Impact of Remission Induction Chemotherapy Prior to Allogeneic SCT in Relapsed and Poor-response Patients With AML

• Status: Recruiting
• Trial end date: 2023-05-01
• Target enrollment: 0
• Participant gender: All

Summary

This trial compares outcome of two treatment strategies for patients with high-risk AML who failed to achieve or maintain a complete remission with standard therapy. Patients will be randomized between two strategies. The standard strategy is aimed at achieving a complete remission by aggressive salvage chemotherapy using high dose cytarabine and mitoxantrone, . The alternative is a less toxic disease-control strategy of disease monitoring and, if necessary, low-dose cytarabine or mitoxantrone prior to allogeneic transplantation, which should be performed as soon as possible.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: DKMS gemeinnützige GmbH
• Treatments: Cytarabine; Mitoxantrone

Criteria

Inclusion Criteria

• Signed written informed consent.

• Male and female patients of 18 to 75 years of age.

• Diagnosis of AML according to WHO criteria.

• Patient is fit for aggressive induction chemotherapy and transplantation by assessment of an experienced hematologist.

• No history of chronic pulmonary disease and absence of dyspnea. Otherwise, documented diffusion lung capacity for carbon monoxide ( DLCO ) ≤ 40 percent ( adjusted for hemoglobin, if available ) and FEV1 / FVC ≥ 50 percent.

• HLA - identical sibling. or

• HLA - compatible unrelated donor ( ≥ 9 /10 antigens matched for HLA - A, - B, - C, -DRB 1, and - DQB 1 ) with completed confirmatory typing or

• Two unrelated donors with > 90 percent probability of a 9 /10 match for HLA - A, - B,
• C, - DRB 1, and - DRQB 1, according to Opti Match ® list.

For the relapse stratum

• First AML relapse, defined as ≥ 5 percent bone marrow blasts and / or extramedullary AML manifestation.

For the poor - responders stratum

• AML that evolves from previously documented myelodysplastic syndrome ( MDS ),

and / or

• diagnosis of therapy-related myeloid neoplasm ( t - MN ), and / or

a ) If patient ≤ 60 years old adverse risk AML according to ELN - criteria and ≥ 5 percent bone marrow blasts after the first cycle of induction therapy.

b ) If patient > 60 years old non-favourable risk AML according to ELN - criteria and ≥ 5 percent bone marrow blasts after the first cycle of induction therapy.

Exclusion Criteria

• Acute promyelocytic leukemia ( APL ).

• WBC count of ≥ 50 GPt / L at study inclusion.

• For patients in the poor - responder stratum the first cycle of induction therapy must not contain HDAC, defined as cytarabine at single-doses of > 1 g / m 2.

• Patient has received more than 440 mg / m2 daunorubicin equivalents.

• Severe organ dysfunction, defined as

• Left ventricular ejection fraction < 50 percent.

• Patients who receive supplementary continuous oxygen.

• Serum bilirubin > 1.5 x ULN ( if not considered Gilbert-Syndrome ), ASAT / ALAT > 5 x ULN.

• Estimated GFR < 50 ml / min.

• Treatment with any investigational drug within 10 days before study entry.

• Uncontrolled infection at the time of enrollment.

• History of allogeneic transplantation.

• Manifestation of AML in the central nervous system.

• Pregnant or breast - feeding women.

• Men unable or unwilling to use adequate contraception methods from start of study treatment to minimum of six months after the last dose of chemotherapy.

• Women of childbearing potential except those who fulfill the following criteria:

Post-menopausal or post-operative or continuous and correct application of a contraception method with a Pearl Index < 1 percent or sexual abstinence or vasectomy of the sexual partner.