NCT03092674|CompletedPhase 2ResultsFDA Drug

Azacitidine With or Without Nivolumab or Midostaurin, or Decitabine and Cytarabine Alone in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

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 LEAP: Less-Intense AML Platform Trial

National Cancer Institute (NCI)ClinicalTrials.gov

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3 other identifiers

NCI-2017-00436S1612U10CA180888

Study Type

interventional

Target

Locations

1 country

Sites

506

Timeline

RegisteredMar 2017

StartedFeb 2018

CompletionJun 2024

Brief Summary

This randomized phase II/III trial studies how well azacitidine with or without nivolumab or midostaurin, or decitabine and cytarabine alone work in treating older patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Drugs used in chemotherapy, such as azacitidine, decitabine, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Midostaurin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving azacitidine with or without nivolumab or midostaurin, or decitabine and cytarabine alone may kill more cancer cells.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P50-P75 for phase_2

Timeline

Completed

Started Feb 2018

Longer than P75 for phase_2

Geographic Reach

1 country

506 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

6.4 years study duration

First Submitted

Initial submission to the registry

March 23, 2017

Completed

5 days until next milestone

First Posted

Study publicly available on registry

March 28, 2017

Completed

10 months until next milestone

Study Start

First participant enrolled

February 2, 2018

Completed

5.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2023

Completed

11 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 26, 2024

Completed

27 days until next milestone

Results Posted

Study results publicly available

July 23, 2024

Completed

Last Updated

January 16, 2025

Status Verified

December 1, 2024

Enrollment Period

5.5 years

First QC Date

March 23, 2017

Results QC Date

June 5, 2024

Last Update Submit

January 15, 2025

Conditions

Acute Myeloid Leukemia Myelodysplastic Syndrome Myelodysplastic Syndrome/Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

Overall Survival (OS) (Phase II)
Time from date of randomization on study until death from any cause with observations censored on the day of last contact for patients not known to have died.
Day of registration on study until death from any cause, assessed for up to 5 years
OS (Phase III)
Time from date of randomization on study until death from any cause with observations censored on the day of last contact for patients not known to have died.
Day of registration on study until death from any cause, assessed for up to 5 years

Secondary Outcomes (1)

Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Duration of treatment and follow up until death or 5 years post randomization (registration to Step 2).

Other Outcomes (8)

Remission Rates
Up to 5 years
OS
Day of registration on study until death from any cause, assessed for up to 5 years
Relapse-free Survival (RFS)
Date of achievement of a remission until the date of relapse or death from any cause, assessed for up to 5 years
+5 more other outcomes

Study Arms (4)

Arm A (azacitidine)

ACTIVE COMPARATOR

Patients receive azacitidine SC or IV daily on days 1-7 or on an interrupted schedule which ensures that all 7 days of therapy are received within a 12 day period. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: AzacitidineOther: Laboratory Biomarker Analysis

Arm B (azacitidine, nivolumab)

EXPERIMENTAL

Patients receive azacitidine as in Arm A and nivolumab IV over 30-60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: AzacitidineOther: Laboratory Biomarker AnalysisBiological: Nivolumab

Arm C (azacitidine, midostaurin)

EXPERIMENTAL

Patients receive azacitidine as in Arm A and midostaurin orally (PO) twice daily (BID) on days 8-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: AzacitidineOther: Laboratory Biomarker AnalysisDrug: Midostaurin

Arm D (decitabine, cytarabine)

EXPERIMENTAL

INDUCTION: Patients receive decitabine IV over 2 hours on days 1-5 and cytarabine IV continuously on days 6-11. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients deemed stable at the discretion of the treating physician receive decitabine as in Induction. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: CytarabineDrug: DecitabineOther: Laboratory Biomarker Analysis

Interventions

AzacitidineDRUG

Given SC or IV

Also known as: 5 AZC, 5-AC, 5-Azacitidine, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza

Arm A (azacitidine)Arm B (azacitidine, nivolumab)Arm C (azacitidine, midostaurin)

CytarabineDRUG

Given IV

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Arm D (decitabine, cytarabine)

DecitabineDRUG

Given IV

Also known as: 5-Aza-2'-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine

Arm D (decitabine, cytarabine)

Laboratory Biomarker AnalysisOTHER

Correlative studies

Arm A (azacitidine)Arm B (azacitidine, nivolumab)Arm C (azacitidine, midostaurin)Arm D (decitabine, cytarabine)

MidostaurinDRUG

Given PO

Also known as: CGP 41251, CGP41251, N-Benzoyl-Staurosporine, N-Benzoylstaurosporine, PKC 412, PKC-412, PKC412, Rydapt

Arm C (azacitidine, midostaurin)

NivolumabBIOLOGICAL

Given IV

Also known as: ABP 206, BCD-263, BMS 936558, BMS-936558, BMS936558, CMAB819, MDX 1106, MDX-1106, MDX1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar BCD-263, Nivolumab Biosimilar CMAB819, ONO 4538, ONO-4538, ONO4538, Opdivo

Arm B (azacitidine, nivolumab)

Eligibility Criteria

Age60 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

REGISTRATION STEP 1-SPECIMEN SUBMISSION
Patients must be suspected to have previously untreated acute myelogenous leukemia (AML) or myelodysplastic syndrome with excess blasts-2 (MDS-EB-2)
Patients must not be known to have AML in the central nervous system (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 Southwest Oncology Group (SWOG) Specimen Tracking System; 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; with patient consent, pretreatment specimens must be collected and submitted via the SWOG Specimen Tracking System
Patients who have received prior therapy with midostaurin, any anti-PD-1 or anti-PD-L1 therapy, any deoxyribonucleic acid (DNA)-methyltransferase inhibitor (including hypomethylating agents such as azacitidine, decitabine, or other investigational agent that acts by inhibiting DNA or ribonucleic acid \[RNA\] methylation) for any condition, or prior intensive cytotoxic therapy for myelodysplastic syndrome (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; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception also includes (but is not limited to) heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy, bilateral tubal ligation, or vasectomy; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
Women must agree to avoid breast-feeding and women of child-bearing potential (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
Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
REGISTRATION STEP 2-RANDOMIZATION: 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
REGISTRATION STEP 2-RANDOMIZATION: Patients must have morphologically confirmed, previously untreated acute myeloid leukemia (AML) or MDS with excess blasts-2 (MDS-EB-2)
+36 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

National Cancer Institute (NCI)lead

Study Sites (506)

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Alaska Breast Care and Surgery LLC