of persistent scan abnormalities of unknown significance; the term "unconfirmed" is defined as scan abnormalities of unknown significance that are not biopsied or otherwise evaluated

    • Second or subsequent complete remission (CR2+) confirmed: the recipient relapsed, then achieved complete absence of disease without radiographic evidence of disease

    • CR2+ unconfirmed: the recipient has achieved a second or subsequent complete response but has persistent radiographic abnormalities of unknown significance.

    • Partial remission: reductions of >= 50% in greatest diameter of all sites of known disease and no new sites

    • Karnofsky >= 70%

    • Life expectancy of greater than 6 months

    • Total bilirubin =< 2.5 mg% (unless from Gilbert's disease or disease-related)

    • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 3.0 X institutional upper limit of normal

    • Estimated or actual glomerular filtration rate (GFR) > 50 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal; GFR should be corrected for body surface area (BSA)

    • Diffusing capacity of the lung for carbon monoxide (DLCO) > 50%; DLCO should be corrected for hemoglobin

    • Forced expiratory volume in 1 second (FEV1) > 50%

    • Forced vital capacity (FVC) > 50%

    • Ejection fraction >= 50%

    • The effects of vorinostat on the developing human fetus are unknown; for this reason and because histone deacetylase inhibitor agents as well as other therapeutic agents used in this trial (e.g., tacrolimus and methotrexate) are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of vorinostat administration

    • Ability to understand and the willingness to sign a written informed consent document

    • Patients must be able to swallow capsules/tablets

    Exclusion Criteria:

    • Patients who are not a candidate for an unrelated donor allogeneic HSCT based on the current institutional bone marrow transplant (BMT) program clinical practice guidelines; organ function criteria will be utilized per the current institutional BMT program clinical practice guidelines; there will be no restriction to study entry based on hematological parameters

    • History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat

    • Patients undergoing a total body irradiation (TBI)-based conditioning regimen (TBI 1200 centigray [cGy])

    • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements; patients still under therapy for presumed or proven infection are eligible provided there is clear evidence (radiographic findings and/or culture results) that the infection is well-controlled; patients under treatment for infection will be enrolled only after clearance from the Principal Investigator (PI)

    • Pregnant women are excluded from this study because vorinostat is a histone deacetylase inhibitor agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with vorinostat, breastfeeding should be discontinued if the mother is treated with vorinostat

    • Patients with evidence of human immunodeficiency virus (HIV) seropositivity and/or positive polymerase chain reaction (PCR) assay, human T-lymphotropic virus (HTLV)1/HTLV2 seropositivity; the safety of allogeneic HSCT is not yet well-established for this population

    • Patients with evidence of hepatitis B or hepatitis C PCR positivity; hepatitis reactivation following myelosuppressive therapy can lead to fatal complications

    • Patients with a history of prolonged corrected QT interval (QTc) syndrome

    • Patients asking or who have had prior treatment with a drug like vorinostat (i.e., valproic acid) within the last 30 days

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Michigan University Hospital Ann Arbor Michigan United States 48109

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Pavan Reddy, University of Michigan University Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01789255
    Other Study ID Numbers:
    • NCI-2013-00355
    • NCI-2013-00355
    • HUM00070080
    • UMCC 2012.047
    • 9330
    • P30CA046592
    First Posted:
    Feb 12, 2013
    Last Update Posted:
    Jul 24, 2018
    Last Verified:
    Jun 1, 2018
    Additional relevant MeSH terms:
    Burkitt Lymphoma
    Lymphoma
    Leukemia
    Leukemia, Myeloid
    Leukemia, Myeloid, Acute
    Lymphoma, Follicular
    Lymphoma, Non-Hodgkin
    Neoplasm Metastasis
    Leukemia, Lymphoid
    Lymphoma, B-Cell
    Leukemia, Lymphocytic, Chronic, B-Cell
    Hodgkin Disease
    Lymphoma, Mantle-Cell
    Leukemia, Myelogenous, Chronic, BCR-ABL Positive
    Lymphoma, B-Cell, Marginal Zone
    Precursor Cell Lymphoblastic Leukemia-Lymphoma
    Lymphoma, Large B-Cell, Diffuse
    Lymphoma, Large-Cell, Immunoblastic
    Plasmablastic Lymphoma
    Waldenstrom Macroglobulinemia
    Leukemia, Myelomonocytic, Chronic
    Leukemia, Myelomonocytic, Juvenile
    Leukemia, Hairy Cell
    Leukemia, Myeloid, Chronic-Phase
    Lymphomatoid Granulomatosis
    Leukemia, Myeloid, Accelerated Phase
    Lymphoma, Extranodal NK-T-Cell
    Intraocular Lymphoma
    Anemia
    Myelodysplastic Syndromes
    Myeloproliferative Disorders
    Anemia, Refractory
    Lymphoproliferative Disorders
    Myelodysplastic-Myeloproliferative Diseases
    Anemia, Refractory, with Excess of Blasts
    Graft vs Host Disease
    Recurrence
    Cyclosporine
    Methotrexate
    Vorinostat
    Tacrolimus
    Cyclosporins

