Brief Summary
Phase 1/1b, open label, multi-center dose escalation and dose expansion study designed to evaluate safety, tolerability, PK (pharmacokinetics), PD (pharmacodynamics) and anti-tumor effects of ALRN-6924 alone or in combination with cytarabine in patients with relapsed/refractory acute myeloid leukemia or advanced myelodysplastic syndrome with wild-type (WT) TP53
Brief Title
Safety Study of ALRN-6924 in Patients With Acute Myeloid Leukemia or Advanced Myelodysplastic Syndrome
Detailed Description
Phase I, open label, multi-center dose escalation (DEP) and dose expansion (EXP) study designed to evaluate safety, tolerability, PK (pharmacokinetics), PD (pharmacodynamics) and anti-tumor effects of ALRN-6924 in patients with acute myeloid leukemia or advanced myelodysplastic syndrome with wild-type (WT) TP53. ALRN-6924 is a stabilized cell-permeating peptide designed to disrupt interaction between the p53 tumor suppression protein and its endogenous inhibitors murine double minute 2 (MDM2) and murine double minute X (MDMX)
Men and women 18 years of age and older with relapsed or refractory acute myeloid leukemia or advanced myelodysplastic syndrome and for which standard treatment(s) are not available or are no longer effective can be enrolled. Treatment of patients in the DEP and EXP phases will continue in the study until documentation of disease progression, unacceptable toxicity, or patient or physician decision to discontinue study participation is made.
Men and women 18 years of age and older with relapsed or refractory acute myeloid leukemia or advanced myelodysplastic syndrome and for which standard treatment(s) are not available or are no longer effective can be enrolled. Treatment of patients in the DEP and EXP phases will continue in the study until documentation of disease progression, unacceptable toxicity, or patient or physician decision to discontinue study participation is made.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Acute Myeloid Leukemia
Myelodysplastic Syndromes
Eligibility Criteria
Inclusion Criteria:
* Relapsed or refractory acute myeloid leukemia or IPSS-R intermediate/high/very high-risk MDS patients
* Confirmed or anticipated wild-type TP53
* ECOG (Eastern Cooperative Oncology Group) performance status 0-2
* Adequate hepatic and renal function
* Acceptable coagulation function
* Negative serum or urine pregnancy test within 7 days prior to the first dose of ALRN-6924 for women of child-bearing potential
* Sufficient wash out from prior therapies and recovery from all significant toxicities
Exclusion Criteria:
* Patients are eligible for available approved standard therapies
* Prior treatment with MDM2 inhibitor, with protocol specified exceptions
* Patients with history of allogeneic stem cell transplantation
* Leukemic blast counts of \>25,000/µl
* Deletion of chromosome 17, or del(17p)
* Patients with evidence of current central nervous system leukemic involvement
* Known hypersensitivity to any study drug component
* History of coagulopathy
* Prior specified cardiovascular risk factors
* Clinically significant gastrointestinal bleeding within 6 months
* Clinically significant third-space fluid accumulation
* Pregnant or lactating females
* Evidence of any serious and/or unstable pre-existing medical condition that would interfere with patient safety ability to provide informed consent
* Active uncontrolled infection, including HIV/AIDS or Hepatitis B or C
* Second malignancy within one year, with protocol specified exceptions
* Relapsed or refractory acute myeloid leukemia or IPSS-R intermediate/high/very high-risk MDS patients
* Confirmed or anticipated wild-type TP53
* ECOG (Eastern Cooperative Oncology Group) performance status 0-2
* Adequate hepatic and renal function
* Acceptable coagulation function
* Negative serum or urine pregnancy test within 7 days prior to the first dose of ALRN-6924 for women of child-bearing potential
* Sufficient wash out from prior therapies and recovery from all significant toxicities
Exclusion Criteria:
* Patients are eligible for available approved standard therapies
* Prior treatment with MDM2 inhibitor, with protocol specified exceptions
* Patients with history of allogeneic stem cell transplantation
* Leukemic blast counts of \>25,000/µl
* Deletion of chromosome 17, or del(17p)
* Patients with evidence of current central nervous system leukemic involvement
* Known hypersensitivity to any study drug component
* History of coagulopathy
* Prior specified cardiovascular risk factors
* Clinically significant gastrointestinal bleeding within 6 months
* Clinically significant third-space fluid accumulation
* Pregnant or lactating females
* Evidence of any serious and/or unstable pre-existing medical condition that would interfere with patient safety ability to provide informed consent
* Active uncontrolled infection, including HIV/AIDS or Hepatitis B or C
* Second malignancy within one year, with protocol specified exceptions
Inclusion Criteria
Inclusion Criteria:
* Relapsed or refractory acute myeloid leukemia or IPSS-R intermediate/high/very high-risk MDS patients
* Confirmed or anticipated wild-type TP53
* ECOG (Eastern Cooperative Oncology Group) performance status 0-2
* Adequate hepatic and renal function
* Acceptable coagulation function
* Negative serum or urine pregnancy test within 7 days prior to the first dose of ALRN-6924 for women of child-bearing potential
* Sufficient wash out from prior therapies and recovery from all significant toxicities
* Relapsed or refractory acute myeloid leukemia or IPSS-R intermediate/high/very high-risk MDS patients
* Confirmed or anticipated wild-type TP53
* ECOG (Eastern Cooperative Oncology Group) performance status 0-2
* Adequate hepatic and renal function
* Acceptable coagulation function
* Negative serum or urine pregnancy test within 7 days prior to the first dose of ALRN-6924 for women of child-bearing potential
* Sufficient wash out from prior therapies and recovery from all significant toxicities
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02909972
Org Class
Industry
Org Full Name
Aileron Therapeutics, Inc.
