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Donor Umbilical Cord Blood Transplant After Cyclophosphamide, Fludarabine Phosphate, and Total-Body Irradiation in Treating Patients With Hematologic Disease

23 augusti 2013 uppdaterad av: Cancer Research UK

Transplantation of Umbilical Cord Blood From Unrelated Donors in Patients With Haematological Diseases Using a Reduced Intensity Conditioning Regimen

RATIONALE: Giving low doses of chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of abnormal cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining abnormal cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening.

PURPOSE: This phase II trial is studying the side effects of donor umbilical cord blood transplant after cyclophosphamide, fludarabine phosphate, and total-body irradiation in treating patients with hematologic disease.

Studieöversikt

Status

Okänd

Betingelser

Hematopoetisk/lymfoid cancer

Intervention / Behandling

Detaljerad beskrivning

OBJECTIVES:

To assess the safety and efficacy of unrelated-donor umbilical cord blood transplantation (UCBT) using a nonmyeloablative preparative regimen in patients with hematological disease, in a multi-institution UK setting.
To confirm that unrelated-donor UCBT following nonmyeloablative conditioning is associated with consistent and durable engraftment in these patients.
To assess transplant-related mortality at day 100 associated with nonmyeloablative UCBT in these patients.
To assess the incidence of grades II-IV and III-IV acute graft-vs-host disease (GVHD) in these patients.
To assess the risk of relapse and progressive disease in these patients at 1 year post transplant after nonmyeloablative UCBT.
To assess overall and progression-free survival of these patients at 1 year after nonmyeloablative UCBT.
To assess immune reconstitution at 1, 2, 3, 6, 12, and 24 months after transplant as measured by quantitative recovery of B, T, and NK cells (flow cytometry), qualitative recovery of T cells (TREC and spectratyping), in vivo functional T-cell responses (EBV and CMV tetramers), and quantitative immunoglobulins.

OUTLINE: This is a multicenter study.

Reduced-intensity conditioning regimen: Patients receive cyclophosphamide IV over 2 hours on day -6 and fludarabine phosphate IV over 1 hour on days -6 to -2. Patients undergo a single fraction of total-body irradiation on day -1.
Umbilical cord blood (UCB) transplantation: Patients undergo umbilical cord blood transplantation on day 0.
Graft-vs-host disease prophylaxis: Patients receive cyclosporine IV or orally on days -3 to 100 followed by taper and mycophenolate mofetil IV or orally on days -3 to 35 followed by taper.

Blood and bone marrow samples are collected periodically for analysis.

After completion of study treatment, patients are followed up every 3 months in year 1, every 4 months in year 2, every 6 months until 5 years, and then annually thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK.

Studietyp

Interventionell

Inskrivning (Förväntat)

Fas

Fas 2

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

Storbritannien
- England
  - Bristol, England, Storbritannien, BS2 8BJ
    - Rekrytering
    - Bristol Royal Hospital for Children
    - Kontakt:
      
      Contact Person
      
      Telefonnummer: 44-117-342-8044
  - Leeds, England, Storbritannien, LS16 6QB
    - Rekrytering
    - Cancer Research UK Clinical Centre at St. James's University Hospital
    - Kontakt:
      
      Contact Person
      
      Telefonnummer: 44-113-206-6020
  - London, England, Storbritannien, WC1N 3JH
    - Rekrytering
    - Great Ormond Street Hospital for Children
    - Kontakt:
      
      Contact Person
      
      Telefonnummer: 44-207-813-8335
  - London, England, Storbritannien, WC1E 6DD
    - Rekrytering
    - UCL Cancer Institute
    - Kontakt:
      
      Contact Person
      
      Telefonnummer: 44-207-830-2301
  - London, England, Storbritannien, NW1 2PQ
    - Rekrytering
    - University College of London Hospitals
    - Kontakt:
      
      Rachael Hough, MD
      
      Telefonnummer: 44-845-155-5000 ext. 5239
  - Newcastle-Upon-Tyne, England, Storbritannien, NE2 4HH
    - Rekrytering
    - University of Newcastle-Upon-Tyne Northern Institute for Cancer Research
    - Kontakt:
      
      Contact Person
      
      Telefonnummer: 44-191-222-7785

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

2 år till 60 år (Barn, Vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

DISEASE CHARACTERISTICS:

Diagnosis of high-risk, advanced or poorly responding hematological disease for which a reduced-intensity hemopoietic stem cell transplantation is likely to be effective
- Disease status is such that there is no alternative therapy likely to achieve a cure or provide a significant prolongation of disease-free survival
No chronic myelogenous leukemia in first chronic phase responding to imatinib or refractory blast crisis
No acute leukemia in morphological relapse/persistent disease (defined as > 5% blasts in normocellular bone marrow)
No malignant disease that is refractory to or progressive on salvage therapy
No myelofibrosis
Donor must be matched at HLA-A and -B at antigen level and HLA-DRB1 at allelic level
- No available 5-6/6 HLA-A, -B, -DRB1 matched sibling donor OR 10/10 unrelated volunteer donor

PATIENT CHARACTERISTICS:

Karnofsky performance status (PS) 60-100% OR Lansky PS 50-100% (pediatrics)
Transaminases < 5 times upper limit of normal (ULN)
Bilirubin < 3 times ULN
Creatinine clearance > 50 mL/min
DLCO > 50% predicted
No supplemental oxygen requirements
Not pregnant or nursing
Negative pregnancy test
No HIV or HTLV (I and II) antibody positivity or evidence of infection
No acquired aplastic anemia
No decompensated congestive heart failure or uncontrolled arrhythmia and left ventricular ejection fraction ≥ 35%
No current active serious infection, in particular uncontrolled fungal infection
No congenital immune deficiencies

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
More than 6 months since prior exposure to combination chemotherapy OR only 1 course of induction combination chemotherapy for myelodysplastic syndromes or acute myeloid leukemia (please discuss with study coordinator/s if this course contained fludarabine)
At least 6 months since prior myeloablative bone marrow transplantation
No prior irradiation that precludes the safe administration of an additional dose of 200 cGy of total-body irradiation
No prior autograft

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

Primärt syfte: Behandling
Tilldelning: Icke-randomiserad
Maskning: Ingen (Open Label)

Vad mäter studien?

Primära resultatmått

Resultatmått
Non-relapse mortality at day 100

Sekundära resultatmått

Resultatmått
Incidence of grades II-IV and III-IV acute graft-vs-host disease (GVHD) at day 100 and chronic GVHD at 1 year
Mixed chimerism
Hemopoietic recovery

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Cancer Research UK

Utredare

Huvudutredare: Rachael Hough, MD, University College London Hospitals

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Allmänna publikationer

Hough R, Lopes A, Patrick P, Russell N, Raj K, Tholouli E, A Snowden J, Collin M, El-Mehidi N, Lawrie A, Clifton-Hadley L, Veys P, Craddock C, Mackinnon S, Cook G, Shaw B, Marks D. Primary graft failure, but not relapse, may be identified by early chimerism following double cord blood unit transplantation. Blood Adv. 2022 Apr 12;6(7):2414-2426. doi: 10.1182/bloodadvances.2021005106.

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart

1 januari 2009

Primärt slutförande (Förväntat)

1 augusti 2012

Studieregistreringsdatum

Först inskickad

13 augusti 2009

Först inskickad som uppfyllde QC-kriterierna