Clinical trial for Previously Untreated Relapsed Refractory Acute Myeloid Leukemia
Official title Study of Biomarker-Based Treatment of Acute Myeloid Leukemia
ClinicalTrials.gov ID: NCT03013998
What this study is testing
What is Samalizumab (BAML-16-001-S1)?
Samalizumab (BAML-16-001-S1) is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for previously untreated relapsed refractory acute myeloid leukemia.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This screening and multi-sub-study Phase 1b/2 trial will establish a method for genomic screening followed by assigning and accruing simultaneously to a multi-study "Master Protocol (BAML-16-001-M1)." The specific subtype of acute myeloid leukemia will determine which sub-study, within this protocol, a participant will be assigned to evaluate investigational therapies or combinations with the ultimate goal of advancing new targeted therapies for approval. The study also includes a marker negative sub-study which will include all screened patients not eligible for any of the biomarker-driven sub-studies.
- Phase 3: a large, late-stage study
- Which group you join is decided by chance.
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- (IC):
- Adults, age ≥60 yrs at diagnosis unless in a specific known cytogenetic \& genomic group for which treatment in Group A, B, or C is allowed by the...
- Patients must be able to understand \& provide written informed consent
- Group A: Patients must have previously untreated AML according to WHO classification w/ no prior treatment other than hydroxyurea. Patients w/...
- Group B: Patients must have relapsed or refractory AML according to WHO classification. For study purposes, refractory AML is defined as failure to...
You likely can't join if
- (EC):
- Acute promyelocytic leukemia (APL)
- Clinically active CNS involvement by AML. A patient may be considered eligible if CNS leukemia is showing response to treatment at study entry \&...
- Signs of leukostasis requiring urgent therapy
- Disseminated intravascular coagulopathy (DIC) w/ active bleeding or signs of thrombosis
- Patients w/ psychological, familial, social, or geographic factors that otherwise preclude them from giving informed consent, following the protocol...
See the full eligibility criteria
Who can join
- (IC):
- Adults, age ≥60 yrs at diagnosis unless in a specific known cytogenetic \& genomic group for which treatment in Group A, B, or C is allowed by the substudy where age 18+ is allowed. Patients \<60 yrs who are screened...
- Patients must be able to understand \& provide written informed consent
- Group A: Patients must have previously untreated AML according to WHO classification w/ no prior treatment other than hydroxyurea. Patients w/ myeloid malignancies [eg, myelodysplastic syndrome (MDS) or other disease]...
- Group B: Patients must have relapsed or refractory AML according to WHO classification. For study purposes, refractory AML is defined as failure to ever achieve a complete response (CR) or recurrence of AML w/in 6...
- Group C: For select sites not part of Beat AML core sites. These sites will only participate in select substudies. Patients in this group will enroll under the Beat AML M1 MP w/ the intent to enroll into these select...
What rules you out
- (EC):
- Acute promyelocytic leukemia (APL)
- Clinically active CNS involvement by AML. A patient may be considered eligible if CNS leukemia is showing response to treatment at study entry \& should continue to receive intrathecal therapy as clinical indicated...
- Signs of leukostasis requiring urgent therapy
- Disseminated intravascular coagulopathy (DIC) w/ active bleeding or signs of thrombosis
- Patients w/ psychological, familial, social, or geographic factors that otherwise preclude them from giving informed consent, following the protocol (including failure to collect genomics samples for screening), or...
- Any other significant medical condition, including psychiatric illness or lab abnormality, that would preclude patient participation in the trial or would confound interpretation of trial results S17 - IC
- Age ≥60 yrs at diagnosis w/ untreated AML according to International Consensus Classification (ICC) 2022 \& have NPM1 mutated or KMT2A rearrangement disease \& are not candidates for or do not wish to pursue intensive...
- Patients must be able to understand \& provide written informed consent
- Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2
- Aspartate aminotransferase (AST) \<5 x upper limit of normal (ULN), alanine aminotransferase (ALT) \<5 x ULN, \& total bilirubin \<2 x ULN (except for patients w/ known or suspected Gilbert's syndrome \& w/ direct...
