Pilot Study of Unrelated Cord Blood Transplantation

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2009 by King's College Hospital NHS Trust.
Recruitment status was  Not yet recruiting
Sponsor:
Information provided by:
King's College Hospital NHS Trust
ClinicalTrials.gov Identifier:
NCT00916045
First received: June 5, 2009
Last updated: NA
Last verified: May 2009
History: No changes posted
  Purpose

The purpose of this study is to determine the safety and feasibility of unrelated double and single cord blood transplantation in patients with haematological malignancies using reduced-intensity or myeloablative conditioning regimens.


Condition Intervention Phase
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Leukemia, Lymphoblastic, Acute
Lymphoma, Non-Hodgkin
Hodgkin Disease
Chronic Lymphocytic Leukemia
Drug: Thiotepa
Drug: Fludarabine
Drug: Intravenous busulphan
Drug: Thymoglobulin
Drug: Ciclosporin
Drug: Mycophenolate mofetil (MMF)
Drug: Cyclophosphamide
Radiation: Radiotherapy
Drug: Melphalan
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study of Unrelated Cord Blood Transplantation in Patients With Poor Risk Haematological Malignancies

Resource links provided by NLM:


Further study details as provided by King's College Hospital NHS Trust:

Primary Outcome Measures:
  • Treatment related mortality at day 100 [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Disease free survival at one year post-transplant for each cohort [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Chimerism [ Time Frame: Days 14 (myeloblative conditioning only), 28, 56, 100 and months 6 and 12 ] [ Designated as safety issue: No ]
  • Incidence of neutrophil engraftment by day 42 [ Time Frame: Days 14, 28 and 42 ] [ Designated as safety issue: Yes ]
  • Incidence of platelet engraftment by 6 months [ Time Frame: Days 14, 28, 56, 100 and month 6 ] [ Designated as safety issue: Yes ]
  • Incidence of grade II-IV and III-IV acute GVHD [ Time Frame: Days 28, 56, 100 and months 6, 9, 12, 18 and 24 ] [ Designated as safety issue: Yes ]
  • Incidence of chronic GVHD during the first year [ Time Frame: Day 100 and months 6 and 12 ] [ Designated as safety issue: Yes ]
  • One year overall survival for each treatment cohort [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Incidence of systemic infections [ Time Frame: Twice a week pre-transplant to day 100 then weekly or as clinically indicated ] [ Designated as safety issue: Yes ]
  • Incidence of CMV, adenovirus and EBV activation [ Time Frame: Twice a week pre-transplant to day 100 then weekly or as clinically indicated ] [ Designated as safety issue: Yes ]
  • Immune reconstitution [ Time Frame: Days 14, 28, 56, 100 and months 6, 9, 12, 18 and 24 ] [ Designated as safety issue: No ]
  • Dynamics of EBV infection and immunity following cord blood transplantation [ Time Frame: Days 14, 28, 56, 100 and months 6, 9 and 12 ] [ Designated as safety issue: No ]
  • The development (if any) of transplant associated post transplant lymphoproliferative disease (PTLD) [ Time Frame: Days 14, 28, 56, 100 and months 6, 9 and 12 ] [ Designated as safety issue: Yes ]
  • Identify any possible predictive markers for patients most at risk of PTLD development [ Time Frame: Days 14, 28, 56, 100 and months 6, 9 and 12 ] [ Designated as safety issue: No ]
  • Quality of life [ Time Frame: Pre-transplant and months 6, 12, 18 and 24 ] [ Designated as safety issue: No ]
  • Incidence of one year relapse or disease progression for each treatment cohort [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: June 2009
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Myeloblative conditioning regimen Drug: Thiotepa Drug: Fludarabine Drug: Intravenous busulphan
Other Name: Busilvex
Drug: Thymoglobulin Drug: Ciclosporin Drug: Mycophenolate mofetil (MMF)
Reduced intensity conditioning regimen - FluCyTBI Drug: Fludarabine Drug: Cyclophosphamide Radiation: Radiotherapy Drug: Thymoglobulin Drug: Ciclosporin Drug: Mycophenolate mofetil (MMF)
Reduced intensity conditioning regimen - FluMel Drug: Fludarabine Drug: Melphalan Drug: Thymoglobulin Drug: Ciclosporin Drug: Mycophenolate mofetil (MMF)

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE INCLUSION CRITERIA:

In general this encompasses all haematological disorders where a volunteer unrelated donor transplant is clinically indicated.

