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

NCT01295307 | Completed Phase 2

• 2 other identifiers: TUD-BRIDGE-0462010-022584-35
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 10

Brief 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. 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.

Conditions

Acute Myeloid Leukemia

Keywords

acute myeloid leukemia; relapsed; refractory; Relapsed or refractory AML

Outcome Measures

Primary Outcomes (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).

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

Secondary Outcomes (3)

• Rate of transplantation

  see evaluation of primary endpoint

• Adverse drug reactions

  see evaluation of primary endpoint

• Treatment failure

  see evaluation of primary endpoint

Study Arms (1)

Single Arm

EXPERIMENTAL

Induction 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

Drug: Clofarabine

Interventions

Clofarabine DRUG

Induction and consolidation therapy / conditioning therapy with Clofarabine

Single Arm

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Technische Universität Dresden: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (10)

HELIOS Klinikum Bad Saarow

Bad Saarow, Germany

Location

Klinikum Chemnitz gGmbH

Chemnitz, Germany

Location

University Hospital Carl Gustav Carus

Dresden, 01307, Germany

Location

Universitätsklinikum Erlangen

Erlangen, Germany

Location

Klinikum der J. W. Goethe-Universität

Frankfurt am Main, Germany

Location

Klinikum Mannheim GmbH

Mannheim, Germany

Location

Universitätsklinikum Münster

Münster, Germany

Location

Klinikum Nürnberg Nord

Nuremberg, Germany

Location

Universitätsklinikum Tübingen

Tübingen, Germany

Location

Universitätsklinikum Würzburg

Würzburg, Germany

Location

Related Publications (1)

• 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.

  PMID: 26283567 RESULT

Related Links

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MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence

Interventions

Clofarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides

Study Officials

• Johannes Schetelig, MD

  Universitätsklinikum Dresden, Med. Klinik und Poliklinik I, Study Alliance Leukemia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PD Dr. med. Johannes Schetelig

Study Record Dates

• First Submitted: February 4, 2011
• First Posted: February 14, 2011
• Study Start: March 1, 2011
• Primary Completion: September 1, 2013
• Study Completion: December 1, 2013
• Last Updated: October 7, 2015

Record last verified: 2015-10

Locations

DE (10)