Standard of Care +/- Midostaurin to Prevent Relapse Post Stem Cell Transplant in Patients With FLT3-ITD Mutated AML (RADIUS)

Novartis

Status and phase: Completed; Phase 2

Conditions: Acute Myeloid Leukemia

Treatments: Other: Standard of Care; Drug: Midostaurin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01883362

CPKC412AUS23

Details and patient eligibility

About

To determine if the addition of midostaurin (PKC412) to Standard of Care (SOC) therapy reduces relapse in FLT3-ITD mutated AML patients receiving an allogenetic hematopoietic stem cell transplant,

Enrollment: 60 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients between 18 and 70 years of age
• Patients with ECOG Performance Status of ≤ 2
• Patients with a documented unequivocal diagnosis of AML according to WHO 2008 classification (>20% blasts in the bone marrow), excluding M3 (acute promyelocytic leukemia).
• Patients with a documented FLT3 ITD mutation, determined by local laboratory for eligibility (historical tissue will be requested for central analysis confirmation)
• Patients who undersent allogeneic HSCT in CR1 from a matched related or matched unrelated donor. All of the following criteria had to be met: HLA typing to include available 8/8 or 7/8 allele HLA matched donor (at A,B,C, DRB1) Single allelic mismatch allowed
• Patients who had received a conditioning regimen which included one of the following:

Busulfan/Fludarabine (Bu/Flu) Busulfan (16 mg/kg PO or 12.8 mg/kg IV) Fludarabine (120-180 mg/m2) Fludarabine / Melphalan (Flu/Mel) Fludarabine (120-180 mg/m2) Melphalan (≤ 150 mg/m2) Busulfan/Cyclophosphamide (Bu/Cy) Busulfan (16 mg/kg PO or 12.8 mg/kg IV) Cyclophosphamide (120 mg/kg) Cyclophosphamide/Total Body Irradiation (Cy/TBI) Cyclophosphamide (120 mg/kg) TBI (1200-1420 cGy)

• Recovery of counts by day 42 and was able to start midostaurin by day 60 post-HSCT (first dose of midostaurin to start no earlier than 28 days post-HSCT); ANC >1000µL, platelets ≥20,000 without platelet transfusion

Exclusion criteria

Patients eligible for this study must not have met any of the following criteria:

• Patients who failed prior attempts at allogeneic HSCT

• Patients who had received an autologous transplant

• Patients with Acute GVHD Grade III-IV

• Patients with a known confirmed diagnosis of HIV infection or active viral hepatitis.

• Impaired cardiac function including any of the following:

  • Screening ECG with a QTc > 450 msec. If QTc > 450 and electrolytes were not within normal ranges, electrolytes should be corrected and then the patient rescreened for QTc.
  • Patients with congenital long QT syndrome
  • History or presence of sustained ventricular tachycardia
  • Any history of ventricular fibrillation or torsades de pointes
  • Bradycardia defined as HR. < 50 bpm
  • Right bundle branch block + left anterior hemiblock (bifascicular block)
  • Patients with myocardial infarction or unstable angina < 6 months prior to starting study
  • Congestive Heart Failure NY Heart Association class III or IV
  • Patients with an ejection fraction < 45% assessed by MUGA or ---ECHO within 28 days prior to starting study cycle 1 (of midostaurin or control group)

• Patients with any pulmonary infiltrate including those suspected to be of infectious origin (unless resolves to ≤ Grade 1 within screening timeframe)

• Patient required treatment with strong CYP3A4 inhibitors or moderate or strong CYP3A4 inducers other than those required for GVH or infection prophylaxis or treatment

Pregnant or nursing (lactating) women, or women of child-bearing potential, must have used highly effective methods of contraception during dosing and for 30 days after treatment completion

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

Standard of Care with Midostaurin

Experimental group

Description:

Patients received standard of care in the post stem cell transplant (SCT) setting in addition to Midostaurin 50mg twice a day for 12 months (cycles).

Treatment:

Drug: Midostaurin

Standard of Care

Active Comparator group

Description:

Patients received standard of care alone in the post SCT setting

Treatment:

Other: Standard of Care