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Supportive Care (Vorinostat, Tacrolimus, Methotrexate)
    Arm/Group Description Patients receive vorinostat PO BID on days -10 to 100. Beginning on day -3, patients receive tacrolimus IV continuously or PO BID (or cyclosporine IV continuously or PO in patients unable to tolerate tacrolimus) with taper on days 100-180. Patients also receive methotrexate IV QD on days 1, 3, 6, and 11.
    Period Title: Overall Study
    STARTED 12
    COMPLETED 12
    NOT COMPLETED 0

    Baseline Characteristics

    Arm/Group Title Supportive Care (Vorinostat, Tacrolimus, Methotrexate)
    Arm/Group Description Patients receive vorinostat PO BID on days -10 to 100. Beginning on day -3, patients receive tacrolimus IV continuously or PO BID (or cyclosporine IV continuously or PO in patients unable to tolerate tacrolimus) with taper on days 100-180. Patients also receive methotrexate IV QD on days 1, 3, 6, and 11.
    Overall Participants 12
    Age (years) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [years]
    49
    Sex: Female, Male (Count of Participants)
    Female
    7
    58.3%
    Male
    5
    41.7%

    Outcome Measures

    1. Primary Outcome
    Title The Number of Participants That Experience Grade 2-4 Acute GVHD (Graft Versus Host Disease) by Day 100
    Description The incidence of grade 2-4 acute GVHD (Graft Versus Host Disease) by day 100 Grade 2 GVHD: Maculopapular rash covering 25-50% of BSA (Body Surface Area), bilirubin between 3.1-6 mg/dl, and/ or adult stool output between 1000-1500 ml/day (child between 20-30 ml/kg/day). Grade 3 GVHD: Maculopapular rash covering >50% of BSA, bilirubin between 6.1-15 mg/dl, and/ or adult stool output >1500 ml/day (child >30 ml/kg/day). Grade 4 GVHD: Generalized erythroderma plus bullous formation and desquamation >5% BSA, bilirubin >15 mg/dl, and/ or severe abdominal pain with or without ileus, or grossly bloody stool.
    Time Frame Day 100

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Supportive Care (Vorinostat, Tacrolimus, Methotrexate)
    Arm/Group Description Patients receive vorinostat PO BID on days -10 to 100. Beginning on day -3, patients receive tacrolimus IV continuously or PO BID (or cyclosporine IV continuously or PO in patients unable to tolerate tacrolimus) with taper on days 100-180. Patients also receive methotrexate IV QD on days 1, 3, 6, and 11.
    Measure Participants 12
    Number [participants]
    2
    16.7%
    2. Secondary Outcome
    Title Mean Percent of Planned Dose Administered
    Description The addition of vorinostat to tacrolimus and methotrexate for GVHD prophylaxis will be considered feasible if 60% or more of the planned doses are administered.
    Time Frame Up to day 30

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Supportive Care (Vorinostat, Tacrolimus, Methotrexate)
    Arm/Group Description Patients receive vorinostat PO BID on days -10 to 100. Beginning on day -3, patients receive tacrolimus IV continuously or PO BID (or cyclosporine IV continuously or PO in patients unable to tolerate tacrolimus) with taper on days 100-180. Patients also receive methotrexate IV QD on days 1, 3, 6, and 11.
    Measure Participants 12
    Mean (Full Range) [percent of dose administered]
    82.5
    3. Secondary Outcome
    Title The Percentage of Patients Alive Without GVHD or Use of Steroids
    Description The percentage of patients alive without GVHD or use of steroids at 1 year.
    Time Frame Up to 1 year

