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Acute Myeloid LeukemiaPhase 2BRIDGENCT01295307

Clofarabine Salvage Therapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)

A Phase 2 study testing Clofarabine in people with Acute Myeloid Leukemia, run by Technische Universität Dresden at 10 sites in Germany.

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

In relapsed or refractory AML allogeneic HCT is considered to be the only treatment by which long-term disease-free survival can be achieved. Despite this favorable prospect, even in younger patients with relapsed AML only about 40% of the patients reach allogeneic HCT. Read more about this study

Who is it for?
Ages 40 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
Clofarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
86 participants
Where
10 sitesGermany
Study dates
Mar 2011to Dec 2013
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 40 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of AML according to WHO criteria.
  • Untreated relapse or refractory disease after a minimum of one standard induction therapy. Treatment of relapse with leukocyte-apheresis or up to 5 days with low dose cytarabine or hydroxyurea is allowed.
  • Refractory disease is defined as ≥5% blasts after the second cycle of induction therapy or no reduction in marrow blasts at early treatment assessment (day +15) after the first cycle of induction therapy.
  • Relapse is defined as an increase in bone marrow blast count ≥5%, re-appearance of blasts in the peripheral blood or extramedullary disease.
  • Age above 40 years.
  • Have adequate renal and hepatic functions as indicated by the following laboratory values:
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  • Serum creatinine <=1.0 mg/dL; if serum creatinine >1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be >60 mL/min/1.73 m2 (see reference below*)
  • Serum bilirubin <=1.5× upper limit of normal (ULN)
  • Aspartate transaminase (AST)/alanine transaminase (ALT) <=2.5× ULN
  • Alkaline phosphatase <=2.5× ULN
  • Eligibility for intensive chemotherapy
  • Patient needs to be capable to understand the clinical trial as an investigational approach to bridge the time to potential allogeneic HCT, potential risks and benefits of the study.
  • Signed written informed consent.
  • Female patients of childbearing potential must have a negative serum
  • 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

  • For refractory disease, more than two prior induction chemotherapies or more than one prior salvage chemotherapy containing high-dose cytarabine (cumulative dose of cytarabine ≥ 5 g/m2).
  • Second or higher relapse. Patients who received hypomethylating agents like azacytidine or decitabine as a treatment of first relapse, respond and relapse later on may be included.
  • Acute promyelocytic leukemia with t(15;17)(q22;q12) molecular detection or (PML/RARα).
  • Central nervous system involvement (i.e. WBC ≥ 5/µL in cerebrospinal fluid with blasts present on cytospin).
  • Prior allogeneic HCT
  • Autologous transplantation within 100 days prior to start of study treatment
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  • Use of investigational agents or anticancer therapy within 10 days before study entry with the exception of hydroxyurea or low-dose cytarabine.
  • 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 transplantation.
  • Patients with known refractoriness to platelet support.
  • 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 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

10 sites in 1 country.

10 sites in 1 country

Germany10 sites

  • HELIOS Klinikum Bad Saarow

    Bad Saarow

  • Klinikum Chemnitz gGmbH

    Chemnitz

  • University Hospital Carl Gustav Carus

    Dresden, 01307

  • Universitätsklinikum Erlangen

    Erlangen

  • Klinikum der J. W. Goethe-Universität

    Frankfurt am Main

  • Klinikum Mannheim GmbH

    Mannheim

  • Universitätsklinikum Münster

    Münster

  • Klinikum Nürnberg Nord

    Nuremberg

  • Universitätsklinikum Tübingen

    Tübingen

  • Universitätsklinikum Würzburg

    Würzburg

Other trials in Germany

About this study

Official title: Clofarabine Salvage Therapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia

In relapsed or refractory AML allogeneic HCT is considered to be the only treatment by which long-term disease-free survival can be achieved. Despite this favorable prospect, even in younger patients with relapsed AML only about 40% of the patients reach allogeneic HCT. A number of factors contribute to this low rate of transplantation, among them moderate activity of the salvage regimens and accumulating toxicities which prevent from transplantation; Prospective clinical trials in this indication usually focus either on the rate of CR achieved after a defined number of cycles of salvage therapy or on transplantation modalities. The consequent integration of salvage therapy into a transplant strategy accounting for the time-dependent process of donor search has not been studied so far.

The objective of this study is to evaluate the safety and efficacy of clofarabine salvage therapy prior to allogeneic HCT.

