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Acute Lymphoblastic LeukemiaPhase 2NCT01025778

Haploidentical Stem Cell Transplantation for Children With Therapy Resistant Leukemia

A Phase 2 study testing Clofarabine for remission induction, Etoposide for remission induction and Cyclophosphamide for remission induction in people with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia, run by Lund University Hospital at 1 site in Sweden.

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

Despite substantial progress in the treatment pediatric acute leukemia a significant number of children will experience primary or secondary resistance to the treatment. In other words it will be not possible to achieve remission using standard chemotherapy (primary resistance) or the patients will develop… Read more about this study

Who is it for?
Ages 1 year to 21 years
What is being tested?
Clofarabine for remission induction, Etoposide for remission induction and Cyclophosphamide for remission induction
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
1 siteSweden
Study dates
Dec 2009to Dec 2012
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 1 year to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Target population
  • Refractory acute lymphoblastic leukemia
  • Chemoresistant isolated or combined bone marrow relapse
  • Relapse after during/after conventional treatment
  • Relapse ≥6 months after allogeneic stem cell transplantation
  • Primary induction failure
Show all 37Show fewer
  • Isolated extramedullary relapse after previous HSCT (>6 months)
  • Refractory acute myeloblastic leukemia including sAML
  • Chemoresistant relapse
  • Relapse after during/after conventional treatment
  • Relapse ≥6 months after allogeneic stem cell transplantation
  • Primary induction failure
  • Inclusion criteria to start induction treatment with multidrug regimen
  • Age ≥ 1 and ≤21 years
  • Patients with previous HCST ≥ 6 m
  • Provide signed written informed consent patients', and patients' parents /guardians
  • Older children should be capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent as well.
  • Cardiac output SF ≥25%
  • Have adequate renal and hepatic functions as indicated by the following laboratory values:
  • Calculated creatinine clearance ≥90 ml/min/1.73 m2
  • Serum bilirubin ≤1.5 X upper limit of normal (ULN)
  • Aspartate transaminase (AST)/alanine transaminase (ALT) ≤2.5 X ULN
  • Alkaline phosphatase ≤ 2.5 X ULN
  • Performance score of ≥70% (Lansky or Karnofsky)
  • A suitable haploidentical family member available for stem cell donation, > 18 years of age, fulfilling institutional criteria for blood and marrow donation.
  • Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.
  • Cardiac output SF ≥25%
  • Have adequate renal and hepatic functions as indicated by the following laboratory values:
  • Calculated creatinine clearance ≥90 ml/min/1.73 m2
  • Serum bilirubin ≤1.5 X upper limit of normal (ULN)
  • Aspartate transaminase (AST)/alanine transaminase (ALT) ≤2.5 X ULN
  • Alkaline phosphatase ≤ 2.5 X ULN
  • Performance score of ≥70% (Lansky or Karnofsky)
  • A suitable haploidentical family member available for stem cell donation, > 18 years of age, fulfilling institutional criteria for blood and marrow donation.
  • Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent.
  • Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment.
  • Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.

Who cannot join

  • Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
  • Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea.
  • The patient must have recovered from all acute toxicities from any previous therapy.
  • Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment.
  • Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
  • Pregnant or lactating patients.
  • Any significant concurrent malignant disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.

Trial locations and contacts

1 site in 1 country.

Sweden1 site

  • Lund University Hospital

    Lund, SE-22185

Other trials in Sweden

About this study

Official title: Clofarabine Based Remission Induction Followed by Haploidentical Stem Cell Transplantation in Children With Refractory Hematological Malignancies

Despite substantial progress in the treatment pediatric acute leukemia a significant number of children will experience primary or secondary resistance to the treatment. In other words it will be not possible to achieve remission using standard chemotherapy (primary resistance) or the patients will develop chemotherapy resistant relapse (secondary resistance). Children failing to achieve remission or children relapsing after previous allogeneic stem cell transplantation have short life expectancy and palliative treatment still remains the most reasonable option as the escalation of conventional chemotherapy is not longer effective.

The role of Graft versus Leukemia effect was postulated as one of the mechanisms contributing to the leukemia control/eradication after transplantation of hematopoietic stem cells.

In this study the investigators combine intensified multiagent Clofarabine containing chemotherapy with post-induction treatment intensification using reduced intensity conditioning followed by haploidentical hematopoietic stem cell transplantation. Introducing a new drug to the treatment of resistant leukemia the investigators want to achieve a response which allows us to proceed to immediate haploidentical transplantation. Using a haploidentical donor the investigators can avoid time consuming search for an unrelated donor and perform the transplantation at the optimal time-point. Combating therapy resistant leukemia the investigators would like to evoke and utilize potential Graft-versus-Leukemia effect which is much more pronounced in the haploidentical setting, as it is well documented that allogeneic transplantation with a matched donor is not effective in resistant disease. The use of best KIR mismatch donor and post-transplant donor lymphocyte infusion will be implemented in order to develop/intensify graft versus leukemia effect.

