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AzTrials

LeukemiaPhase 2NCT02638467

Allogeneic Stem Cell Transplantation in Chronic Myeloid Leukemia Failing TKIs Therapy

A Phase 2 study testing Bosutinib, Bone Marrow Transplant and Bone Marrow cells in people with Leukemia and Myelogenous, run by University of Milano Bicocca at 2 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Patients newly diagnosed with chronic phase chronic myeloid leukemia undergo treatment with TK inhibitors (TKI). A possible cause of TK failure is represented by the insufficient recovery of normal Ph- hematopoiesis during TKI treatment, with consequent severe cytopenias that limit TKI adequate administration. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Leukemia, Myelogenous, Chronic
What is being tested?
Bosutinib, Bone Marrow Transplant and Bone Marrow cells
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
2 sitesItaly
Study dates
Nov 2015to Feb 2020
Phase
Phase 2
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

Who may be able to join

  • Chronic Myeloid Leukaemia -CML- in chronic phase (CP)
  • Failure to achieve at least a Major Cytogenetic Response (MCyR) after a minimum of 18 months of TKIs treatment
  • Inability to tolerate 3 months of uninterrupted full dose TKIs therapy due to hematological toxicity
  • A minimum of three treatment interruptions due to hematological toxicity Availability of a HLA-identical related donor (Matched Related Donor, MRD)
  • Availability of unrelated donor (Matched Unrelated Donor, MUD) satisfying the criteria of a 10/10 antigen match at (Human Leukocyte Antigen) HLA-A, -B, -C and - DRB1, -DQB1 at high resolution typing, or 9/10 with a permissive - DP disparity according to Fleischhauer model (Crocchiolo et al, Blood 2009)
  • Target graft size (bone marrow):
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  • bone marrow: > 3 x 106 CD34+ cells/kg BW recipient or > 3 x 108 nucleated cells/kg BW
  • Karnofsky Index > 80 %
  • Age ≥18 and ≤70 years
  • Adequate contraception in female patients of child-bearing potential
  • Written informed consent

Who cannot join

  • Secondary malignancies
  • A hematopoietic cell transplantation-specific comorbidity index (Sorror et al Appendix C) > 4
  • Known and manifested malignant involvement of the Central Nervous System (CNS)
  • Active infectious disease
  • Active human immunodeficiency virus (HIV), Hepatitis B virus (HBV) or Hepatitis B virus (HCV) infection
  • Impaired liver function (Bilirubin > upper normal limit; Transaminases > 3.0 x upper normal limit)
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  • Impaired renal function (Creatinine-clearance < 60 ml/min; Serum Creatinine > 1.5 x upper normal limit).
  • Pleural effusion or ascites > 1.0 L
  • Pregnancy or lactation
  • Known hypersensitivity to Busilvex and/or fludarabine 11 Non-co-operative behaviour or non-compliance 12 Psychiatric diseases or conditions that might impair the ability to give informed consent

Trial locations and contacts

2 sites in 1 country.

Italy2 sites

  • Ospedale San Raffaele

    Milan, MI, 20132

  • ASST-Monza

    Monza, Italy/MB, 20900

Other trials in Italy

About this study

Official title: Allogeneic Haematopoietic Stem Cell Transplantation From a Matched Donor in Patients With Chronic Myeloid Leukemia Failing to Gain Normal Hemopoiesis Under TKIs Therapy

Patients newly diagnosed with chronic phase chronic myeloid leukemia undergo treatment with TK inhibitors (TKI). A possible cause of TK failure is represented by the insufficient recovery of normal Ph- hematopoiesis during TKI treatment, with consequent severe cytopenias that limit TKI adequate administration. Although rare, this event happens in a proportion of 4-5% of CML patients. Our hypothesis is to circumvent this peculiar condition by providing a normal hematopoiesis from a HLA-matched donor (Human Leukocyte Antigen). The transplant procedure is therefore intended in providing a sustained hematopoiesis that will allow an early treatment with an adequate dosing of TKI. The transplant procedure planned in our study is built on all available evidences to provide the lowest incidence of acute and chronic GvHD (Graft-versus-host disease). Therefore, a bone marrow will be the preferential source and a GvHD prophylaxis based on Anti-thrombocyte globulin (ATG) and Cyclosporine/Methotrexate will be used according to standard current experience in the field of family and unrelated donors. The pre-transplant TKI will be continued until aplasia will develop, in order to decrease the tumor load as much as possible.The use of TKIs shortly after transplant carries the risk of inhibiting the newly transplanted hematopoietic cells, as Kit, an important kinase in normal bone marrow cells, is frequently blocked by Abl inhibitors. The use of bosutinib as post-transplant therapy is justified by the lack of Kit inhibition that distinguishes bosutinib from all other TKIs, and which could allow a minimal inhibitory activity against the transplanted normal bone marrow.

Being tested
Bosutinib, Bone Marrow Transplant, Bone Marrow cells
Medical subject headings
Leukemia, Bronchiolitis Obliterans Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BosutinibDrug

    Also called Bosulif, SKI-606

    Subjects will receive 400mg of bosutinib once daily from day +30 after transplant, by mouth with food, preferably in the morning. Bosutinib will also be administered from day at least -45 to day -15 to assess the sensitivity of patient CML to this TKI.

