MyelofibrosesPhase 2NCT03718143
AZD1775 in Advanced Acute Myeloid Leukemia, Myelodysplastic Syndrome and Myelofibrosis
A Phase 2 study testing Combination AZD1775 with AraC and AZD1775 only in people with Myelofibroses and Acute Myeloid Leukemia, run by NYU Langone Health at 1 site in United States.
Trial summary
A phase II study testing the efficacy of combined AZD1775 with AraC or single agent activity of AZD1775 in three arms: Arm A has subjects age 60 years or older who are newly diagnosed with AML receiving the combination of the drugs; Arm B has subjects who are have relapsed/refractory AML and HMA failure MDS patients… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Myelofibroses, Acute Myeloid Leukemia, Myelodysplastic Syndromes
- What is being tested?
- Combination AZD1775 with AraC and AZD1775 only
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 8 May 2019to 27 Sep 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Dose escalation part of trial for combined AraC + AZD1775 (Arm A)
- untreated elderly (>60 years) AML if in the poor-risk cytogenetic group (please reference Appendix V).
- untreated elderly (>60 years) AML if in the intermediate and poor-risk cytogenetic group (please reference Appendix V)
- relapsed or refractory AML (≥ 18 years)
- any MDS (≥ 18 years) having failed or been intolerant to prior hypomethylating agent (HMA) treatment.
- Failure is defined as any disease progression while on HMA, relapse after HMA treatment or no response after 4 cycles of 5-Azacitidine or decitabine
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- Patients with isolated 5q-/5q- syndrome must have failed, not tolerated, or progressed on lenalidomide in addition to having failed or been intolerant to HMA treatment.
- advanced progressive MF, defined as intermediate and high risk primary and secondary MF, or any other MF failed or intolerant to JAK2 inhibitor therapy requiring medical therapy
- If appropriate, patients can have failed other prior therapies for their disease (i.e. JAK2 inhibitor, interferon, hydroxyurea or IMIDs). Patients may have failed more than one JAK2 inhibitor and JAK2 inhibitor must not have been the most recent treatment (e.g. other therapies as last therapy prior to study given after failure of previous JAK2 inhibitor).
- Failure/ intolerance of Ruxolitinib
- The following laboratory values obtained 7 days prior to registration.
- Total bilirubin ≤ 1.5 mg/dL (except Gilbert's syndrome or known hemolysis or leukemic infiltration)
- AST (SGOT) and ALT (SGPT) ≤ 2.5 x Upper Limit normal (ULN) or < 5 x ULN if organ involvement
- Alkaline Phosphatase < 5 x ULN - Serum creatinine ≤1.5 x ULN, or measured creatinine clearance (CrCl) ≥45 mL/min as calculated by the Cockcroft-Gault method (confirmation of creatinine clearance is only required when creatinine is >1.5 x institutional ULN) CrCl (glomerular filtration rate [GFR]) = (140-age) x (weight/kg) x Fa (72 x serum creatinine mg/dL) a where F= 0.85 for females and F=1 for males
- ECOG Performance Status (PS) 0, 1 (Appendix I).
- Ability to provide informed written consent and be able to adhere to the study visit schedule and other protocol requirements.
- Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).
- Willing to provide blood and bone marrow aspirate samples for correlative research purposes
- Negative serum pregnancy test done ≤7 days prior to registration, for women of childbearing potential only.
- Female patients who are not of child-bearing potential and fertile females of childbearing potential
- Male patients should be willing to abstain or use barrier contraception (i.e., condoms) for the duration of the study drug exposure and for 3 months after study treatment discontinuation.
- Patients who have undergone stem cell transplantation (SCT), autologous or allogeneic, are eligible provided that they are > 60 days from stem cell infusion, have GVHD < grade 1 and are off immunosuppressive agents for > 28 days at time of registration.
Who cannot join
- AML patients who are suitable for and willing to receive intensive chemotherapy
- Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception
- Subject has had prescription or non-prescription drugs or other products known to be sensitive CYP3A4 substrates or CYP3A4 substrates
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- The preferred azole anti-fungal medication is Fluconazole (alternatively Posaconazole) which can be given during treatment with AZD1775 (section 9.5).
- Pateints may not be on an inhibitor of BCRP as outlined in Appendix VI.