    Outcome Measure Data

    Analysis Population Description
    This trial consisted of an initial pilot phase, funded by the NCI, that enrolled 12 patients (NCT01789255). The trial was extended to enroll an additional 25 patients. The results presented here include information for all 37 patients. The analysis population description for all 37 patients can be found under NCT01790568.
    Arm/Group Title Supportive Care (Vorinostat, Tacrolimus, Methotrexate)
    Arm/Group Description Patients receive vorinostat PO BID on days -10 to 100. Beginning on day -3, patients receive tacrolimus IV continuously or PO BID (or cyclosporine IV continuously or PO in patients unable to tolerate tacrolimus) with taper on days 100-180. Patients also receive methotrexate IV QD on days 1, 3, 6, and 11.
    Measure Participants 37
    Number [percentage of patients]
    47
    4. Secondary Outcome
    Title The Percentage of Patients Alive at 1 Year
    Description The percentage of patients alive at 1 year
    Time Frame Up to 1 year

    Outcome Measure Data

    Analysis Population Description
    This trial consisted of an initial pilot phase, funded by the NCI, that enrolled 12 patients (NCT01789255). The trial was extended to enroll an additional 25 patients. The results presented here include information for all 37 patients. The analysis population description for all 37 patients can be found under NCT01790568.
    Arm/Group Title Supportive Care (Vorinostat, Tacrolimus, Methotrexate)
    Arm/Group Description Patients receive vorinostat PO BID on days -10 to 100. Beginning on day -3, patients receive tacrolimus IV continuously or PO BID (or cyclosporine IV continuously or PO in patients unable to tolerate tacrolimus) with taper on days 100-180. Patients also receive methotrexate IV QD on days 1, 3, 6, and 11.
    Measure Participants 37
    Number [percentage of patients]
    76
    5. Secondary Outcome
    Title The Percentage of Patients With Relapse at 1 Year
    Description
    Time Frame Up to 1 year

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Supportive Care (Vorinostat, Tacrolimus, Methotrexate)
    Arm/Group Description Patients receive vorinostat PO BID on days -10 to 100. Beginning on day -3, patients receive tacrolimus IV continuously or PO BID (or cyclosporine IV continuously or PO in patients unable to tolerate tacrolimus) with taper on days 100-180. Patients also receive methotrexate IV QD on days 1, 3, 6, and 11.
    Measure Participants 12
    Number [percentage of patients]
    19
    6. Secondary Outcome
    Title Median Ac-H3 Levels in Patients Treated With Vorinostat and Patients Not Treated With Vorinostat
    Description Median Ac-H3 levels ( depicted as a ratio of ac-H2 optical density (OD) and beta actin OD) were compared in patients treated with Vorinostat to patients not treated with Vorinostat. Optical Density is a dimensionless unit.
    Time Frame Up to day 100

    Outcome Measure Data

    Analysis Population Description
    This trial consisted of an initial pilot phase, funded by the NCI, that enrolled 12 patients (NCT01789255). The trial was extended to enroll an additional 25 patients. The results presented here include information for all 37 patients. The analysis population description for all 37 patients can be found under NCT01790568.
    Arm/Group Title Supportive Care (Vorinostat, Tacrolimus, Methotrexate)
    Arm/Group Description Patients receive vorinostat PO BID on days -10 to 100. Beginning on day -3, patients receive tacrolimus IV continuously or PO BID (or cyclosporine IV continuously or PO in patients unable to tolerate tacrolimus) with taper on days 100-180. Patients also receive methotrexate IV QD on days 1, 3, 6, and 11.
    Measure Participants 37
    Treated with Vorinostat
    0.943
    Not Treated with Vorinostat
    0.679
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Supportive Care (Vorinostat, Tacrolimus, Methotrexate)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.02642
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments
    7. Secondary Outcome
    Title Median Plasma Concentration of IL-6 in Patients Treated With Vorinostat and Patients Not Treated With Vorinostat
    Description Median plasma concentration of IL-6 (Interleukin-6 cytokine) was compared in patients treated with Vorinostat to those not treated with Vorinostat.
    Time Frame Up to day 100

