Haematological MalignanciesNCT01719341
Study of Non-Myeloablative Haplo-identical Haematopoietic Stem Cell Transplantation in Patients With Haematological Malignancies or Acquired Aplastic Anaemia
An observational study of Haematological Malignancies and Acquired Aplastic Anaemia, run by National University Hospital, Singapore at 1 site in Singapore.
Trial summary
Allogeneic haematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for patients with both haematological and some non-haematological disorders. However, one of the major limiting factors for transplantation is the inability to identify a suitable HLA-matched donor. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Haematological Malignancies, Acquired Aplastic Anaemia
- How many people
- 21 participants
- Where
- 1 siteSingapore
- Study dates
- Sep 2012to Jun 2014
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Sample size estimation based on Case and Morgan Two Stage Phase II Design with an expected duration of accrual of 2 years, assuming a power of 80% and a level of significance of 10%. With an S0 of 0.25 and SA of 0.50, an interim analysis will be performed after 14 patients are recruited with an anticipated final recruitment total of 21 patients for each arm of the study.
Who may be able to join
- Patient Selection Inclusion criteria
- Age under 70 years and older than 18 years
- Absence of HLA fully compatible related donor
- Need for an urgent transplantation, defined as within 8 weeks of referral to the transplant centre or absence of HLA-compatible VUD after searching the international registries. Patients with a HLA-compatible VUD but whose donor is considered by the transplantation centre as unsuitable will also be eligible. 4. Informed consent.
- Disease inclusion criteria:
- In general this encompasses all haematological disorders where a volunteer unrelated donor (UD) transplant is clinically indicated.
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- 1. Acute, chronic leukaemia or myelodysplastic syndrome for which allogeneic transplantation is considered as the best treatment option.
- Acute myeloid leukaemia (AML) i. 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, monosomal karyotype.
- Leukocytes at diagnosis > 50 x109/l (except in cases with good prognosis molecular rearrangements for which leukocytes should be > 100 x 109/l) b. Myelodysplastic syndromes1. International Prognosis Index (IPSS) above 1 (intermediate group 2 or high risk)
- 2. IPSS 0 or 0.5 in the presence of cytopenias requiring treatment. c. Therapy related AML or MDS in first CRd. AML or MDS in second (CR2) or subsequent CRe. 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 treatmentiii. Adults aged > 30 yearsiv. 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/Lb. In CR2 or subsequent CR 3. Non-Hodgkin's lymphomaa. Follicular NHL: in second or subsequent complete or partial remissionb. Mantle cell NHL: in second or subsequent complete or partial remissionc. High grade NHL: in second complete or very good partial remission 4. Hodgkin's diseasea. in second or subsequent complete or partial remission 5. Chronic lymphocytic leukaemia. a. in second or subsequent remissionb. with adverse risk prognostic features in first remission 6. Acquired Aplastic Anaemia 7. Myelofibrosis- Lille score -high, Cervantes score-high 8. Other haematological malignancies for which UD HSCT is indicated
Who cannot join
- Patients with an available 7-8/8 HLA-A, -B, -C, -DRB1 matched sibling donor or 7-8/8 unrelated bone marrow donor
- Availability of suitable UCB unit/s and eligible for an UCB transplant
- ECOG performance status worse than 2
- Cardiac insufficiency requiring treatment, symptomatic coronary artery disease or LVEF less than 35%.
- Hepatic disease, with total bilirubin greater than 2 times upper limit of normal or AST > 5 times upper limit of normal.
- 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.
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- Impaired renal function (creatinine > 2 times upper limit of normal or creatinine clearance < 50% for age, gender, weight).
- Previous irradiation that precludes the safe administration of an additional dose of 200 cGy of total body irradiation (TBI).
- HIV 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 uncontrolled infection e.g. active tuberculosis, mycoses or viral infection
- Serious psychiatric/ psychological disorders
- Absence of /inability to provide informed consent
- Patients with acute leukaemia with >5% bone marrow blasts
- Intermediate or high grade NHL, mantle cell NHL and Hodgkin's disease that is refractory to salvage therapy
Trial locations and contacts
1 site in 1 country.
