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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01883362
First received: March 25, 2013
Last updated: September 10, 2014
Last verified: September 2014
  Purpose

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,


Condition Intervention Phase
Acute Myeloid Leukemia
Drug: Midostaurin (PKC412)
Other: Standard of Care
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase II, Randomized, Comparative Trial of Standard of Care, With or Without Midostaruin to Prevent Relapse Following Allogeneic Hematopoietic Stem Cell Transplantation in Patients With FLT3-ITD Mutated Acute Myeloid Leukemia

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Relapse Free Survival (RFS) [ Time Frame: 18 months from date of transplant ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Disease Free Survival (DFS) [ Time Frame: for at least 24 months from date of transplant or study completion ] [ Designated as safety issue: No ]
  • Non-Relapse Mortality (NRM) [ Time Frame: for at least 24 months from date of transplant or study completion ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: for at least 24 months from date of transplant or study completion ] [ Designated as safety issue: No ]
  • FLT3-ITD mutation status centrally in archived material from diagnosis (if available) including mutant:wild type ratio [ Time Frame: upto 24 months from date of transplannt or at study completion ] [ Designated as safety issue: No ]
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    The assessment of safety will be based mainly on the frequency of Adverse Events (AEs), on the number of laboratory values summarized by CTCAE grades and non-relapse mortality(NRM). The assessment of tolerability will be based on whether midostaurin can be administered at a daily dose of 50mg twice daily at least 80% of the time to 50% or more of patients during the first 100 days after allogeneic HSCT

  • Plasma Pharmacokinetics (PK) of midostaurin and the metabolites: CGP62221 and CGP52421: Pre-dose levels [ Time Frame: Pre-dose on days 1 and 15 of Cycle 1, on day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 ] [ Designated as safety issue: Yes ]
    Pre-dose levels (Cmin) will be directly determined from raw plasma concentration-time data (units ng/ml)

  • Plasma Pharmacokinetics (PK) of midostaurin and the metabolites: CGP62221 and CGP52421: Pre-dose levels [ Time Frame: Pre-dose collection two weeks following initiation of strong CYP3A4 inhibitors ] [ Designated as safety issue: Yes ]
    Pre-dose levels (Cmin) will be directly determined from raw plasma concentration-time data (units ng/ml)


Estimated Enrollment: 60
Study Start Date: October 2014
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Standard of Care (SOC) with Midostaurin
Patients will receive standard of care in the post SCT setting in addition to Midostaurin 50mg twice a day for 12 months (cycles).
Drug: Midostaurin (PKC412)
Midostaurin (PKC412) 50mg twice a day for 28 days of each cycle. Patients will be treated for 12 cycles.
Other Name: PKC412, Midostaurin
Active Comparator: Standard of Care (SOC)
Patients will receive standard of care alone in the post SCT setting
Other: Standard of Care
Standard of Care is not defined per protocol. The investigator will prescribe based on the commonly used medications given in the post SCT setting.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must be between 18 and 60 years of age
  • Patients must have an ECOG Performance Status of < 2
  • Patients must have a documented Unequivocal diagnosis of AML according to WHO 2008 classification (>20% blasts in the bone marrow), excluding M3 (acute promyelocytic leukemia).
  • Patients must have a documented FLT3 ITD mutation, determined by local laboratory for eligibility (historical tissue will be requested for central analysis confirmation)
  • Patients who have undergone allogeneic HSCT in CR1 from a matched related or matched unrelated donor. All of the following criteria must also 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 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 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 whom have failed prior attempts at allogeneic HSCT
  • Patients who have 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 are 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 requires 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 use highly effective methods of contraception during dosing and for 30 days after treatment completion

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01883362

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

  Show 24 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Jodi Virkus, Pharm D Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01883362     History of Changes
Other Study ID Numbers: CPKC412AUS23
Study First Received: March 25, 2013
Last Updated: September 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
acute myeloid leukemia
AML
FLT3-ITD
midostaurin
PKC412
allogeneic hematopoeitic stem cell tranplant
SCT
HSCT
CR1

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia
Neoplasms by Histologic Type
Neoplasms
4'-N-benzoylstaurosporine
Staurosporine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014