Pevonedistat and Azacitidine as Maintenance Therapy After Allogeneic Stem Cell Transplantation for Non-Remission AML

NCT03709576 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: PSCI 17-056
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This research is being done to find out the toxicity and efficacy of a combination of Pevonedistat and Azacitidine as post allogeneic hematopoietic stem cell transplant maintenance therapy for non-remission AML and to see the overall diseases free survival, relapse, and GVHD after treatment.

Conditions

Acute Myeloid Leukemia (AML)

Outcome Measures

Primary Outcomes (3)

• One Year Overall Survival Assessed by the Kaplan-Meier Plots

  One year overall survival assess by Kaplan Meier Plots

  1 year

• To Assess the Toxicity and Efficacy of a Combination of Pevonedistat and Azacitidine as Post Allogeneic Hematopoietic Stem Cell Transplant Maintenance Therapy for Non-remission AML.

  Toxicity and efficacy unable to be determined as trial was closed by the sponsor prior to meeting this objective.

  not analyzed

• Toxicity Related to Pevonedistat

  Toxicity related to Pevonedistat unable to be determined as trial was closed by sponsor prior to meeting this objective

  not analyzed

Secondary Outcomes (6)

• To Assess the Overall Disease Free Survival, Relapse, and GVHD After the Above Noted Treatment

  not analyzed

• One-year Disease-free Survival

  not analyzed

• Cumulative Incidence of Relapse at 2 Years

  not analyzed

• Two-year and Five-year Disease-free and Overall Survival

  not analyzed

• Treatment Related Mortality/Morbidity

  not analyzed

Study Arms (1)

Pevonedistat and Azacitidine

EXPERIMENTAL

The study period is from the start of study treatment, cycle 1 day 1 until 28 days after the last treatment dose. (Cycle 5 day 9). Treatment will be continued until cycle 5 is completed or the study is terminated for the patient. The cycles will be repeated every 28 days. Cycle 1 Day 1 of study treatment will be between day +30 and day +45 post-transplant. Each 28-day cycle is comprised of Pevonedistat at 20 mg/m2 IV infusion over 1 hour on days 1, 3 and 5 and Azacitidine at 25 mg/m2 IV infusion over 30 minutes on days 1, 2, 3, 4, 5, 8 and 9. The drugs can be administered either through a central catheter or a peripheral line.

Drug: Pevonedistat; Procedure: transplant; Drug: Azacitidine

Interventions

Pevonedistat DRUG

To assess the toxicity and efficacy of a combination of Pevonedistat and Azacitidine as post allogeneic hematopoietic stem cell transplant maintenance therapy for non-remission AML.

Pevonedistat and Azacitidine

transplant PROCEDURE

Although hematopoietic stem cell transplantation (HSCT) is curative for many patients with AML, AML in relapse at the time of transplant is still a major challenge with low rates of leukemia-free survival even with an intensive myeloablative conditioning.

Pevonedistat and Azacitidine

Azacitidine DRUG

To assess the toxicity and efficacy of a combination of Pevonedistat and Azacitidine as post allogeneic hematopoietic stem cell transplant maintenance therapy for non-remission AML.

Pevonedistat and Azacitidine

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years (or age of majority at participating site, whichever is greater) and ≤ 70 years.
• Non-remission AML at the time of transplant proven via bone marrow aspiration and/or biopsy.
• o"Not in remission" is defined as "greater than 5.0% bone marrow blasts by aspirate morphology," as determined by a bone marrow aspirate obtained within 2 weeks of study registration.
• For primary induction failure patients: Patients must have failed at least 2 induction regimens.
• For patients with relapsed disease: Patients who relapse more than 6 months after preceding remission must fail at least one reinduction regimen to be eligible. For patients in whom the preceding remission is equal to or shorter than 6 months duration, no re-induction regimen is required to qualify for this protocol.
• If the pre-transplant bone marrow aspirate and biopsy are hypo plastic (less than 10% cellularity), and blast percentages cannot be determined, the patient is eligible if the preceding bone marrow met the above criteria.
• Patients with peripheral circulating blasts or patients with extramedullary leukemia are eligible if bone marrow aspirate and biopsy meets the above criteria.
• Karnofsky Performance Scale (KPS) above or equal to 70%
• Clinical laboratory values within the following parameters (repeat if more than 3 days before the first dose):
• Creatinine clearance ≥ 50 mL/min
• Hemoglobin \> 8 g/dL. Patients may be transfused to achieve this value.
• White blood cell (WBC) count \< 50,000/µL before administration of Pevonedistat on Cycle 1 Day 1. Note: Hydroxyurea may be used to control the level of circulating leukemic blast cell counts to not lower than 10,000/µL during the study.
• LFTs (ALT, AST) equal or less than 2.5 times upper limit of normal value.
• Bilirubin ≤ x 1.5 ULN limit
• Female patients who:

