NCI Community Oncology Research Program - Kansas City (NCORP-KC)
NCI Community Oncology Research Program - Kansas City (NCORP-KC)




NCI Community Oncology Research Program - Protocol Summary

SWOG S1612 - "A Randomized Phase II/III Trial of "Novel Therapeutics" Versus Azacitidine in Newly Diagnosed Patients With Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome (MDS), Age 60 or Older"

The summary below serves as a brief review of the treatment plan and eligibility for the protocol.


This summary is not intended to be used in place of the full eligibility & treatment information in the protocol.
 

Please contact NCORP-KC for complete protocol information.



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Leukemia Clinical Trial

CANCER TYPE: Acute
RESEARCH BASE: SWOG
NCT NUMBER: NCT03092674
HIPPA FORM: DOWNLOAD HIPPA FORM

Consent Form: VIEW CONSENT FORM
UPDATED ON 09/26/2018 (20:49:40)

Additional Consent Form: VIEW CONSENT FORM 2
UPDATED ON 09/26/2018 (20:49:40)

BRIEF DESCRIPTION

Untreated AML or MDS with excess blasts,  ≥ 60 years of age, FLT3 testing, Azacitidine vs. Azacitidine + Nivolumab vs. Azacitidine + Midostaurin vs. Decitabine + Cytarabine



NOTES


Treatment

Arm A:

Azacitidine 75mg/m2/day, SC or IV, days 1-7

Cycle = 28 days

Arm B:

Azacitidine 75mg/m2/day, SC or IV, days 1-7  AND

Nivolumab 3mg/kg, IV, days 1 and 15

Cycle = 28 days

Arm C:

Azacitidine 75mg/m2/day, SC or IV, days 1-7  AND

Midostaurin 50mg, twice daily, Orally, days 8-21

Cycle = 28 days

Arm D:

Induction (2 cycles):

Decitabine 20mg/m2/day, IV, days 1-5   AND

Cytarabine 100mg/m2, IV, days 6-11

Maintenance:

Decitabine 20mg/m2/day, IV, days 1-5

Cycle = 28 days

 



ELIGIBILITY

Step 1

  • Patients must be suspected to have previously untreated acute myelogenous leukemia (AML) or myelodysplastic syndrome with excess blasts-2 (MDS-EB-2).
  • Patients must be ≥ 60 years of age.
  • Patients must not be known to have AML in the CNS.
  • Patients must have specimens submitted for FLT3 testing for randomization stratification. Collection of pretreatment specimens must be completed within 1 day of registration to Step 1. Specimens must be submitted via the SWOG Specimen Tracking System as outlined in Section 15.2. FLT3 results will be used for stratification purposes at the time of randomization. E-mail notification of randomization assignment must be received prior to Step 2 registration.
  • Patients must be offered participation in specimen banking as outlined in Section 15.3. With patient consent, pretreatment specimens must be collected and submitted via the SWOG Specimen Tracking System as outlined in Section 15.3.
  • Patients who have received prior therapy with midostaurin, any anti-PD-1 or antiPD-L1 therapy, any DNA-methyltransferase inhibitor (including hypomethylating agents such as azacitidine, decitabine, or other investigational agent that acts by inhibiting DNA or RNA methylation) for any condition, or prior intensive cytotoxic therapy for MDS, are not eligible.
  • Patients must be able to swallow oral medications without crushing or chewing.
  • Prior malignancy is allowed providing it does not require concurrent therapy. Exception: Active hormonal therapy is allowed.
  • Patients must not be pregnant or nursing.

Step 2

  • Patients must be registered to Step 2 no more than 42 days after registration to Step 1 and no more than 42 days after collection of specimens for FLT3 testing.
  • Patients must have morphologically confirmed, previously untreated acute myeloid leukemia (AML) or MDS with excess blasts-2 (MDS-EB-2). 
  • Patients must have disease present in the blood or bone marrow; patients with only extramedullary disease in the absence of bone marrow or blood involvement are not eligible.
  • All tests for establishing baseline disease status eligibility must be based on blood and/or bone marrow examination performed within 42 days prior to randomization (registration Step 2).
  • Patients must not be known to have AML in the CNS.
  • Patients must be deemed, in the judgment of the treating physician, to be ineligible for intensive induction therapy, or must have refused intensive induction therapy. Rationale for clinical determination or notation of patient decision must be made on the S1612 Onstudy Form.
  • Pretreatment cytogenetics must be performed on all patients as outlined in Section 15.4. Collection of pretreatment specimens must be completed within 42 days prior to randomization (registration Step 2). Reports of the results must be submitted as outlined in Sections 14.4 and 15.4.
  • FLT3 results will be used for stratification purposes at the time of randomization. E-mail notification that FLT3 specimens have been processed must be received prior to randomization (registration Step 2).
  • Prior treatment with hydroxyurea is permitted (see Section 7.2 for information regarding use of hydroxyurea while on protocol therapy). Prior ATRA for suspected APL and prior intrathecal therapy are permitted, but must plan to be discontinued prior to initiating protocol therapy. Patients with signs/symptoms of hyperleukocytosis or WBC ≥ 50,000/mcL can be treated with leukapheresis prior to randomization (registration to Step 2).
  • Patients may have received non-intensive therapy for antecedent hematologic disorders, including lenalidomide. Patients may have received prior chemotherapy for prior cancers. These therapies must be discontinued at least 5 days prior to randomization (registration to Step 2).
  • Patients who are transfusion-dependent and patients receiving growth factor support are eligible. Patients must discontinue growth factor support prior to initiation of protocol therapy.
  • The following tests must be performed within 14 days prior to randomization (registration to Step 2) to establish baseline values:
    • Performance Status
    • CBC/Differential/Platelets
    • Creatinine Clearance (Cockcroft-Gault)*
    • Total Bilirubin
    • AST and ALT
    • LDH
    • Albumin
    • Glucose
    • Fibrinogen
    • ECG (see Section 5.3b, Arm C)
  • Patients must have complete history and physical examination within 28 days prior to randomization (registration to Step 2). History must include autoimmune disease status (to determine whether patient is eligible for Arm B, see Section 5.3a).
  • Patients must not have active infection (systemic bacterial, fungal, or viral infection) that is not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement despite appropriate antibiotics or other treatment).
  • Patients must be eligible for at least one of the currently active investigational treatment arms (S1612B or S1612C). If the patient does not meet eligibility criteria for at least one active investigational arm, then the patient is not eligible for S1612.
  • Arm B Eligibility
    • Patients must not have active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
    • Patients must have AST and ALT ≤ 2.5 x IULN.
    • Patients must have total bilirubin ≤ 1.5 x IULN.
    • Patients must have baseline troponin test performed for eligibility; however, no associated values must be met in order for the patient to be eligible.
  • Arm C Eligibility
    • Patients must have total bilirubin ≤ 2.5 x IULN.
    • Patients must have creatinine clearance ≤ 2.5 x IULN.
    • Patients must have QTc interval < 500/msec (by Bazett’s formula) on baseline ECG.
    • Patients must not have any history of hypersensitivity to any drugs or metabolites of midostaurin.
  • All tests for establishing baseline values must be completed within 14 days prior to registration to Step 2 (randomization).





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