Being tested
Clofarabine for remission induction, Etoposide for remission induction, Cyclophosphamide for remission induction, Clofarabine in conditioning before transplantation, Thiotepa in conditioning before transplantation
Keywords
Haploidentical hematopoietic stem cell transplantation, Graft versus host disease, Donor lymphocyte infusion, Graft versus leukemia effect, Immunological recovery, Bridge to transplant approach, Therapy resistant leukemia, Hematological malignancy
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Graft vs Host Disease, Hematologic Neoplasms

What participants receive

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

  • Clofarabine for remission inductionDrug

  • Etoposide for remission inductionDrug

  • Cyclophosphamide for remission inductionDrug

  • Clofarabine in conditioning before transplantationDrug

  • Thiotepa in conditioning before transplantationDrug

  • Melfalan in conditioning before transplantationDrug

  • Haploidentical transplantation of T-cell depleted graftProcedure or surgery

  • Donor lymphocyte infusionProcedure or surgery

Study groups in NCT01025778
Study groupRoleWhat they receive
Remission induction and haplo-SCTExperimentalRemission induction with Clofaranie, Etoposide and Cyclophosphamide combination followed by haplidentical stem cella transplantation if remission achieved.
Receives: Drug: Clofarabine for remission induction; Drug: Etoposide for remission induction; Drug: Cyclophosphamide for remission induction; Drug: Clofarabine in conditioning before transplantation; Drug: Thiotepa in conditioning before transplantation; Drug: Melfalan in conditioning before transplantation; Procedure: Haploidentical transplantation of T-cell depleted graft; Procedure: Donor lymphocyte infusion

What is being measured

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

  1. Event free survival

    Measured: 1 year from transplantation

Secondary outcomes (4)

  1. Evaluation of induction efficacy by response rate and the number of children proceeding to transplant

    Measured: 3 months from induction start

  2. Tolerance, safety and quality of life

    Measured: 1 year from transplantation

  3. Hematological and immunological recovery

    Measured: 100 days fron tranplantation

  4. Incidence of graft versus host disease

    Measured: 100 days from transplantation

Timeline

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

  1. First posted4 Dec 2009 (estimated)
  2. Study startDec 2009
  3. Primary completionDec 2012
  4. Study completionDec 2012

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
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01025778
Sponsor's protocol ID
BUS2009/1
Status last verified
Feb 2021
First submitted
3 Dec 2009
Last updated
21 Feb 2021
Results posted
No
Data monitoring committee
No

Publications

  • Locatelli F, Testi AM, Bernardo ME, Rizzari C, Bertaina A, Merli P, Pession A, Giraldi E, Parasole R, Barberi W, Zecca M. Clofarabine, cyclophosphamide and etoposide as single-course re-induction therapy for children with refractory/multiple relapsed acute lymphoblastic leukaemia. Br J Haematol. 2009 Nov;147(3):371-8. doi: 10.1111/j.1365-2141.2009.07882.x. Epub 2009 Aug 29.

    PubMed 19747360

  • Hijiya N, Gaynon P, Barry E, Silverman L, Thomson B, Chu R, Cooper T, Kadota R, Rytting M, Steinherz P, Shen V, Jeha S, Abichandani R, Carroll WL. A multi-center phase I study of clofarabine, etoposide and cyclophosphamide in combination in pediatric patients with refractory or relapsed acute leukemia. Leukemia. 2009 Dec;23(12):2259-64. doi: 10.1038/leu.2009.185. Epub 2009 Sep 10.

    PubMed 19741725

  • Stern M, Ruggeri L, Mancusi A, Bernardo ME, de Angelis C, Bucher C, Locatelli F, Aversa F, Velardi A. Survival after T cell-depleted haploidentical stem cell transplantation is improved using the mother as donor. Blood. 2008 Oct 1;112(7):2990-5. doi: 10.1182/blood-2008-01-135285. Epub 2008 May 20.

    PubMed 18492955

  • Jeha S, Gaynon PS, Razzouk BI, Franklin J, Kadota R, Shen V, Luchtman-Jones L, Rytting M, Bomgaars LR, Rheingold S, Ritchey K, Albano E, Arceci RJ, Goldman S, Griffin T, Altman A, Gordon B, Steinherz L, Weitman S, Steinherz P. Phase II study of clofarabine in pediatric patients with refractory or relapsed acute lymphoblastic leukemia. J Clin Oncol. 2006 Apr 20;24(12):1917-23. doi: 10.1200/JCO.2005.03.8554.

    PubMed 16622268

  • Toporski J, Krol L, Dykes J, Hakansson Y, Pronk C, Turkiewicz D. The combination of clofarabine, etoposide, and cyclophosphamide shows limited efficacy as a bridge to transplant for children with refractory acute leukemia: results of a monitored prospective study. Pediatr Hematol Oncol. 2021 Apr;38(3):216-226. doi: 10.1080/08880018.2020.1838012. Epub 2020 Nov 5.

    PubMed 33150834

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Clofarabine for remission induction, Etoposide for remission induction and Cyclophosphamide for remission induction in people with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia, run by Lund University Hospital at 1 site in Sweden.

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 37 inclusion and 7 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 21 Feb 2021. 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 Sweden. 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?

Event free survival (time frame: 1 year from transplantation). 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 NCT01025778, which also lists 5 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 21 Feb 2021.

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