Read the detailed description

All patients are scheduled for at least one cycle of induction therapy with CLARA. CLARA contains clofarabine 40 mg/m2 (1 hr infusion) days 1-5 followed 3 hours after the end of infusion by intermediate dose cytarabine 1 g/m2 (2 hrs infusion) days 1-5. Patients with moderate early response (reduced marrow blast count but ≥10% at day 15) or patients with progressive disease during delayed hematologic recovery (beyond day 42) may receive re-induction therapy similar to the first cycle induction therapy.

Study treatment comprises up to two cycles of induction therapy and one to two cycles of consolidation chemotherapy for patients without a donor. Consolidation therapy is reduced by 25% and consists of clofarabine 40 mg/m2 (1 hr infusion) days 1-4 followed 3 hours after the end of infusion by intermediate dose cytarabine 1 g/m2 (2 hrs infusion) days 1-4.

Patients for whom a donor can be identified may proceed to allogeneic HCT after CLARA I adopting the concept of allogeneic HCT in aplasia. Patients for whom donor search is more time consuming should proceed to allogeneic HCT once a donor has been identified.

Patients who have achieved a response after the last cycle of CLARA will receive clofarabine as part of the conditioning regimen. Clofarabine and melphalan may only be given as conditioning therapy to patients with HLA-compatible donors with a maximum of one mismatch refering to the HLA-loci A, -B, -C and -DRB1. Conditioning therapy then contains clofarabine 30 mg/m2 (1 hr IV infusion) days -6 to -3 and melphalan 140 mg/m2 (1 hour IV infusion) on day -2.

Being tested
Clofarabine
Keywords
acute myeloid leukemia, relapsed, refractory, Relapsed or refractory AML
Medical subject headings
Leukemia, Myeloid, Acute, Recurrence

What participants receive

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

  • ClofarabineDrug

    Induction and consolidation therapy / conditioning therapy with Clofarabine

Study groups in NCT01295307
Study groupRoleWhat they receive
Single ArmExperimentalInduction therapy with clofarabine/cytarabine. Post-remission therapy with either allogeneic HCT after conditioning with clofarabine/melphalan if a donor is available, or clofarabine/cytarabine if no donor is available
Receives: Drug: Clofarabine

What is being measured

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

  1. Rate of treatment success

    Treatment success is defined as a complete remission (CR, CRi or CRchim) at final response assessment after having completed the study treatment. CR and CRi are defined according to standard criteria (ELN). Complete remission by chimerism (CR chim) is defined as a >95% overall donor chimerism assessed by STR-PCR in bone marrow and absence of extramedullary disease together with an absolute neutrophil count >0.5 /nL (500/μL).

    Measured: To be evaluated 42 days after start of last cycle of chemotherapy containing clofarabine

Secondary outcomes (3)

  1. Rate of transplantation

    Rate of patients who finally proceeded to allogeneic HCT after bridging therapy with Clofarabine

    Measured: see evaluation of primary endpoint

  2. Adverse drug reactions

    Rate of adverse drug reactions.

    Measured: see evaluation of primary endpoint

  3. Treatment failure

    Cause specific analysis of treatment failure

    Measured: see evaluation of primary endpoint

Timeline

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

  1. First posted14 Feb 2011 (estimated)
  2. Study startMar 2011
  3. Primary completionSep 2013
  4. Study completionDec 2013

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
86 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01295307
Sponsor's protocol ID
TUD-BRIDGE-046
Other IDs
2010-022584-35
Acronym
BRIDGE
Status last verified
Oct 2015
First submitted
4 Feb 2011
Last updated
7 Oct 2015
Results posted
No

Publications

  • Middeke JM, Herbst R, Parmentier S, Bug G, Hanel M, Stuhler G, Schafer-Eckart K, Rosler W, Klein S, Bethge W, Bitz U, Buttner B, Knoth H, Alakel N, Schaich M, Morgner A, Kramer M, Sockel K, von Bonin M, Stolzel F, Platzbecker U, Rollig C, Thiede C, Ehninger G, Bornhauser M, Schetelig J. Clofarabine salvage therapy before allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory AML: results of the BRIDGE trial. Leukemia. 2016 Feb;30(2):261-7. doi: 10.1038/leu.2015.226. Epub 2015 Aug 18.

    PubMed 26283567

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Clofarabine in people with Acute Myeloid Leukemia, run by Technische Universität Dresden at 10 sites in Germany.

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 15 inclusion and 12 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 7 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Germany. 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?

Rate of treatment success (time frame: To be evaluated 42 days after start of last cycle of chemotherapy containing clofarabine). 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 NCT01295307, which also lists 1 linked publication.

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 7 Oct 2015.

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