Early Allogeneic Blood Stem Cell Transplantation in High-risk Acute Myeloid Leukemia (AML)

NCT00188136 | Completed Phase 2

• 1 other identifier: DDEATX
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Karyotype is a major prognostic risk factor in patients with acute myeloid leukemia (AML) translating into unfavourable outcome in case of poor-risk cytogenetic aberrations. Several studies have shown that allogeneic hematopoietic stem cell transplantation (HSCT) after myeloablative conditioning rather than autologous HSCT or consolidation chemotherapy result in long-term disease control in this group of patients when achieving a first complete remission. Nevertheless, the complete remission rate achievable is significantly lower than in patients with a more favourable risk profile. In fact, only the minority of AML patients with poor-risk cytogenetics, although having a suitable donor, proceed to HSCT due to refractory disease or infectious complications during induction chemotherapy (IC). Further, new data show that the course of therapy can be estimated as early as two weeks after the initiation of the first course of IC with patients presenting with more than 10 % marrow blasts doing significantly worse than those with a better clearance of blasts. As a result, the chance to obtain a durable remission is considerably low and most patients with bad-risk cytogenetics or failure to achieve blast clearance do not proceed to an allogeneic approach. Together these data indicate that early treatment intensification is warranted in order to provide the potential curative benefit of allogeneic HSCT to the majority of high-risk AML patients. We have shown that reduced-intensity conditioning (RIC) followed by allogeneic PBSC applied during aplasia after the first cycle of IC in newly-diagnosed high-risk AML patients is feasible and can result in a sustained disease control. These data prompted us to further evaluate in a prospective trial an early "up-front HSCT" in patients with newly-diagnosed high-risk AML defined by karyotype and insufficient blast clearance after the first cycle of IC. The goal was to provide an allogeneic HSCT as early as possible after diagnosis in AML patients.

Conditions

Acute Myeloid Leukemia

Keywords

AML, allogeneic transplantation, high-risk, karyotype

Outcome Measures

Primary Outcomes (1)

• Total and relapse-free survival rate one year after the stem cell transplantation

  5 years

Secondary Outcomes (2)

• Incidence of acute GvHD

  100 days

• Safety (evaluated after Common Terminology Criteria for Adverse Events [CTCAE] v 3.0)

  5 years

Interventions

Melphalan, ATG, Fludarabine DRUG

allo Tx during aplasia

Eligibility Criteria

• Age: 16 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• newly-diagnosed AML
• either poor risk cytogenetics and/or bad response to the first cycle of IC defined by more than 10% marrow blasts on day 15
• HLA-compatible donor (maximum one HLA-antigen mismatch)

You may not qualify if:

• no donor
• Age \< 16 years \> 75 years
• Cardiac insufficiency requiring treatment or symptomatic coronary artery disease
• Hepatic disease, with AST \> 2 times normal
• Severe hypoxemia , pO2 \< 70 mm Hg, with decreased DLCO \< 70% of predicted; or mild hypoxemia, pO2 \< 80 mm Hg with severely decreased DLCO \< 60% of predicted
• Impaired renal function (creatinine \> 2 times normal or creatinine clearance \< 50% for age, weight, height)
• HIV-positive patients due to risk of reactivation or acceleration of HIV replication
• Female patients who are pregnant or breast feeding due to risks to fetus from conditioning regimen and potential risks to nursing infants
• Life expectancy severely limited by diseases other than malignancy

Sponsors & Collaborators

• University Hospital Carl Gustav Carus: lead

Study Sites (1)

University hospital Carl Gustav Carus

Dresden, 01307, Germany

Location

Related Publications (1)

• Platzbecker U, Thiede C, Freiberg-Richter J, Rollig C, Helwig A, Schakel U, Mohr B, Schaich M, Ehninger G, Bornhauser M. Early allogeneic blood stem cell transplantation after modified conditioning therapy during marrow aplasia: stable remission in high-risk acute myeloid leukemia. Bone Marrow Transplant. 2001 Mar;27(5):543-6. doi: 10.1038/sj.bmt.1702819.

  PMID: 11313690 RESULT

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Melphalan; fludarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Martin Bornhauser, Prof

  University hospital Carl Gustav Carus Dresden

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 16, 2005
• Study Start: August 1, 2002
• Primary Completion: July 1, 2010
• Study Completion: December 1, 2010
• Last Updated: December 8, 2015

Record last verified: 2015-12

Locations

DE (1)