Acute Myeloid LeukemiaPhase 1/2BSTPHASE1-01NCT02544438
Study Evaluating the Safety and Efficacy of Astarabine in Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia
A Phase 1/2 study testing Astarabine (BST-236) in people with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia, run by BioSight Ltd. at 2 sites in Israel.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia
- What is being tested?
- Astarabine (BST-236)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesIsrael
- Study dates
- Sep 2015to 20 Sep 2017
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- Refractory disease will be considered failure to either respond to induction chemotherapy and/or salvage therapy.
- 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.
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- 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).
Who cannot join
- 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.
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- 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.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to Astarabine/Ara-C.
- Pregnant women are excluded from this study because Astarabine/Ara-C are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Astarabine, breastfeeding should be discontinued if the mother is treated with Astarabine.
- known history of Human immunodeficiency virus (HIV) or active hepatitis B or C
- Concurrent use of the following medications: Digoxin, Gentamycin, fluorocytosine, L-asparginase, any drugs or supplements that interfere with blood clotting can raise the risk of bleeding during treatment with Ara-C. These include: vitamin E, non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, warfarin, ticlopidine, clopidogrel.
Trial locations and contacts
2 sites in 1 country.
Israel2 sites
Rambam medical center hematology department
Haifa, 4655202
Tel Aviv Sourasky Medical Center
Tel Aviv
About this study
Official title: 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
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
Read the detailed description
This is prospective, Phase I/IIa, open-label, uncontrolled, single-center, single arm study to evaluate the safety and efficacy of Astarabine given intravenously (I.V.) in escalated doses for 6 days for cycle in patients with relapsed or refractory AML or ALL who are more than 18 years of age. Patients will be screened for eligibility based on existing records and/or specific laboratory examinations performed for the screening process.
Patients will be gradually enrolled into 4 subsequent cohorts of escalating drug doses:
Cohort # Astarabine Dose Number of Patients
- 0.5 gr/m2 (0.3 age>50) 3
- 1.5 gr/m2 (0.8age>50) 3
- 3.0 gr/m2 (1.5 age>50) 3
- 4.5 gr/m2 (2.3 age>50) 6
- 4.5 gr/m2 (no age limit) 3 up to 6
- 6 gr/m2 (no age limit) 3 up to 6
Maximal tolerated dose (MTD) will be defined in case 2 subjects will experience a dose limiting toxicity (DLT)
- Being tested
- Astarabine (BST-236)
- Medical subject headings
- Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Astarabine (BST-236)Drug
Cohort # Astarabine Dose Number of Patients
- 0.5 gr/m2 (0.3 age>50) 3
- 1.5 gr/m2(0.8age>50) 3
- 3.0 gr/m2(1.5 age>50) 3
- 4.5 gr/m2(2.3 age>50) 6
- 4.5 gr/m2 (no age limit) 3 up to 6
- 6 gr/m2 (no age limit) 3 up to 6
Total number of patients: up to 24
| Study group | Role | What they receive |
|---|---|---|
| Astarabine | Experimental | Astarabine Receives: Drug: Astarabine (BST-236) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal tolerated dose (MTD)
Measured: 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.
Measured: within 90 days
Secondary outcomes (4)
safety and tolerability expressed by any grade adverse events (AEs)
Measured: within 90 days
PharmacoKintetics (PK): maximum plasma concentration (Cmax)
Measured: 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)
using the revised recommendations of the international working group for diagnosis, standardization of response criteria, tratment outcome and reporting stanndadarts fro therapeutic trials in acute myeloid leukemia
Measured: within 90 days
Phrmacokinetics (PK): area under the curve (AUC) versus time curve
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2015 (estimated)
- Study startSep 2015
- Primary completion20 Sep 2017
- Study completion20 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- BioSight Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Tsila Zuckerman, MD, Principal investigator, Rambam Health Care Campus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02544438
- Sponsor's protocol ID
- BST-PHASE1-01
- Acronym
- BSTPHASE1-01
- Status last verified
- Sep 2017
- First submitted
- 23 Aug 2015
- Last updated
- 27 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 31770437
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02544438
- Acronym / sponsor ID
- BSTPHASE1-01 / BST-PHASE1-01
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- BioSight Ltd.Industry (pharma, biotech, devices)
- Study start
- Sep 2015
- Primary completion
- 20 Sep 2017 (actual)
- Study completion
- 20 Sep 2017 (actual)
- First posted
- 9 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
This is prospective, Phase I/IIa, open-label, uncontrolled, single-center, single arm study to evaluate the safety and efficacy of Astarabine given intravenously (I.V.) in escalated doses for 6 days for cycle in patients with relapsed or refractory AML or ALL who are more than 18 years of age. Patients will be screened for eligibility based on existing records and/or specific laboratory examinations performed for the screening process.
Patients will be gradually enrolled into 4 subsequent cohorts of escalating drug doses:
Cohort # Astarabine Dose Number of Patients
- 0.5 gr/m2 (0.3 age>50) 3
- 1.5 gr/m2 (0.8age>50) 3
- 3.0 gr/m2 (1.5 age>50) 3
- 4.5 gr/m2 (2.3 age>50) 6
- 4.5 gr/m2 (no age limit) 3 up to 6
- 6 gr/m2 (no age limit) 3 up to 6
Maximal tolerated dose (MTD) will be defined in case 2 subjects will experience a dose limiting toxicity (DLT)
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Astarabine | Experimental | Drug: Astarabine (BST-236)Astarabine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
- 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.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Astarabine (BST-236)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 | Drug | Astarabine |
Primary outcome
Maximal tolerated dose (MTD)
Time frame: 90 days
Dose limiting Toxicity (DLTs)
Time frame: within 90 days
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.
4 secondary outcomes
safety and tolerability expressed by any grade adverse events (AEs)
Time frame: within 90 days
PharmacoKintetics (PK): maximum plasma concentration (Cmax)
Time frame: 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)
Time frame: within 90 days
Phrmacokinetics (PK): area under the curve (AUC) versus time curve
Time frame: 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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2017.
- Derived from this study: PubMed 31770437Zuckerman 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tsila Zuckerman, MD principal investigator
Rambam Health Care Campus
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Astarabine (BST-236) in people with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia, run by BioSight Ltd. at 2 sites in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximal tolerated dose (MTD) (time frame: 90 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02544438, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2017.