Vorinostat Plus Tacrolimus & Methotrexate to Prevent Graft vs Host Disease Following Unrelated Stem Cell Transplant

NCT01790568 | Completed Phase 2 Results DMC

• 2 other identifiers: UMCC 2012.047HUM00070080
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This protocol, UMCC 2012.047, was a pilot study initially intended for 12 subjects. After completing enrollment of the planned 12 subjects, we are extending the study to an additional 25 subjects. The trial will examine the safety and efficacy of the addition of vorinostat, the study drug, to standard medications to try to prevent or lower the risk of graft versus-host disease (GVHD) for recipients of unrelated (matched) donor, blood or marrow stem cell transplants. The transplant regimens, chosen according to current institutional policy, will depend upon the recipients underlying disease (their blood cancer or other blood disorder), previous therapy, and current health issues. GVHD prophylaxis (preventive drug intervention) will be the local institutional standard for post-transplant immunosuppression, including tacrolimus and methotrexate, plus vorinostat. Vorinostat will be given twice daily orally beginning 10 days prior to the recipient's transplant and continue for up to 100 days after transplant.

Conditions

Graft vs Host Disease; Hematologic Neoplasms; Non-Neoplastic Hematologic and Lymphocytic Disorder

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients That Experience Grade 2-4 GVHD Within 100 Days of Transplant

  GVHD Staging: Grade 2: (Skin) Maculopapular rash 25-50% BSA, (Liver) bilirubin 3.1-6mg/dl, (Gut) 1000-1500 ml/day for adult and 20-30ml/kg/day for child. Grade 3: (Skin) Maculopapular rash \>50% BSA, (Liver) 6.1-15mg/dl, (Gut) \>1500mg/day for adult and \>30ml/kg/day for child. Grade 4: (Skin) Generalized erythroderma plus bullous formation and desquamation \>5% BSA, (Liver) \>15mg/dl, (Gut) Severe abdominal pain with or without ileus, or grossly bloody stool.

  100 Days

Secondary Outcomes (2)

• Percentage of Patients Alive at 1 Year

  1 Year

• Non-Relapse Mortality Incidence

  1 year

Study Arms (1)

Vorinostat

EXPERIMENTAL

Vorinostat, in combination with standard of care medications tacrolimus and methotrexate, for GVHD prophylaxis after unrelated donor stem cell transplant.

Drug: Vorinostat; Drug: Tacrolimus; Drug: Methotrexate

Interventions

Vorinostat DRUG

administered at a dose of 100 mg orally, twice daily starting on day -10 in order to achieve steady-state prior to beginning the conditioning chemotherapy, and continued after transplant (day 0) until day +100.

Also known as: Zolinza

Vorinostat

Tacrolimus DRUG

Vorinostat

Methotrexate DRUG

Vorinostat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 CNS involvement is eligible if CNS disease is in remission at time of study consideration.
• Age between 18-75 years
• The donor and recipient must have an HLA-8/8 allelic match at the HLA-A, -B, -C, and -DRB1.
• Diagnosis of following diseases (subject to additional complex screening criteria)
• Acute Myelogenous Leukemia:
• First remission (cytogenetic intermediate or high risk)
• Second or subsequent remission
• Chronic Myelogenous Leukemia:
• First, subsequent chronic phases, or atypical
• Accelerated Phase
• Myelodysplastic syndromes
• Chronic Lymphocytic Leukemia
• Primary Myelofibrosis
• Mature B Cell Malignancies (including Mantle Cell Lymphoma, Follicular Lymphoma. Diffuse Large B Cell Lymphoma, Non-Hodgkin Lymphoma not otherwise specified)
• Karnofsky (Attempt to classify a cancer patients' activities of daily life that runs from 0 to 100 where 100 represents perfect health and 0 represents death) \>70%

You may not qualify if:

• Not a candidate for an unrelated donor allogeneic transplant conditioning regimen based on the current institutional 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
• Undergoing a total body irradiation (TBI)-based conditioning regimen (TBI 1200 cGy)
• Uncontrolled 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 PI
• Any medical or psychological comorbidities/conditions that would keep the patient from complying with the needs of the protocol and/or would markedly increase the risk of morbidity and mortality.
• Pregnant women or nursing mothers.
• Evidence of HIV seropositivity and/or positive PCR assay, HTLV1 / HTLV2 seropositivity.
• Evidence of Hepatitis B or Hepatitis C PCR positivity.
• Less than 18 years of age.
• A history of prolonged QTc syndrome.
• Taking or have had prior treatment with a drug like vorinostat within the last 30 days.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (1)

University of Michigan Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (1)

• Choi SW, Braun T, Henig I, Gatza E, Magenau J, Parkin B, Pawarode A, Riwes M, Yanik G, Dinarello CA, Reddy P. Vorinostat plus tacrolimus/methotrexate to prevent GVHD after myeloablative conditioning, unrelated donor HCT. Blood. 2017 Oct 12;130(15):1760-1767. doi: 10.1182/blood-2017-06-790469. Epub 2017 Aug 7.

  PMID: 28784598 BACKGROUND

MeSH Terms

Conditions

Graft vs Host Disease; Hematologic Neoplasms

Interventions

Vorinostat; Tacrolimus; Methotrexate

Condition Hierarchy (Ancestors)

Immune System Diseases; Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Macrolides; Lactones; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Pavan Reddy, M.D.
• Organization: University of Michigan Comprehensive Cancer Center

reddypr@umich.edu

734-936-8785

Study Officials

• Pavan Reddy, MD

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2012
• First Posted: February 13, 2013
• Study Start: December 1, 2014
• Primary Completion: January 1, 2017
• Study Completion: October 31, 2017
• Last Updated: August 13, 2018
• Results First Posted: January 2, 2018

Record last verified: 2018-07

Locations

US (1)