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Graft vs Host DiseasePhase 2NCT01790568

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

A Phase 2 study testing Vorinostat, Tacrolimus and Methotrexate in people with Graft vs Host Disease and Hematologic Neoplasms, run by University of Michigan Rogel Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Vorinostat, Tacrolimus and Methotrexate
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
1 siteUnited States
Study dates
Dec 2014to 31 Oct 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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%
  • Life expectancy of greater than 6 months.
  • Organ and marrow function as defined by the institutional BMT (Bone Marrow Transplant) program clinical practice guidelines
  • 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.
  • Able to swallow capsules/tablets

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Michigan Cancer Center

    Ann Arbor, Michigan, 48109

Other trials in United States

About this study

Official title: Pilot Trial of Vorinostat Plus Tacrolimus & Methotrexate to Prevent Graft Versus Host Disease Following Unrelated Donor Allogeneic Transplant

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.

Read the detailed description

This trial is investigating the use of vorinostat (Merck) for standard graft versus-host disease (GVHD) prophylaxis after unrelated donor allogeneic hematopoietic cell transplantation (HCT). A major limitation of the increased utilization of allogeneic HCT (Hematopoietic Cell Transplantation) is the inferior outcomes when donors other than HLA (HumanLeukocyte Antigen)-matched siblings are used. Compared to matched related donors, recipients of matched unrelated donor transplants are at a significantly increased risk of death and transplant-related mortality (TRM). Acute GVHD remains a significant contributor to TRM, which develops in approximately 50-70% of recipients receiving these type of grafts despite standard immunosuppressive prophylaxis. Thus, novel GVHD prophylaxis strategies which successfully attenuate acute GVHD-related complications without increasing other causes of TRM or relapse are needed.

The historical experience of day 100 grade 2-4 acute GVHD in 154 comparable patients treated at the University of Michigan (2005 - 2011) receiving standard GVHD prophylaxis after unrelated donor allogeneic transplant is 48%. At Washington University, the cumulative incidence of acute grade 2-4 GVHD in patients following unrelated donor transplant is 62%.

Research data collectively suggests, that reducing lethal acute GVHD should improve long-term survival for patients undergoing unrelated donor transplant.

Medical subject headings
Graft vs Host Disease, Hematologic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VorinostatDrug

    Also called Zolinza

    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.

  • TacrolimusDrug

  • MethotrexateDrug

Study groups in NCT01790568
Study groupRoleWhat they receive
VorinostatExperimentalVorinostat, in combination with standard of care medications tacrolimus and methotrexate, for GVHD prophylaxis after unrelated donor stem cell transplant.
Receives: Drug: Vorinostat; Drug: Tacrolimus; Drug: Methotrexate

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 100 Days

Secondary outcomes (2)

  1. Percentage of Patients Alive at 1 Year

    Overall survival at 1 Year.

    Measured: 1 Year

  2. Non-Relapse Mortality Incidence

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Feb 2013 (estimated)
  2. Study startDec 2014
  3. Primary completion1 Jan 2017
  4. Study completion31 Oct 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01790568
Sponsor's protocol ID
UMCC 2012.047
Other IDs
HUM00070080
Status last verified
Jul 2018
First submitted
2 Oct 2012
Last updated
13 Aug 2018
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 28784598

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Vorinostat, Tacrolimus and Methotrexate in people with Graft vs Host Disease and Hematologic Neoplasms, run by University of Michigan Rogel Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Patients That Experience Grade 2-4 GVHD Within 100 Days of Transplant (time frame: 100 Days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01790568, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2018.

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