Pilot Study of Unrelated Cord Blood Transplantation

NCT00916045 | Terminated Phase 2

• 3 other identifiers: 07CC12REC - 07/H0808/193EudraCT - 2007-001657-26
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Leukemia, Lymphoblastic, Acute; Lymphoma, Non-Hodgkin; Hodgkin Disease; Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Treatment related mortality at day 100

  Day 100

Secondary Outcomes (15)

• Disease free survival at one year post-transplant for each cohort

  1 year

• Chimerism

  Days 14 (myeloblative conditioning only), 28, 56, 100 and months 6 and 12

• Incidence of neutrophil engraftment by day 42

  Days 14, 28 and 42

• Incidence of platelet engraftment by 6 months

  Days 14, 28, 56, 100 and month 6

• Incidence of grade II-IV and III-IV acute GVHD

  Days 28, 56, 100 and months 6, 9, 12, 18 and 24

Study Arms (3)

Myeloblative conditioning regimen

OTHER

Drug: Thiotepa; Drug: Fludarabine; Drug: Intravenous busulphan; Drug: Thymoglobulin; Drug: Ciclosporin; Drug: Mycophenolate mofetil (MMF)

Reduced intensity conditioning regimen - FluCyTBI

OTHER

Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Radiotherapy; Drug: Thymoglobulin; Drug: Ciclosporin; Drug: Mycophenolate mofetil (MMF)

Reduced intensity conditioning regimen - FluMel

OTHER

Drug: Fludarabine; Drug: Melphalan; Drug: Thymoglobulin; Drug: Ciclosporin; Drug: Mycophenolate mofetil (MMF)

Interventions

Thiotepa DRUG

Myeloblative conditioning regimen

Fludarabine DRUG

Myeloblative conditioning regimen

Intravenous busulphan DRUG

Also known as: Busilvex

Myeloblative conditioning regimen

Thymoglobulin DRUG

Myeloblative conditioning regimen

Ciclosporin DRUG

Myeloblative conditioning regimen

Mycophenolate mofetil (MMF) DRUG

Myeloblative conditioning regimen

Cyclophosphamide DRUG

Reduced intensity conditioning regimen - FluCyTBI

Radiotherapy RADIATION

Reduced intensity conditioning regimen - FluCyTBI

Melphalan DRUG

Reduced intensity conditioning regimen - FluMel

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In general this encompasses all haematological disorders where a volunteer unrelated donor transplant is clinically indicated.
• Acute, chronic leukaemia or myelodysplastic syndrome for which allogeneic transplantation is considered as the best treatment option.
• 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)
• 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.
• Therapy related AML or MDS in first CR
• AML or MDS in second (CR2) or subsequent CR
• 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
• 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

You may not qualify if:

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

Sponsors & Collaborators

• King's College Hospital NHS Trust: lead

Study Sites (1)

King's College Hosptial NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Non-Hodgkin; Hodgkin Disease; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Thiotepa; fludarabine; Busulfan; thymoglobulin; Cyclosporine; Mycophenolic Acid; Cyclophosphamide; Radiotherapy; Melphalan

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Therapeutics; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids

Study Officials

• Antonio Pagliuca, MBBS, MA, FRCP, FRCPath

  King's College Hospital NHS Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 5, 2009
• First Posted: June 8, 2009
• Study Start: September 1, 2009
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: February 11, 2015

Record last verified: 2012-03

Locations

GB (1)