Singapore1 site, 1 recruiting
- Recruiting
National University Hospital
Singapore, Singapore, 119074
Zi Yi Lim, MB ChB, 65 6779 5555, Zi_Yi_Lim@nuhs.edu.sg
Zi Yi Lim, MB ChB
About this study
Allogeneic haematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for patients with both haematological and some non-haematological disorders. However, one of the major limiting factors for transplantation is the inability to identify a suitable HLA-matched donor. Development of an cost-effective and clinically efficacious alternative to HLA-identical sibling or unrelated donor transplantation would significantly expand the availability of allogeneic HSCT to patients in Singapore. Preliminary results indicate that the use of high dose post-transplant cyclophosphamide (Cy) for graft versus host disease (GVHD) prophylaxis in haplo-identical allogeneic HSCT is associated a low incidence of GVHD and low treatment related toxicity. We propose a phase II clinical trial to assess the efficacy of a haplo-identical allogeneic transplantation protocol using high dose post-transplant Cy for the treatment of patients with haematological disorders. A non-myeloablative protocol (Fludarabine-low dose cyclophosphamide-TBI) will be used for patients with bone marrow failure syndromes and indolent lymphoid disease. In view of the higher relapse risk of patients with myeloid malignancies, these patients will be treated with a reduced intensity conditioning regimen (Fludarabine-Busulphan). The primary end-point of the study will be overall survival at one year. Economic cost of the haplo-identical transplantation, as well as treatment timelines will be recorded and compared will other forms of unrelated donor allogeneic transplantation (umbilical cord blood transplantation and unrelated HLA-matched adult donor). Immunological reconstitution of patients following haplo-transplantation will be analysed and data will be utilized to guide future immunotherapy strategies post-transplantation.
One year survival after non-myeloablative haploidentical stem cell transplantation is not inferior to that observed after non-myeloablative volunteer unrelated donor or unrelated cord blood haematopoietic stem cell transplantation.
What is being measured
The primary outcome is the main question the study is designed to answer.
1 year overall survival after HLA-Haploidentical transplantation
Measured: 1 year
Secondary outcomes (2)
Progression free survival one and 2 years post-transplantation
Measured: 2 years
Cumulative incidence of relapse/progression at one and 2 years post-transplant
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2012 (estimated)
- Study startSep 2012
- Primary completionJun 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Haematological MalignanciesStudies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 21 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Zi Yi Lim, MB ChB, Principal investigator, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01719341
- Sponsor's protocol ID
- 2012/00465
- Status last verified
- Dec 2013
- First submitted
- 30 Oct 2012
- Last updated
- 11 Dec 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Aversa F. Haploidentical haematopoietic stem cell transplantation for acute leukaemia in adults: experience in Europe and the United States. Bone Marrow Transplant. 2008 Mar;41(5):473-81. doi: 10.1038/sj.bmt.1705966. Epub 2008 Jan 7.
PubMed 18176612Luznik L, Bolanos-Meade J, Zahurak M, Chen AR, Smith BD, Brodsky R, Huff CA, Borrello I, Matsui W, Powell JD, Kasamon Y, Goodman SN, Hess A, Levitsky HI, Ambinder RF, Jones RJ, Fuchs EJ. High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease. Blood. 2010 Apr 22;115(16):3224-30. doi: 10.1182/blood-2009-11-251595. Epub 2010 Feb 2.