You may not qualify if:

• Treatment with any investigational products within 21 days of study registration.
• Known hypersensitivity to Azacitidine.
• Active uncontrolled infections or severe infectious disease, such as severe pneumonia, meningitis, or septicemia.
• Known central nervous system (CNS) involvement.
• Known human immunodeficiency virus (HIV) positivity.
• Known hepatitis B surface antigen-positive, or known active hepatitis C infection.
• Note: Patients who have isolated positive hepatitis B core antibody (ie, in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load. Patients who have positive hepatitis C antibody may be included if they have an undetectable hepatitis C viral load.
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of study procedures
• Major surgery within 14 days before the first dose of any study drug or a scheduled surgery during study period.
• Diagnosed or treated for another malignancy within 2 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non- melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone resection.
• Life-threatening illness unrelated to cancer.
• Patients with uncontrolled coagulopathy or bleeding disorder.
• Known hepatic cirrhosis or severe pre-existing hepatic impairment
• Known cardiopulmonary disease defined as:
• Unstable angina;

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead
• Millennium Pharmaceuticals, Inc.: collaborator
• Takeda: collaborator

Study Sites (1)

Penn State Hershey Medical Center: Penn State Cancer Institute

Hershey, Pennsylvania, 17033, United States

Location

Related Publications (5)

• Sierra J, Storer B, Hansen JA, Bjerke JW, Martin PJ, Petersdorf EW, Appelbaum FR, Bryant E, Chauncey TR, Sale G, Sanders JE, Storb R, Sullivan KM, Anasetti C. Transplantation of marrow cells from unrelated donors for treatment of high-risk acute leukemia: the effect of leukemic burden, donor HLA-matching, and marrow cell dose. Blood. 1997 Jun 1;89(11):4226-35.

  PMID: 9166868 BACKGROUND

• Giralt S, Estey E, Albitar M, van Besien K, Rondon G, Anderlini P, O'Brien S, Khouri I, Gajewski J, Mehra R, Claxton D, Andersson B, Beran M, Przepiorka D, Koller C, Kornblau S, Korbling M, Keating M, Kantarjian H, Champlin R. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood. 1997 Jun 15;89(12):4531-6.

  PMID: 9192777 BACKGROUND

• Saito T, Kanda Y, Kami M, Kato K, Shoji N, Kanai S, Ohnishi T, Kawano Y, Nakai K, Ogasawara T, Matsubara H, Makimoto A, Tanosaki R, Tobinai K, Wakasugi H, Takaue Y, Mineishi S. Therapeutic potential of a reduced-intensity preparative regimen for allogeneic transplantation with cladribine, busulfan, and antithymocyte globulin against advanced/refractory acute leukemia/lymphoma. Clin Cancer Res. 2002 Apr;8(4):1014-20.

  PMID: 11948108 BACKGROUND

• Kassim AA, Chinratanalab W, Ferrara JL, Mineishi S. Reduced-intensity allogeneic hematopoietic stem cell transplantation for acute leukemias: 'what is the best recipe?'. Bone Marrow Transplant. 2005 Oct;36(7):565-74. doi: 10.1038/sj.bmt.1705075.

  PMID: 15995714 BACKGROUND

• Slavin S, Nagler A, Naparstek E, Kapelushnik Y, Aker M, Cividalli G, Varadi G, Kirschbaum M, Ackerstein A, Samuel S, Amar A, Brautbar C, Ben-Tal O, Eldor A, Or R. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood. 1998 Feb 1;91(3):756-63.

  PMID: 9446633 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

pevonedistat; Transplantation; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Surgical Procedures, Operative; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Limitations and Caveats

limitations to the data exist as the sponsor closed the study prior to subjects meeting study endpoints.

Results Point of Contact

• Title: Michelle Stojanovic
• Organization: Penn State Cancer Institute

mstojanovic1@pennstatehealth.psu.edu

7175310003

Study Officials

• Shin Mineishi, MD

  Penn State Cancer Institute (Hershey Medical Center)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Director, Blood and Marrow Transplant Program

Study Record Dates

• First Submitted: July 26, 2018
• First Posted: October 17, 2018
• Study Start: July 18, 2018
• Primary Completion: July 22, 2019
• Study Completion: July 22, 2019
• Last Updated: December 16, 2020
• Results First Posted: October 29, 2020

Record last verified: 2020-11

Locations

US (1)