  • Bone Marrow TransplantProcedure or surgery

    Samples of the unrelated stem cell graft shall be characterised with respect to the number of CD34 positive cells per kg body weight of the recipient.

    The number of transplanted CD34 positive cells per kg body weight (BW) of the recipient shall be recorded in the Case Report Form (CRF). If the transplant was cryopreserved the number of viable CD34 positive cells has to be determined after thawing and documented.

    The goal is to transplant > 3 x 106 CD34+ cells/kg BW recipient from bone marrow or > 3 x 108 nucleated cells/kg BW recipient from bone marrow

  • Bone Marrow cellsDrug

Study groups in NCT02638467
Study groupRoleWhat they receive
Bosutinib and Bone Marrow TransplantExperimentalSubjects will receive 400mg of bosutinib from day at least -45 to day -15 to assess the sensitivity of patient Chronic Myeloid Leukemia (CML) to this TKI. Patients will be transplanted with the aim to transplant > 3 x 106 CD34+ cells/kg Body Weight (BW) recipient from bone marrow or > 3 x 108 nucleated cells/kg BW recipient from bone marrow. Then, subjects will receive 400mg of bosutinib once daily from day +30 after transplant.
Receives: Drug: Bosutinib; Procedure: Bone Marrow Transplant; Drug: Bone Marrow cells

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Efficacy as assessed by the percentage of patients with Complete Cytogenetic Response (CCyR)

    The percentage of patients with Complete Cytogenetic Response (CCyR) will be calculated as the complement to the percentage of failures on the total number of patients treated, where failure includes the following events: no engraftment, death within 12 months, no CCyR at 12 months.

    Measured: 12 months

Secondary outcomes (13)

  1. Overall Survival

    Measured: 12 months

  2. Percentage of patients with engraftment

    Measured: 12 months

  3. percentage of patients with complete chimerism (95%)

    Measured: Day +28, +56 and +100

  4. Evaluation of Major Cytogenetic Response (MCyR)

    Major Cytogenetic Response (MCyR) is < 36% Ph+ metaphases

    Measured: 12 months

  5. Evaluation of molecular responses

    Molecular response is defined

    • Complete: if there is undetectable BCR-ABL transcript
    • Major: if ratio BCR/ABL <= 0.1% on International Scale

    Measured: 12 months

  6. Relapse incidence (RI)

    Measured: 12 months

  7. Incidence of non-relapse mortality (NRM)

    Measured: Within day +28 and +360

  8. Incidence and severity of acute and chronic graft vs. host disease (GvHD)

    Measured: 12 months

  9. Quality of Life (QoL)

    Evaluation of QoL with EQ-5D-5L (Italian - Version 2) and FACT-Leu (Italian -Version 4)

    Measured: 12 months

  10. Overall Survival (OS)

    2 years after transplantation of the last patient included (this is intended to allow evaluations of all expected major molecular responses)

    Measured: 36 months

  11. Progression Free Survival (PFS)

    2 years after transplantation of the last patient included (this is intended to allow evaluations of all expected major molecular responses)

    Measured: 36 months

  12. Relapse Incidence (RI)

    2 years after transplantation of the last patient included (this is intended to allow evaluations of all expected major molecular responses)

    Measured: 36 months

  13. Chronic Graft-versus-host Disease (cGvHD)

    2 years after transplantation of the last patient included (this is intended to allow evaluations of all expected major molecular responses)

    Measured: 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Dec 2015 (estimated)
  2. Study startNov 2015
  3. Primary completion29 Nov 2018
  4. Study completionFeb 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02638467
Sponsor's protocol ID
alloCML
Status last verified
Nov 2020
First submitted
9 Dec 2015
Last updated
5 Nov 2020
Results posted
No
Data monitoring committee
Yes

Publications

  • Redaelli A, Bell C, Casagrande J, Stephens J, Botteman M, Laskin B, Pashos C. Clinical and epidemiologic burden of chronic myelogenous leukemia. Expert Rev Anticancer Ther. 2004 Feb;4(1):85-96. doi: 10.1586/14737140.4.1.85.

    PubMed 14748660

  • Heisterkamp N, Stephenson JR, Groffen J, Hansen PF, de Klein A, Bartram CR, Grosveld G. Localization of the c-ab1 oncogene adjacent to a translocation break point in chronic myelocytic leukaemia. Nature. 1983 Nov 17-23;306(5940):239-42. doi: 10.1038/306239a0.

    PubMed 6316147

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bosutinib, Bone Marrow Transplant and Bone Marrow cells in people with Leukemia and Myelogenous, run by University of Milano Bicocca at 2 sites in Italy.

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 10 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: finished, as of the sponsor's last update on 5 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Italy. 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy as assessed by the percentage of patients with Complete Cytogenetic Response (CCyR) (time frame: 12 months). 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 NCT02638467, 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 5 Nov 2020.

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