- Adequate renal function as defined by calculated creatinine clearance ≥60 mL/min for the local lab
- Females must be non-childbearing, postmenopausal, surgically sterile or meet certain criteria if of childbearing potential. Males must adhere to criteria if w/ females of childbearing potential
- Patients must have previously untreated AML w/ no prior treatment other than hydroxyurea. No chemotherapy for AML outside of hydroxyurea for treatment of leukostasis or ATRA for initially suspected APL (that is ruled...
- If patient has co-morbid illness or malignancy, life expectancy attributed to this must be \>2 yrs S17 - EC
- Isolated myeloid sarcoma (must have blood or marrow involvement w/ AML)
- APL (FAB M3)
- Favorable risk cytogenetics (Core Binding Factor AML)
- Active CNS involvement by AML
- Signs of leukostasis requiring urgent therapy
- WBC ≥25,000/μl (WBC \<25,000/μl to begin therapy, Hydroxyurea may be used to obtain this level)
- Willing \& able to receive intensive chemotherapy
- DIC w/ active bleeding or signs of thrombosis
- Patients w/ psychological, familial, social, or geographic factors that otherwise preclude them from giving informed consent, following the protocol, or complying w/ study treatment \& follow-up
- Any significant medical condition, including psychiatric illness or lab abnormality, that would preclude the patient participating in the trial or would confound trial result interpretation
- Known active HIV, active hepatitis B or C infections
- Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure (CHF), unstable angina pectoris, serious cardiac arrhythmia, myocardial infarction (MI) as presentation of AML, New...
- Patients w/ uncontrolled infection shall not be enrolled until infection is treated \& brought under control
- Patients who have received an investigational agent (for any indication) w/in 5 half-lives of the agent \& until toxicity from this has resolved to ≤ grade 1; if half-life of the agent is unknown, patients must wait 4...
- Patients w/ QTcF \>450 ms (males), \>468 (females); patients w/ right, left, or partial bundle branch blocks (BBB) or pacemaker that may confound interpretation of this reading excluded provided they lack history of...
- ≥60 yrs at AML diagnosis
- ECOG score of 0, 1, or 2
- AST \<2.5 x ULN, ALT \<2.5 x ULN, \& total bilirubin \<1.5 x ULN (except for patients w/ known Gilbert's syndrome) for the local lab. If due to disease, higher values may be approved after discussion w/ medical monitor
- Adequate renal function as defined by calculated creatinine clearance \>40 mL/min per the local lab
- Patients must be able to understand \& provide written informed consent
- Females must be non-childbearing, postmenopausal, surgically sterile or meet certain criteria if of childbearing potential
- Males must adhere to criteria if w/ females of childbearing potential
- No prior chemotherapy for leukemia (hydroxyurea to control leukocytosis \& ATRA for initially suspected APL allowed). Prior therapy for MDS or myeloproliferative neoplasm (MPN) allowed (except for hypomethylating agents)
- If patient has co-morbid illness or malignancy, life expectancy attributed to this must be \>2 yrs S24 - EC
- Patients able \& willing to receive intensive chemotherapy for underlying AML
- Isolated myeloid sarcoma (must have blood or marrow involvement w/ AML)
- Known active CNS involvement by AML
- Clinical signs/symptoms of leukostasis requiring urgent therapy
- Known active HIV, active hepatitis B or C infections
- DIC w/ active bleeding or signs of thrombosis
- Patients who have received an investigational agent (for any indication) w/in 5 half-lives of the agent; if half-life of the agent is unknown, patients must wait 1 wk prior to first dose of study treatment
- Systemic antineoplastic therapy (for any indication) w/in 5 half-lives or radiation therapy w/in 1 wk prior to starting protocol except for hydroxyurea, which is allowed to control WBC counts
- Patients w/ psychological, familial, social, or geographic factors, any other significant medical condition, or a lab abnormality that otherwise precludes them from giving informed consent, following the protocol, or...
- Uncontrolled intercurrent illness including, but not limited to, symptomatic CHF, unstable angina pectoris, serious cardiac arrhythmia, MI w/in 6 months prior to enrollment (Troponin leak alone not included if no...
