AZD1775 in Advanced Acute Myeloid Leukemia, Myelodysplastic Syndrome and Myelofibrosis

NCT03718143 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 17-01816
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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 being allocated to either the combination Arm B or single agent AZD1775 Arm C.

Conditions

Myelofibroses; Acute Myeloid Leukemia; Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (1)

• 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.

  4 months

Secondary Outcomes (2)

• Incomplete Measure of Complete Remission (CRi)

  4 months

• Complete Cytogenetic Remission (CCyR)

  4 Months

Study Arms (3)

Arm A: Elderly Newly diagnosed AML

EXPERIMENTAL

Combination AZD1775 with AraC Elderly, newly diagnosed AML

Drug: Combination AZD1775 with AraC

Arm B:Relapsed AML and MDS

EXPERIMENTAL

Combination AZD1775 with AraC Relapsed/Refractory AML \& HMA failure AML/ MDS

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

Drug: AZD1775 only

Interventions

Combination AZD1775 with AraC DRUG

AZD1775 days 1-5 \& 8-12 AraC days 1-5 \& 8-12

Arm A: Elderly Newly diagnosed AML; Arm B:Relapsed AML and MDS

AZD1775 only DRUG

AZD1775 days 1-5 \& 8-12

Arm C: Relapsed AML, MDS and MF

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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).

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

NYU Langone Health

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Primary Myelofibrosis; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms

Results Point of Contact

• Title: Rachael Keller, Sr. Regulatory Specialist
• Organization: NYU Langone Health - PCC CTO

Rachael.Keller@nyulangone.org

929-455-2453

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2018
• First Posted: October 24, 2018
• Study Start: May 8, 2019
• Primary Completion: September 27, 2019
• Study Completion: September 27, 2019
• Last Updated: June 2, 2020
• Results First Posted: June 2, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• Access Criteria: The investigator who proposed to use the data.

Locations

US (1)