    Outcome Measure Data

    Analysis Population Description
    This trial consisted of an initial pilot phase, funded by the NCI, that enrolled 12 patients (NCT01789255). The trial was extended to enroll an additional 25 patients. The results presented here include information for all 37 patients. The analysis population description for all 37 patients can be found under NCT01790568.
    Arm/Group Title Supportive Care (Vorinostat, Tacrolimus, Methotrexate)
    Arm/Group Description Patients receive vorinostat PO BID on days -10 to 100. Beginning on day -3, patients receive tacrolimus IV continuously or PO BID (or cyclosporine IV continuously or PO in patients unable to tolerate tacrolimus) with taper on days 100-180. Patients also receive methotrexate IV QD on days 1, 3, 6, and 11.
    Measure Participants 37
    Treated with Vorinostat
    4.2
    Not Treated with Vorinostat
    7.6
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Supportive Care (Vorinostat, Tacrolimus, Methotrexate)
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.028
    Comments
    Method Wilcoxon (Mann-Whitney)
    Comments

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Supportive Care (Vorinostat, Tacrolimus, Methotrexate)
    Arm/Group Description Patients receive vorinostat PO BID on days -10 to 100. Beginning on day -3, patients receive tacrolimus IV continuously or PO BID (or cyclosporine IV continuously or PO in patients unable to tolerate tacrolimus) with taper on days 100-180. Patients also receive methotrexate IV QD on days 1, 3, 6, and 11.
    All Cause Mortality
    Supportive Care (Vorinostat, Tacrolimus, Methotrexate)
    Affected / at Risk (%) # Events
    Total / (NaN)
    Serious Adverse Events
    Supportive Care (Vorinostat, Tacrolimus, Methotrexate)
    Affected / at Risk (%) # Events
    Total 7/12 (58.3%)
    Blood and lymphatic system disorders
    Anemia 1/12 (8.3%) 1
    Gastrointestinal disorders
    Diarrhea 3/12 (25%) 3
    Dysphagia 1/12 (8.3%) 1
    Nausea 1/12 (8.3%) 1
    Vomiting 1/12 (8.3%) 1
    General disorders
    Non-cardiac chest pain 2/12 (16.7%) 2
    Immune system disorders
    Immune system disorders, Other 1/12 (8.3%) 1
    Infections and infestations
    Abdominal infection 1/12 (8.3%) 1
    Catheter related infection 1/12 (8.3%) 1
    Urinary tract infection 1/12 (8.3%) 1
    Metabolism and nutrition disorders
    Dehydration 1/12 (8.3%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified, Other 3/12 (25%) 3
    Respiratory, thoracic and mediastinal disorders
    Hypoxia 1/12 (8.3%) 1
    Other (Not Including Serious) Adverse Events
    Supportive Care (Vorinostat, Tacrolimus, Methotrexate)
    Affected / at Risk (%) # Events
    Total 10/12 (83.3%)
    Blood and lymphatic system disorders
    Anemia 2/12 (16.7%) 2
    Gastrointestinal disorders
    Diarrhea 4/12 (33.3%) 4
    Dysphagia 1/12 (8.3%) 1
    Mucositis oral 3/12 (25%) 3
    Nausea 3/12 (25%) 5
    Vomiting 3/12 (25%) 4
    General disorders
    Non-cardiac chest pain 2/12 (16.7%) 2
    Pain 1/12 (8.3%) 1
    Immune system disorders
    Immune system disorders, Other 1/12 (8.3%) 1
    Infections and infestations
    Abdominal infection 1/12 (8.3%) 1
    Catheter related infection 1/12 (8.3%) 1
    Urinary tract infection 1/12 (8.3%) 1
    Investigations
    Alanine aminotransferase increased 1/12 (8.3%) 1
    Blood bilirubin increased 2/12 (16.7%) 3
    Creatinine increased 4/12 (33.3%) 5
    Lymphocyte count decreased 1/12 (8.3%) 1
    Neutrophil count decreased 1/12 (8.3%) 1
    Platelet count decreased 8/12 (66.7%) 8
    White blood cell decreased 2/12 (16.7%) 2
    Metabolism and nutrition disorders
    Dehydration 1/12 (8.3%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified, Other 3/12 (25%) 3
    Renal and urinary disorders
    Acute kidney injury 1/12 (8.3%) 1
    Respiratory, thoracic and mediastinal disorders
    Hypoxia 1/12 (8.3%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Pavan Reddy, M.D.
    Organization University of Michigan Comprehensive Cancer Center
    Phone 734-647-5954
    Email reddypr@umich.edu
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01789255
    Other Study ID Numbers:
    • NCI-2013-00355
    • NCI-2013-00355
    • HUM00070080
    • UMCC 2012.047
    • 9330
    • P30CA046592
    First Posted:
    Feb 12, 2013
    Last Update Posted:
    Jul 24, 2018
    Last Verified:
    Jun 1, 2018