SWOG clinical trial number

A Randomized Phase II/III Trial of "Novel Therapeutics" versus Azacitidine in Newly Diagnosed Patients with Acute Myeloid Leukemia Age 60 or Older

Abbreviated Title
Older AML
Status Notes
This study is temporarily closed to accrual, effective 10/22/18.

Research committees



Azacitidine Decitabine Midostaurin Cytarabine Nivolumab

Eligibility Criteria Expand/Collapse

Registration Step 1 - Specimen Submission
-Pts must be suspected to have previously untreated AML or MDS-EB-2.
-Pts must be >/= 60 years of age.
-Pts must not be known to have AML in the CNS.
-Pts must have specimens submitted for FLT3 testing for randomization stratification.
-Pts must be offered participation in specimen banking.
-Pts who have received prior therapy with midostaurin, any anti-PD-1 or anti-
PD-L1 therapy, any DNA-methyltransferase inhibitor for any condition, or prior intensive cytotoxic
therapy for MDS, are not eligible.
-Pts must be able to swallow oral medications without crushing or chewing.
-Prior malignancy is allowed providing it does not require concurrent therapy (active hormonal therapy is allowed).
-Pts must not be pregnant or nursing. Women/men of reproductive potential must have agreed to use an effective contraceptive method. Women must agree to avoid breast-feeding and WOCBP must agree to use highly effective contraception while receiving study drug and for a period of 31 weeks after the last dose of study drug. Sexually-active men must agree to use a condom while receiving study drug and for 31 weeks after the last dose of study drug. Vasectomized men must also agree to use a condom to avoid delivering drug in the seminal fluid.
-Pts must be informed of the investigational nature of this study and must sign and give written informed consent.

Registration Step 2 � Randomization
-Pts 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.
-Pts must have morphologically confirmed, previously untreated AML or MDS-EB-2.
-Pts with APL, biphenotypic leukemia, blastic transformation of CML or BCR/ABL, are not eligible.
-Pts must have disease present in the blood or bone marrow.
-Pts must not be known to have AML in the CNS.
-Pts must be deemed to be ineligible for intensive induction therapy, or must have refused intensive induction therapy.
-Pretreatment cytogenetics must be performed on all pts.
-E-mail notification that FLT3 specimens have been processed must be received prior to randomization.
-Prior treatment with hydroxyurea is permitted. Prior ATRA for suspected APL and prior intrathecal therapy are permitted, but must plan to be discontinued prior to initiating protocol therapy. Pts with signs/symptoms of hyperleukocytosis or WBC >/= 50,000/mcL can be treated with leukapheresis prior to randomization.
-Pts 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.
-Pts 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 to establish baseline values:
� Performance Status, � CBC/Differential/Platelets, � Creatinine Clearance (Cockcroft-Gault), � Total Bilirubin, � AST and ALT, � LDH, � Albumin, � Glucose, � Fibrinogen, � ECG �
-Pts must have complete history and physical examination within 28 days prior to randomization. History must include autoimmune disease status.
-Pts must not have active infection that is not controlled.
-Pts must be eligible for at least one of the currently active investigational treatment arms
-Pts must be informed of the investigational nature of this study and must sign and give written informed consent.

Treatment Arm Specific Eligibility Criteria for Active Treatment Arms

Arm B (Azacitidine + Nivolumab)
-Pts 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.
-Additional Arm-Specific Laboratory/Treatment Criteria:
� Pts must have AST and ALT </= 2.5 x IULN, � Pts must have total bilirubin </= 1.5 x IULN, � Pts must have baseline troponin test performed for eligibility;

Arm C (Azacitidine + Midostaurin)
- Additional Arm-Specific Laboratory/Treatment Criteria:
� Pts must have total bilirubin </= 2.5 x IULN, � Pts must have creatinine clearance </= 2.5 x IULN, � Pts must have QTc interval < 500/msec (by Bazett�s formula) on baseline ECG, � Pts must not have any history of hypersensitivity to any drugs or metabolites of midostaurin.

Publication Information Expand/Collapse


Accrual Barriers and Detection of Early Toxicity Signal in Older Less-Fit Patients Treated with Azacitidine and Nivolumab for Newly Diagnosed Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome (MDS) in the SWOG 1612 Platform Randomized Phase II/III Clinical Trial

A Hay;S Assouline;R Walter;RF Little;A Moseley;G Sperling;A Im;J Foran;J Radich;M Fang;HP Erba;L Michaelis American Society of Hematology Annual Meeting (Dec 7-10, 2019, Orlando, FL), poster


Intergroup LEAP trial (S1612): A randomized phase 2/3 platform trial to test novel therapeutics in medically less fit older adults with acute myeloid leukemia

RB Walter;LC Michaelis;M Othus;GL Uy;JP Radich;RF Little;RF Little;S Hita;L Saini;JM Foran;AT Gerds;HD Klepin;AE Hay;JE Lancet;S Couban;MR Litzow;RM Stone;HP Erba American Journal of Hematology Feb;93(2):E49-E52

PMid: PMID29164656 | PMC number: PMC5760282

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