- Not willing to avoid grapefruit, grapefruit juices, grapefruit hybrids, Seville oranges, pummelos, and exotic citrus fruits from 7 days prior to the dose of study medication
- Mean resting corrected QTc interval using the Fridericia formula (QTcF) >450 msec/male and >470 msec/female (as calculated per institutional standards) obtained from 3 electrocardiograms (ECGs) 2-5 minutes apart at study entry, or congenital long QT syndrome
- Herbal preparations/medications
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 2 Study of WEE1 Inhibition and AZD1775 Alone or Combined With Cytarabine in Patients With Advanced Acute Myeloid Leukemia, Myelodysplastic Syndrome and Myelofibrosis
A phase II study testing the efficacy of combined AZD1775 with AraC or single agent activity of AZD1775 in three arms: Arm A has subjects age 60 years or older who are newly diagnosed with AML receiving the combination of the drugs; Arm B has subjects who are have relapsed/refractory AML and HMA failure MDS patients being allocated to either the combination Arm B or single agent AZD1775 Arm C.
Read the detailed description
A phase II study testing the clinical efficacy of combined AZD1775 with AraC or single agent activity of AZD1775 in three patient strata: Elderly(> 60 years) newly diagnosed AML patients (Arm A) will only receive the combination; whereas relapsed/refractory AML patients and HMA failure MDS patients will be allocated to either the combination (Arm B) or single agent AZD1775 (Arm C). The study will have a run in safety cohort of six patients in each of the three arms to determine the safe use of combined AraC /AZD1775 or single agent AZD1775 in the patient populations. This will be followed by an expansion phase of up to 20 and 21 eligible patients in each arm respectively where elderly patients with newly diagnosed AML will receive a combination of AZD1775 and AraC (Arm A) while patients with relapsed or refractory AML or HMA failure MDS will be allocated to receive either AZD1775 with AraC (Arm B) or AZD1775 alone (Arm C). An early toxicity check will be conducted to determine safety and tolerability. If indicated, dose levels will be reduced. The study will continue to enroll the rest of the patients at the tolerated dose.
- Being tested
- Combination AZD1775 with AraC, AZD1775 only
- Medical subject headings
- Primary Myelofibrosis, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combination AZD1775 with AraCDrug
AZD1775 days 1-5 \& 8-12 AraC days 1-5 \& 8-12
AZD1775 onlyDrug
AZD1775 days 1-5 \& 8-12
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Elderly Newly diagnosed AML | Experimental | Combination AZD1775 with AraC
Elderly, newly diagnosed AML Receives: Drug: Combination AZD1775 with AraC |
| Arm B:Relapsed AML and MDS | Experimental | Combination AZD1775 with AraC
Relapsed/Refractory AML \& HMA failure AML/ MDS Receives: Drug: Combination AZD1775 with AraC |
| Arm C: Relapsed AML, MDS and MF | Active comparator | AZD1775 only
Relapsed/Refractory AML \& HMA failure AML/ MDS and Relapsed/Refractory Primary \& Secondary MF Receives: Drug: AZD1775 only |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Remission (CR) Rate
Less than 5% blasts in a non-hypocellular marrow with a granulocyte count ≥ 1.0, and a platelets count of ≥ 100 with complete resolution of extramedullary disease and absence of peripheral blood blasts.
Measured: 4 months
Secondary outcomes (2)
Incomplete Measure of Complete Remission (CRi)
is called if patient meets all CR criteria except for residual neutropenia (ANC<1 x109/L) or thrombocytopenia (platelets<100 x109/L)
Measured: 4 months
Complete Cytogenetic Remission (CCyR)
The absence of chromosome abnormalities (if present at diagnosis) on conventional cytogenetic study using G-banding (at least 10 metaphases present).
Measured: 4 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2018
- Study start8 May 2019
- Primary completion27 Sep 2019
- Study completion27 Sep 2019
Why it stopped: Safety concerns
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MyelofibrosesStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03718143
- Sponsor's protocol ID
- 17-01816
- Status last verified
- May 2020
- First submitted
- 8 Oct 2018
- Last updated
- 2 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices). Upon reasonable request.