PubMed 20124511
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Non-Myeloablative Haplo-identical Haematopoietic Stem Cell Transplantation in Patients With Haematological Malignancies or Acquired Aplastic Anaemia
- ClinicalTrials.gov ID
- NCT01719341
- Acronym / sponsor ID
- 2012/00465
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 21 participants (estimated)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Study start
- Sep 2012
- Primary completion
- Jun 2014 (estimated)
- First posted
- 1 Nov 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Allogeneic haematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for patients with both haematological and some non-haematological disorders. However, one of the major limiting factors for transplantation is the inability to identify a suitable HLA-matched donor. Development of an cost-effective and clinically efficacious alternative to HLA-identical sibling or unrelated donor transplantation would significantly expand the availability of allogeneic HSCT to patients in Singapore. Preliminary results indicate that the use of high dose post-transplant cyclophosphamide (Cy) for graft versus host disease (GVHD) prophylaxis in haplo-identical allogeneic HSCT is associated a low incidence of GVHD and low treatment related toxicity. We propose a phase II clinical trial to assess the efficacy of a haplo-identical allogeneic transplantation protocol using high dose post-transplant Cy for the treatment of patients with haematological disorders. A non-myeloablative protocol (Fludarabine-low dose cyclophosphamide-TBI) will be used for patients with bone marrow failure syndromes and indolent lymphoid disease. In view of the higher relapse risk of patients with myeloid malignancies, these patients will be treated with a reduced intensity conditioning regimen (Fludarabine-Busulphan). The primary end-point of the study will be overall survival at one year. Economic cost of the haplo-identical transplantation, as well as treatment timelines will be recorded and compared will other forms of unrelated donor allogeneic transplantation (umbilical cord blood transplantation and unrelated HLA-matched adult donor). Immunological reconstitution of patients following haplo-transplantation will be analysed and data will be utilized to guide future immunotherapy strategies post-transplantation.
One year survival after non-myeloablative haploidentical stem cell transplantation is not inferior to that observed after non-myeloablative volunteer unrelated donor or unrelated cord blood haematopoietic stem cell transplantation.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Sample size estimation based on Case and Morgan Two Stage Phase II Design with an expected duration of accrual of 2 years, assuming a power of 80% and a level of significance of 10%. With an S0 of 0.25 and SA of 0.50, an interim analysis will be performed after 14 patients are recruited with an anticipated final recruitment total of 21 patients for each arm of the study.
Key inclusion criteria (11 listed)
- Patient Selection Inclusion criteria
- Age under 70 years and older than 18 years
- Absence of HLA fully compatible related donor
- Need for an urgent transplantation, defined as within 8 weeks of referral to the transplant centre or absence of HLA-compatible VUD after searching the international registries. Patients with a HLA-compatible VUD but whose donor is considered by the transplantation centre as unsuitable will also be eligible. 4. Informed consent.
- In general this encompasses all haematological disorders where a volunteer unrelated donor (UD) transplant is clinically indicated.
Key exclusion criteria (16 listed)
- Patients with an available 7-8/8 HLA-A, -B, -C, -DRB1 matched sibling donor or 7-8/8 unrelated bone marrow donor
- Availability of suitable UCB unit/s and eligible for an UCB transplant
- ECOG performance status worse than 2
- Cardiac insufficiency requiring treatment, symptomatic coronary artery disease or LVEF less than 35%.
- Hepatic disease, with total bilirubin greater than 2 times upper limit of normal or AST > 5 times upper limit of normal.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
1 year overall survival after HLA-Haploidentical transplantation
Time frame: 1 year
2 secondary outcomes
Progression free survival one and 2 years post-transplantation
Time frame: 2 years
Cumulative incidence of relapse/progression at one and 2 years post-transplant
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2013.
- Background: PubMed 18176612Aversa F. Haploidentical haematopoietic stem cell transplantation for acute leukaemia in adults: experience in Europe and the United States. Bone Marrow Transplant. 2008 Mar;41(5):473-81. doi: 10.1038/sj.bmt.1705966. Epub 2008 Jan 7.
- Background: PubMed 20124511Luznik L, Bolanos-Meade J, Zahurak M, Chen AR, Smith BD, Brodsky R, Huff CA, Borrello I, Matsui W, Powell JD, Kasamon Y, Goodman SN, Hess A, Levitsky HI, Ambinder RF, Jones RJ, Fuchs EJ. High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease. Blood. 2010 Apr 22;115(16):3224-30. doi: 10.1182/blood-2009-11-251595. Epub 2010 Feb 2.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zi Yi Lim, MB ChB principal investigator
National University Hospital, Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Haematological Malignancies and Acquired Aplastic Anaemia, run by National University Hospital, Singapore at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Zi Yi Lim, MB ChB (65 6779 5555, Zi_Yi_Lim@nuhs.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1 year overall survival after HLA-Haploidentical transplantation (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01719341, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2013.