- Patients w/ uncontrolled infection shall not be enrolled until infection is treated \& brought under control
- Patients who require treatment w/ concomitant drugs that are strong inducers of cytochrome P450 (CYP) 3A
- Patients who require treatment w/ concomitant drugs that are strong inhibitors or inducers of P-glycoprotein (P-gp) w/ the exception of drugs that are considered absolutely essential for care of the patient S25/HO181 IC
- ≥18 yrs (or legal age of majority in jurisdiction where study is taking place, whichever is greater) at time of informed consent
- New diagnosis of AML (≥10% blasts in BM or peripheral blood) w/ mutated NPM1 or w/ recurring rearrangements involving KMT2A according to ICC 2022 criteria
- Considered eligible for intensive chemotherapy
- WHO/ECOG score ≤2
- Adequate renal \& hepatic functions prior to randomization S25/HO181 EC
- Prior (chemo-)therapy for AML, including prior treatment w/ hypomethylating agents
- Known active leukemic involvement of CNS
- Recipient of solid organ transplant
- Cardiac disease:
- Any of the following w/in 6 months of randomization: MI, uncontrolled/unstable angina, CHF (NYHA Class III or IV), uncontrolled or symptomatic arrhythmias, stroke, or transient ischemic attack
- QTcF ≥470 ms. Prolonged QTc interval associated w/ BBB or pacemaking is permitted
- Left ventricular ejection fraction (LVEF) \<40% by ECHO or MUGA scan obtained w/in 28 days prior to start of study treatment
- Previously received cumulative dose of any combination of anthracyclines or anthracenediones of ≥500 mg/m2
- Chronic respiratory disease requiring supplemental oxygen S26/HO177 - IC
- Patient w/ newly diagnosed NPM1-mutated AML, consistent w/ NPM1c, according to 2022 ICC (ie, ≥10% blasts). OR Patient w/ newly diagnosed KMT2A-rearranged AML according to 2022 ICC (ie, ≥10% blasts). KMT2A partial tandem...
- Central confirmation of NPM1 mutation or KMT2A rearrangement in 1 of the dedicated central genetic labs
- Age ≥18 yrs, no upper age limit
- Patient is ineligible for intensive chemotherapy by meeting at least 1 of the following criteria: A. ≥75 yrs: ineligible for intensive chemotherapy per physician's discretion (w/ an ECOG score 0-2) B. 18-74 yrs: patient...
- Patient must have a projected life expectancy of at least 12 wks (as assessed by treating physician)
- Patient must have a WBC count of \<25 x 109/L. Hydroxyurea can be used prior to study enrollment to reduce WBC count to meet this criterion
- Adequate renal function as evidenced by serum creatinine ≤2.0 × ULN or creatinine clearance \>30 mL/min based on Cockcroft-Gault glomerular filtration rate (GFR)
- Adequate hepatic function as evidenced by: A. Serum total bilirubin ≤ 3.0 × ULN unless considered due to Gilbert's disease, or leukemic involvement following written approval by sponsor (Co-)Principal Investigator B...
- Female patient must: A. be of nonchildbearing potential: o postmenopausal (defined as at least 1 yr w/out any menses). o documented surgically sterile (eg, documented hysterectomy, bilateral oophorectomy, bilateral...
- Consistent \& correct usage of established hormonal contraceptives that inhibit ovulation for at least 1 month prior to taking study drug. Hormonal contraception qualifies as a highly effective birth control method only...
- Established intrauterine device (IUD) or intrauterine system (IUS)
- Bilateral tubal occlusion
- Vasectomy - a highly effective contraception method provided the absence of sperm has been confirmed. If not, an additional highly effective method of contraception should be used
- Male is sterile due to a bilateral orchiectomy -- Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual activity during the entire period of risk associated w/ the...
- Men must use a latex condom during any sexual contact w/ women of childbearing potential, even if they have undergone a successful vasectomy \& must agree to avoid fathering a child (while on therapy \& for 6 months...