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of WEE1 Inhibition and AZD1775 Alone or Combined With Cytarabine in Patients With Advanced Acute Myeloid Leukemia, Myelodysplastic Syndrome and Myelofibrosis
- ClinicalTrials.gov ID
- NCT03718143
- Acronym / sponsor ID
- 17-01816
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Safety concerns
- Enrolment
- 6 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Study start
- 8 May 2019 (actual)
- Primary completion
- 27 Sep 2019 (actual)
- Study completion
- 27 Sep 2019 (actual)
- First posted
- 24 Oct 2018 (actual)
- Results
- Posted 2 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A phase II study testing the efficacy of combined AZD1775 with AraC or single agent activity of AZD1775 in three arms: Arm A has subjects age 60 years or older who are newly diagnosed with AML receiving the combination of the drugs; Arm B has subjects who are have relapsed/refractory AML and HMA failure MDS patients being allocated to either the combination Arm B or single agent AZD1775 Arm C.
Detailed description
A phase II study testing the clinical efficacy of combined AZD1775 with AraC or single agent activity of AZD1775 in three patient strata: Elderly(> 60 years) newly diagnosed AML patients (Arm A) will only receive the combination; whereas relapsed/refractory AML patients and HMA failure MDS patients will be allocated to either the combination (Arm B) or single agent AZD1775 (Arm C). The study will have a run in safety cohort of six patients in each of the three arms to determine the safe use of combined AraC /AZD1775 or single agent AZD1775 in the patient populations. This will be followed by an expansion phase of up to 20 and 21 eligible patients in each arm respectively where elderly patients with newly diagnosed AML will receive a combination of AZD1775 and AraC (Arm A) while patients with relapsed or refractory AML or HMA failure MDS will be allocated to receive either AZD1775 with AraC (Arm B) or AZD1775 alone (Arm C). An early toxicity check will be conducted to determine safety and tolerability. If indicated, dose levels will be reduced. The study will continue to enroll the rest of the patients at the tolerated dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A: Elderly Newly diagnosed AML | Experimental | Drug: Combination AZD1775 with AraCCombination AZD1775 with AraC Elderly, newly diagnosed AML |
| Arm B:Relapsed AML and MDS | Experimental | Drug: Combination AZD1775 with AraCCombination AZD1775 with AraC Relapsed/Refractory AML \& HMA failure AML/ MDS |
| Arm C: Relapsed AML, MDS and MF | Active comparator | Drug: AZD1775 onlyAZD1775 only Relapsed/Refractory AML \& HMA failure AML/ MDS and Relapsed/Refractory Primary \& Secondary MF |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Dose escalation part of trial for combined AraC + AZD1775 (Arm A)
- untreated elderly (>60 years) AML if in the poor-risk cytogenetic group (please reference Appendix V).
- untreated elderly (>60 years) AML if in the intermediate and poor-risk cytogenetic group (please reference Appendix V)
- relapsed or refractory AML (≥ 18 years)
- any MDS (≥ 18 years) having failed or been intolerant to prior hypomethylating agent (HMA) treatment.
Key exclusion criteria (11 listed)
- AML patients who are suitable for and willing to receive intensive chemotherapy
- Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
- Subject has had prescription or non-prescription drugs or other products known to be sensitive CYP3A4 substrates or CYP3A4 substrates
- The preferred azole anti-fungal medication is Fluconazole (alternatively Posaconazole) which can be given during treatment with AZD1775 (section 9.5).
- Pateints may not be on an inhibitor of BCRP as outlined in Appendix VI.
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 |
|---|---|---|
| Combination AZD1775 with AraCAZD1775 days 1-5 \& 8-12 AraC days 1-5 \& 8-12 | Drug | Arm A: Elderly Newly diagnosed AML, Arm B:Relapsed AML and MDS |
| AZD1775 onlyAZD1775 days 1-5 \& 8-12 | Drug | Arm C: Relapsed AML, MDS and MF |
Primary outcome
Complete Remission (CR) Rate
Time frame: 4 months
Less than 5% blasts in a non-hypocellular marrow with a granulocyte count ≥ 1.0, and a platelets count of ≥ 100 with complete resolution of extramedullary disease and absence of peripheral blood blasts.
2 secondary outcomes
Incomplete Measure of Complete Remission (CRi)
Time frame: 4 months
Complete Cytogenetic Remission (CCyR)
Time frame: 4 Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices). Upon reasonable request.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Combination AZD1775 with AraC and AZD1775 only in people with Myelofibroses and Acute Myeloid Leukemia, run by NYU Langone Health at 1 site in United States.
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 22 inclusion and 11 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: stopped early, as of the sponsor's last update on 2 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 phase mean?
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?
Yes. Results are posted in the registry (first posted 2 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Complete Remission (CR) Rate (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Jun 2020.