Org Study Id
ALRN-6924-1-02
Overall Status
Completed
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 1/1b Open-Label Study to Determine the Safety and Tolerability of ALRN-6924 Alone and in Combination With Cytarabine (Ara-C) in Patients With Relapsed/Refractory Acute Myeloid Leukemia or Advanced Myelodysplastic Syndrome With Wild-Type TP53
Primary Outcomes
Outcome Description
Number of participants with treatment-related adverse events as assessed by CTCAE v.4.0
Outcome Measure
Evaluate the safety and tolerability of ALRN-6924 alone and in combination with cytarabine
Outcome Time Frame
From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle is 28 days)
Outcome Description
Determine the dose limiting toxicities (DLT) and the maximum tolerated dose (MTD) or the optimal biological dose (OBD) of ALRN-6924 in adult patients with AML or MDS
Outcome Measure
Determine maximum tolerated dose (MTD)
Outcome Time Frame
From the first dose until the end of Cycle 2 (each cycle is 28 days)
Secondary Outcomes
Outcome Description
Peak Plasma Concentration (Cmax)
Outcome Time Frame
First 2 cycles (each cycle is 28 days)
Outcome Measure
Determine PK parameters of ALRN-6924 when administered to patients with acute myeloid leukemia (AML) or advanced myelodysplastic syndrome (MDS)
Outcome Description
Area under the plasma concentration versus time curve \[AUC\]
Outcome Time Frame
First 2 cycles (each cycle is 28 days)
Outcome Measure
Determine PK parameters of ALRN-6924 when administered to patients with acute myeloid leukemia (AML) or advanced myelodysplastic syndrome (MDS)
Outcome Description
Incidence of anti-ALRN-6924 antibodies
Outcome Time Frame
Approximately 16 weeks
Outcome Measure
Determine immunogenicity of ALRN-6924
Outcome Description
International Working Group (IWG) Criteria (Cheson et al, 2006)
Outcome Time Frame
Approximately 16 weeks
Outcome Measure
Determine best overall response, duration of response, morphologic leukemia-free state, leukemia free survival, percentage of MDA patients who have achieved hematologic improvement, changes in transfusion rate and early death rate
Outcome Description
AML response criteria (Dohner et al, 2010)
Outcome Time Frame
Approximately 16 weeks
Outcome Measure
Determine best overall response, duration of response, morphologic leukemia-free state, leukemia free survival, percentage of MDA patients who have achieved hematologic improvement, changes in transfusion rate and early death rate
Outcome Description
International Working Group (IWG) Criteria for hematological improvement in MDS (Cheson et al, 2000)
Outcome Time Frame
Approximately 16 weeks
Outcome Measure
Determine best overall response, duration of response, morphologic leukemia-free state, leukemia free survival, percentage of MDA patients who have achieved hematologic improvement, changes in transfusion rate and early death rate
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Amit Verma
Investigator Email
amit.verma@einsteinmed.org
Investigator Phone
718-405-8505 / 718-904-2900
Categories Mesh Debug
Blood & Bone Marrow Cancers --- LEUKEMIA, MYELOID, ACUTE
Blood & Bone Marrow Cancers --- MYELODYSPLASTIC SYNDROMES
Blood & Bone Marrow Cancers --- LEUKEMIA, MYELOID
Cancer --- LEUKEMIA
Blood & Bone Marrow Cancers --- LEUKEMIA
Cancer --- NEOPLASMS
Blood Disorders --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- BONE MARROW DISEASES
MeSH Terms
LEUKEMIA, MYELOID, ACUTE
MYELODYSPLASTIC SYNDROMES
LEUKEMIA, MYELOID
LEUKEMIA
NEOPLASMS BY HISTOLOGIC TYPE
NEOPLASMS
HEMATOLOGIC DISEASES
HEMIC AND LYMPHATIC DISEASES
BONE MARROW DISEASES
CYTARABINE
CYTIDINE
PYRIMIDINE NUCLEOSIDES
PYRIMIDINES
HETEROCYCLIC COMPOUNDS, 1-RING
HETEROCYCLIC COMPOUNDS
ARABINONUCLEOSIDES
NUCLEOSIDES
NUCLEIC ACIDS, NUCLEOTIDES, AND NUCLEOSIDES