Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT00916045
Other study ID # 07CC12
Secondary ID REC - 07/H0808/1
Status Terminated
Phase Phase 2
First received June 5, 2009
Last updated February 10, 2015
Start date September 2009
Est. completion date March 2012

Study information

Verified date March 2012
Source King's College Hospital NHS Trust
Contact n/a
Is FDA regulated No
Health authority United Kingdom: Medicines and Healthcare Products Regulatory Agency
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Terminated
Enrollment 40
Est. completion date March 2012
Est. primary completion date March 2012
Accepts healthy volunteers No
Gender Both
Age group 18 Years to 70 Years
Eligibility 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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Intervention

Drug:
Thiotepa

Fludarabine

Intravenous busulphan

Thymoglobulin

Ciclosporin

Mycophenolate mofetil (MMF)

Fludarabine

Cyclophosphamide

Radiation:
Radiotherapy

Drug:
Thymoglobulin

Ciclosporin

Mycophenolate mofetil (MMF)

Fludarabine

Melphalan

Thymoglobulin

Ciclosporin

Mycophenolate mofetil (MMF)


Locations

Country Name City State
United Kingdom King's College Hosptial NHS Foundation Trust London

Sponsors (1)

Lead Sponsor Collaborator
King's College Hospital NHS Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Treatment related mortality at day 100 Day 100 Yes
Secondary Disease free survival at one year post-transplant for each cohort 1 year Yes
Secondary Chimerism Days 14 (myeloblative conditioning only), 28, 56, 100 and months 6 and 12 No
Secondary Incidence of neutrophil engraftment by day 42 Days 14, 28 and 42 Yes
Secondary Incidence of platelet engraftment by 6 months Days 14, 28, 56, 100 and month 6 Yes
Secondary Incidence of grade II-IV and III-IV acute GVHD Days 28, 56, 100 and months 6, 9, 12, 18 and 24 Yes
Secondary Incidence of chronic GVHD during the first year Day 100 and months 6 and 12 Yes
Secondary One year overall survival for each treatment cohort 1 year Yes
Secondary Incidence of systemic infections Twice a week pre-transplant to day 100 then weekly or as clinically indicated Yes
Secondary Incidence of CMV, adenovirus and EBV activation Twice a week pre-transplant to day 100 then weekly or as clinically indicated Yes
Secondary Immune reconstitution Days 14, 28, 56, 100 and months 6, 9, 12, 18 and 24 No
Secondary Dynamics of EBV infection and immunity following cord blood transplantation Days 14, 28, 56, 100 and months 6, 9 and 12 No
Secondary The development (if any) of transplant associated post transplant lymphoproliferative disease (PTLD) Days 14, 28, 56, 100 and months 6, 9 and 12 Yes
Secondary Identify any possible predictive markers for patients most at risk of PTLD development Days 14, 28, 56, 100 and months 6, 9 and 12 No
Secondary Quality of life Pre-transplant and months 6, 12, 18 and 24 No
Secondary Incidence of one year relapse or disease progression for each treatment cohort 1 year Yes
See also
  Status Clinical Trial Phase
Recruiting NCT05400122 - Natural Killer (NK) Cells in Combination With Interleukin-2 (IL-2) and Transforming Growth Factor Beta (TGFbeta) Receptor I Inhibitor Vactosertib in Cancer Phase 1
Terminated NCT04313881 - Magrolimab + Azacitidine Versus Azacitidine + Placebo in Untreated Participants With Myelodysplastic Syndrome (MDS) Phase 3
Recruiting NCT05088356 - Reduced Intensity Allogeneic HCT in Advanced Hematologic Malignancies w/T-Cell Depleted Graft Phase 1
Recruiting NCT04003220 - Idiopathic Chronic Thrombocytopenia of Undetermined Significance : Pathogenesis and Biomarker
Completed NCT02916979 - Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic SCT Using FluBuATG Phase 1
Active, not recruiting NCT03755414 - Study of Itacitinib for the Prophylaxis of Graft-Versus-Host Disease and Cytokine Release Syndrome After T-cell Replete Haploidentical Peripheral Blood Hematopoietic Cell Transplantation Phase 1
Completed NCT00003270 - Chemotherapy, Radiation Therapy, and Umbilical Cord Blood Transplantation in Treating Patients With Hematologic Cancer Phase 2
Recruiting NCT04904588 - HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide Phase 2
Terminated NCT04866056 - Jaktinib and Azacitidine In Treating Patients With MDS With MF or MDS/MPN With MF. Phase 1/Phase 2
Recruiting NCT04701229 - Haploinsufficiency of the RBM22 and SLU7 Genes in Del(5q) Myelodysplastic Syndromes
Suspended NCT04485065 - Safety and Efficacy of IBI188 With Azacitidine in Subjects With Newly Diagnosed Higher Risk MDS Phase 1
Recruiting NCT04174547 - An European Platform for Translational Research in Myelodysplastic Syndromes
Enrolling by invitation NCT04093570 - A Study for Participants Who Participated in Prior Clinical Studies of ASTX727 (Standard Dose), With a Food Effect Substudy at Select Study Centers Phase 2
Completed NCT02508870 - A Study of Atezolizumab Administered Alone or in Combination With Azacitidine in Participants With Myelodysplastic Syndromes Phase 1
Completed NCT04543305 - A Study of PRT1419 in Patients With Relapsed/Refractory Hematologic Malignancies Phase 1
Recruiting NCT05384691 - Efficacy of Luspatercept in ESA-naive LR-MDS Patients With or Without Ring Sideroblasts Who do Not Require Transfusions Phase 2
Recruiting NCT05365035 - A Phase II Study of Cladribine and Low Dose Cytarabine in Combination With Venetoclax, Alternating With Azacitidine and Venetoclax, in Patients With Higher-risk Myeloproliferative Chronic Myelomonocytic Leukemia or Higher-risk Myelodysplastic Syndromes With Excess Blasts Phase 2
Recruiting NCT06008405 - Clinical Trial Evaluating the Safety of the TQB2928 Injection Combination Therapy Phase 1
Not yet recruiting NCT05969821 - Clonal Hematopoiesis of Immunological Significance
Withdrawn NCT05170828 - Cryopreserved MMUD BM With PTCy for Hematologic Malignancies Phase 1