- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT01790568
Vorinostat Plus Tacrolimus & Methotrexate to Prevent Graft vs Host Disease Following Unrelated Stem Cell Transplant
Pilot Trial of Vorinostat Plus Tacrolimus & Methotrexate to Prevent Graft Versus Host Disease Following Unrelated Donor Allogeneic Transplant
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
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.
Studietype
Registrering (Faktiske)
Fase
- Fase 2
Kontakter og plasseringer
Studiesteder
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Michigan
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Ann Arbor, Michigan, Forente stater, 48109
- University of Michigan Cancer Center
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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 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%
- 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
Exclusion Criteria:
- 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.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Forebygging
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
---|---|
Eksperimentell: Vorinostat
Vorinostat, in combination with standard of care medications tacrolimus and methotrexate, for GVHD prophylaxis after unrelated donor stem cell transplant.
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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.
Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
Percentage of Patients That Experience Grade 2-4 GVHD Within 100 Days of Transplant
Tidsramme: 100 Days
|
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
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
Percentage of Patients Alive at 1 Year
Tidsramme: 1 Year
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Overall survival at 1 Year.
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1 Year
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Non-Relapse Mortality Incidence
Tidsramme: 1 year
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1 year
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Samarbeidspartnere og etterforskere
Etterforskere
- Hovedetterforsker: Pavan Reddy, MD, University of Michigan Rogel Cancer Center
Publikasjoner og nyttige lenker
Studierekorddatoer
Studer hoveddatoer
Studiestart
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Sykdommer i immunsystemet
- Neoplasmer
- Neoplasmer etter nettsted
- Hematologiske neoplasmer
- Hematologiske sykdommer
- Graft vs vertssykdom
- Fysiologiske effekter av legemidler
- Molekylære mekanismer for farmakologisk virkning
- Nukleinsyresyntesehemmere
- Enzymhemmere
- Antirevmatiske midler
- Antimetabolitter, antineoplastisk
- Antimetabolitter
- Antineoplastiske midler
- Immunsuppressive midler
- Immunologiske faktorer
- Dermatologiske midler
- Reproduktive kontrollmidler
- Abortfremkallende midler, ikke-steroide
- Aborterende midler
- Folsyreantagonister
- Calcineurin-hemmere
- Histon deacetylase-hemmere
- Metotreksat
- Takrolimus
- Vorinostat
Andre studie-ID-numre
- UMCC 2012.047 (University of Michigan University Hospital)
- HUM00070080 (Annen identifikator: University of Michigan)
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .
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