  1. Acute, chronic leukaemia or myelodysplastic syndrome for which allogeneic transplantation is considered as the best treatment option.

    1. Acute myeloid leukaemia (AML) in first complete remission (CR1) with one of the following characteristics:

      • High risk cytogenetic or molecular alterations (e.g. t(9;22), deletion 7/7q-, monosomy 5 or del(5q), 3q26 alterations, complex karyotype [3 or more anomalies], p53 alterations, 11q23 especially t(6;11) abnormalities, FLT-3 ITD)
      • Leukocytes at diagnosis > 50 x109/l (except in cases with good prognosis molecular rearrangements for which leukocytes should be > 100 x 109/l)
    2. Myelodysplastic syndromes

      • International Prognosis Index (IPSS) above 1 (intermediate group 2 or high risk)
      • IPSS 0 or 0.5 in the presence of cytopenias requiring treatment.
    3. Therapy related AML or MDS in first CR
    4. AML or MDS in second (CR2) or subsequent CR
    5. Ph'-positive chronic myeloid leukaemia

    i. In first chronic phase if refractory and/or intolerance to tyrosine kinase inhibitors is clearly demonstrated ii. In second chronic phase

  2. Acute lymphoblastic leukaemia (ALL)

    a. In CR1 with one of the following characteristics: i. Very high risk chromosome or molecular alterations (e.g. t(9;22), t(4;11), complex karyotype in adults, bcr/abl rearrangements, MLL rearrangements) ii. Slow response to induction treatment defined as the presence of >10% blasts in bone marrow at day 14 of induction treatment iii. Adults aged > 30 years iv. Adults with B ALL cell line with a number of leukocytes at diagnosis >25 x 109/L or T ALL cell line with a number of leukocytes at diagnosis >100X109/L

    b. In CR2 or subsequent CR

  3. Non-Hodgkin's lymphoma

    1. Follicular NHL: in second or subsequent complete or partial remission
    2. Mantle cell NHL: in second or subsequent complete or partial remission
    3. High grade NHL: in second complete or very good partial remission
  4. Hodgkin's disease

    a. in second or subsequent complete or partial remission

  5. Chronic lymphocytic leukaemia.

    1. in second or subsequent remission
    2. with adverse risk prognostic features in first remission
  6. Acquired bone marrow failure syndromes
  7. Other haematological malignancies for which UD bone marrow transplantation is indicated

PATIENT SELECTION

Inclusion criteria: myeloablative conditioning regimen

  1. Aged under 35 years and greater than 18 years
  2. Absence of HLA compatible related donor.
  3. Need for an urgent transplantation or absence of HLA-compatible VUD after searching the international registries.
  4. Patients with a HLA-compatible VUD but whose donor is considered by the transplantation centre as unsuitable will also be eligible.
  5. Availability of suitable UD-UCB unit/s.
  6. Informed consent.

Exclusion criteria: myeloablative conditioning regimen

  1. Patients with an available 5-6/6 HLA-A, -B, -DRB1 matched sibling donor or 10/10 unrelated bone marrow donor
  2. ECOG performance status worse than 2
  3. Cardiac insufficiency requiring treatment, symptomatic coronary artery disease or LVEF less than 40%.
  4. Hepatic disease, with total bilirubin above 20umol/l or AST > 3 times upper limit of normal.
  5. Severe hypoxaemia, pO2 < 70 mm Hg, with decreased DLCO < 70% of predicted; or mild hypoxemia, pO2 < 80 mm Hg with severely decreased DLCO < 60% of predicted.
  6. Impaired renal function (creatinine > 2 times upper limit of normal or creatinine clearance < 50% for age, gender, weight).
  7. Patients who have received previous treatment with Thymoglobulin®
  8. HIV or HTLV positive patients.
  9. Female patients who are pregnant or breast feeding due to risks to foetus from conditioning regimen and potential risks to nursing infants.
  10. Life expectancy severely limited by diseases other than the disease indication for transplant
  11. Serious concurrent untreated infection e.g. active tuberculosis, mycoses or viral infection
  12. Serious psychiatric/ psychological disorders
  13. Absence of /inability to provide informed consent
  14. Serious diseases that prevent treatments with chemotherapy
  15. Myelofibrosis