- Male patient must not donate sperm starting at screening \& throughout the study period \& for 6 months after the final study drug administration
- Able to understand \& willing to sign an informed consent form (ICF)
- Institutional Review Board/Independent Ethics Committee-approved written informed consent as per national regulations must be obtained from the patient prior to any study-related procedures (including consent for...
- Previously treated for AML; a treatment period w/ hydroxyurea to control WBC counts allowed; prior treatment w/ a hypomethylating agent for MDS-EB is not allowed; prior treatment w/ erythropoiesis-stimulating agents or...
- APL w/ t(15;17)(q24.1;q21.2); PML-RARA; or other pathognomonic variant chromosomal translocation/fusion gene
- AML w/ BCR-ABL1; or myeloid blast crisis of CML
- Significant active cardiac disease w/in 3 months prior to start of study treatment, including:
- NYHA class III or IV CHF
- Unstable angina
- Severe cardiac arrhythmias
- Congenital long QT syndrome of family member w/ this condition
- QTcF \>450 msec for males \& \>470 msec for females on screening electrogram (mean of triplicate recordings; calculated using Fridericia's correction)
- Severe obstructive or restrictive ventilation disorder
- History of stroke or intracranial hemorrhage w/in 6 months prior to randomization
- Clinical symptoms suggestive of active CNS leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid during screening is only required if there is a clinical suspicion of CNS involvement by leukemia during...
- Active infection, including hepatitis B or C or HIV infection, that is uncontrolled prior to first dose of study treatment \& may interfere w/ study objectives or could expose patient to undue risk through participation...
- Immediate life-threatening, severe complications of leukemia such as uncontrolled bleeding and/or DIC
- Conditions that limit ingestion or gastrointestinal absorption of orally administered drugs
- Patient w/ currently active second malignancy. Patients are not considered to have a currently active malignancy if they have completed therapy \& are considered by their physician to be at \< 30% risk of relapse w/in 1...
- Basal or squamous cell carcinoma of the skin
- Carcinoma in situ of the cervix
- Carcinoma in situ of the breast
- Incidental histologic finding of prostate cancer
- Receipt of live, attenuated vaccine w/in 30 days prior to study inclusion (NOTE: patient, if enrolled, should not receive live vaccine during the study \& until 6 months after therapy)
- Severe neurological or psychiatric disorder interfering w/ ability to give informed consent
- Contraindication to AZA or VEN (as per Summary of Product Characteristics)
- Weighing \<40 kg at registration
- Participation in other prospective studies w/ anti-leukemic and/or investigational agents
- Taking Dabigatran, unless patient can be transferred to other medications w/in ≥5 half-lives prior to dosing. Patients taking other P-gP transporter-sensitive medications should be properly monitored during the study if...
- Taking known strong cytochrome P450 (CYP) 3A4 inducers, unless patient can be transferred to other medications w/in ≥5 half-lives prior to dosing
- Pregnant or lactating woman or plans to become pregnant during the study
- Patient screened \& assigned by chance into this S26/HO177 trial but considered ineligible cannot re-enter this trial at later date
The study team makes the final eligibility decision.
Where it's taking place
- Phoenix, Arizona, United States
- Scottsdale, Arizona, United States
- Los Angeles, California, United States
- San Francisco, California, United States
- Denver, Colorado, United States
- Gainesville, Florida, United States
- Jacksonville, Florida, United States
- Orlando, Florida, United States
- Atlanta, Georgia, United States
- Augusta, Georgia, United States
- Chicago, Illinois, United States
- Fairway, Kansas, United States
- Pikeville, Kentucky, United States
- Baltimore, Maryland, United States
- Boston, Massachusetts, United States
- Rochester, Minnesota, United States
- St Louis, Missouri, United States
- New York, New York, United States
- Rochester, New York, United States
- Chapel Hill, North Carolina, United States
+ 9 more site(s).
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Phoenix, Arizona, United States; Scottsdale, Arizona, United States; Los Angeles, California, United States; San Francisco, California, United States; Denver, Colorado, United States; Gainesville, Florida, United States and 23 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.