Study Evaluating the Safety and Efficacy of Astarabine in Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia

NCT02544438 | Completed Phase 1 DMC

• 1 other identifier: BST-PHASE1-01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

A Phase I/IIa, open-label, uncontrolled study to evaluate the safety and efficacy of Astarabine (BST-236) as single agent in patients with refractory or relapsed Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL) disease

Conditions

Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (2)

• Maximal tolerated dose (MTD)

  90 days

• Dose limiting Toxicity (DLTs)

  Any ≥ grade 3 non-hematologic toxicity (excluding alopecia, hypersensitivity) Grade 3 nausea and vomiting if it occurs despite maximal (5HT antagonist and corticosteroid) antiemetic therapy, and if hydration is required for \>24 hours. Grade 3 diarrhea despite patient compliance with loperamide therapy.

  within 90 days

Secondary Outcomes (4)

• safety and tolerability expressed by any grade adverse events (AEs)

  within 90 days

• PharmacoKintetics (PK): maximum plasma concentration (Cmax)

  PK studies will be performed up to 8 days at the following time points: 0', 15', 30', 60', 90', 120', 240', 360', and 600' of days: 1 to 6 and 24 hours and 48 hours after last Astarabine administration (days 7 - 8)

• response rate: complete remission + partial remission (CR + PR)

  within 90 days

• Phrmacokinetics (PK): area under the curve (AUC) versus time curve

  PK studies will be performed up to 8 days at the following time points: 0', 15', 30', 60', 90', 120', 240', 360', and 600' of days: 1 to 6 and 24 hours and 48 hours after last Astarabine administration (days 7 - 8)

Study Arms (1)

Astarabine

EXPERIMENTAL

Astarabine

Drug: Astarabine (BST-236)

Interventions

Astarabine (BST-236) DRUG

Cohort # Astarabine Dose Number of Patients 1. 0.5 gr/m2 (0.3 age\>50) 3 2. 1.5 gr/m2(0.8age\>50) 3 3. 3.0 gr/m2(1.5 age\>50) 3 4. 4.5 gr/m2(2.3 age\>50) 6 5. 4.5 gr/m2 (no age limit) 3 up to 6 6. 6 gr/m2 (no age limit) 3 up to 6 Total number of patients: up to 24

Astarabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A. Relapsed or refractory acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), based on World Health Organization Classification; Patients must have morphological proof of AML or ALL with blasts in peripheral blood (PB) or 5% in bone marrow (BM) within 2 weeks prior to study registration.
• I. Refractory disease will be considered failure to either respond to induction chemotherapy and/or salvage therapy.
• II. 2nd relapse III. Relapse following autologous or allogeneic stem cell transplantation. B. patients which at the physician discretion are not eligible for standard chemotherapy, whether induction or consolidation, due to age or significant co-morbidities
• Age ≥18 years.
• Ability to understand and willingness to sign the written informed consent document.
• Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment and use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Male subject agrees to use an acceptable method for contraception for the duration of the study.
• Eastern cooperative oncology group (ECOG) performance status ≤ 2
• Hydroxyurea is permitted to control high white blood cells (WBC) count prior to study entry.
• Previous treatment related toxicities must have resolved to less than Grade 2 (excluding alopecia).

You may not qualify if:

• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. l. Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, uncontrolled hypertension, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant.
• Patients with compromised pulmonary function who needs oxygen therapy.
• Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.
• Patients who have had chemotherapy (except for hydroxyurea), biologic therapy, immunotherapy, or radiotherapy within 2 weeks of induction therapy or 4 weeks of consolidation or intensive therapy (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Patients receiving any other investigational agents.
• Patients who have had any surgical procedure, excluding central venous catheter placement or other minor procedures (e.g. skin biopsy) within 14 days of Day 1.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Patients with prior malignancy are eligible; however, the patient must be in remission from the prior malignancy and have completed all chemotherapy and radiotherapy at least 6 months prior to registration and all treatment-related toxicities must have resolved.
• Leptomeningeal/ central nervous system involvement with AML; a lumbar puncture does not need to be performed unless there is clinical suspicion.
• Patients with active central nervous system disease or with granulocytic sarcoma as sole site of disease.
• Patients who have had prior pulmonary radiation.
• Liver enzymes (AST and alanine aminotransferase (ALT) more than 2.5 times the upper limits of normal (ULN), and total bilirubin more than 1.5 x ULN within 14 days of enrollment.
• Renal function: Serum creatinine more than 1.5 x ULN within 24 hours of enrollment.
• Existence of inter-current organ damage or medical condition that would prohibit or interfere with study drug therapy.
• If the patient has co-morbid medical illness, life expectancy attributed to this must be greater than 3 months.

Sponsors & Collaborators

• BioSight Ltd.: lead

Study Sites (2)

Rambam medical center hematology department

Haifa, 4655202, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel

Location

Related Publications (1)

• Zuckerman T, Ram R, Akria L, Koren-Michowitz M, Hoffman R, Henig I, Lavi N, Ofran Y, Horowitz NA, Nudelman O, Tavor S, Yeganeh S, Gengrinovitch S, Flaishon L, Tessler S, Ben Yakar R, Rowe JM. BST-236, a novel cytarabine prodrug for patients with acute leukemia unfit for standard induction: a phase 1/2a study. Blood Adv. 2019 Nov 26;3(22):3740-3749. doi: 10.1182/bloodadvances.2019000468.

  PMID: 31770437 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Tsila Zuckerman, MD

  Rambam Health Care Campus

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2015
• First Posted: September 9, 2015
• Study Start: September 1, 2015
• Primary Completion: September 20, 2017
• Study Completion: September 20, 2017
• Last Updated: September 27, 2017

Record last verified: 2017-09

Locations

IL (2)