Inclusion criteria: reduced-intensity conditioning regimen (For both FluMel & FluCyTBI regimens):

  1. Age under 70 years and older than 18 years
  2. Absence of HLA compatible related donor.
  3. Need for an urgent transplantation or absence of HLA-compatible VUD after searching the international registries.
  4. Patients with a HLA-compatible VUD but whose donor is considered by the transplantation centre as unsuitable will also be eligible.
  5. Availability of suitable UD-UCB unit/s.
  6. Informed consent.

Exclusion Criteria: reduced-intensity conditioning regimen (For both FluMel & FluCyTBI regimens):

  1. Patients with an available 5-6/6 HLA-A, -B, -DRB1 matched sibling donor or 10/10 unrelated bone marrow donor
  2. ECOG performance status worse than 2
  3. Cardiac insufficiency requiring treatment, symptomatic coronary artery disease or LVEF less than 35%.
  4. Hepatic disease, with total bilirubin greater than 2 times upper limit of normal or AST > 5 times upper limit of normal.
  5. Severe hypoxaemia, pO2 < 70 mm Hg, with decreased DLCO < 50% of predicted; or mild hypoxemia, pO2 < 80 mm Hg with severely decreased DLCO < 50% of predicted.
  6. Impaired renal function (creatinine > 2 times upper limit of normal or creatinine clearance < 50% for age, gender, weight).
  7. Previous irradiation that precludes the safe administration of an additional dose of 200 cGy of total body irradiation (TBI).
  8. Patients who have received previous treatment with Thymoglobulin®
  9. HIV or HTLV positive patients.
  10. Female patients who are pregnant or breast feeding due to risks to foetus from conditioning regimen and potential risks to nursing infants.
  11. Life expectancy severely limited by diseases other than the disease indication for transplant
  12. Serious concurrent uncontrolled infection e.g. active tuberculosis, mycoses or viral infection
  13. Serious psychiatric/ psychological disorders
  14. Absence of /inability to provide informed consent
  15. Within 6 months of prior myeloablative transplant.
  16. Patients with acute leukaemia in morphological relapse/ persistent/ progressive disease
  17. Intermediate or high grade NHL, mantle cell NHL and Hodgkin's disease that is refractory or progressive on salvage therapy.
  18. Myelofibrosis
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00916045

Contacts
Contact: Antonio Pagliuca, MBBS, MA, FRCP, FRCPath 020 3299 9000 ext 3709 tony.pagliuca@kch.nhs.uk

Locations
United Kingdom
King's College Hosptial NHS Foundation Trust Not yet recruiting
London, United Kingdom, SE5 9RS
Contact: Antonio Pagliuca, MBBS, MA, FRCP, FRCPath    020 3299 9000 ext 3709    tony.pagliuca@kch.nhs.uk   
Sponsors and Collaborators
King's College Hospital NHS Trust
Investigators
Principal Investigator: Antonio Pagliuca, MBBS, MA, FRCP, FRCPath King's College Hospital NHS Trust
  More Information

No publications provided

Responsible Party: Dr Antonio Pagliuca, King's College Hospital NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT00916045     History of Changes
Other Study ID Numbers: 07CC12, REC - 07/H0808/193, EudraCT - 2007-001657-26
Study First Received: June 5, 2009
Last Updated: June 5, 2009
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Hodgkin Disease
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Lymphoma
Lymphoma, Non-Hodgkin
Myelodysplastic Syndromes
Preleukemia
Hematologic Neoplasms
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms by Site
Busulfan
Cyclophosphamide
Cyclosporins
Cyclosporine
Melphalan
Mycophenolate mofetil
Thiotepa

ClinicalTrials.gov processed this record on April 23, 2014