Acute Myeloid Leukemia (AML)Phase 2NCT03709576
Pevonedistat and Azacitidine as Maintenance Therapy After Allogeneic Stem Cell Transplantation for Non-Remission AML
A Phase 2 study testing Pevonedistat, transplant and Azacitidine in people with Acute Myeloid Leukemia (AML), run by Milton S. Hershey Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Acute Myeloid Leukemia (AML)
- What is being tested?
- Pevonedistat, transplant and Azacitidine
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Jul 2018to 22 Jul 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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:
- Are postmenopausal (see Appendix for definition) for at least 1 year before the screening visit, OR
- Are surgically sterile, OR
- If they are of childbearing potential:
- Agree to practice 1 highly effective method and 1 additional effective (barrier) method of contraception (see Appendix), at the same time, from the time of signing the informed consent through 4 months after the last dose of study drug (female and male condoms should not be used together), or
- Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post ovulation methods] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.)
- Male patients, even if surgically sterilized (i.e., status post vasectomy), who:
- Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug (female and male condoms should not be used together), or
- Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post ovulation methods for the female partner] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.)
- Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
Who cannot join
- 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.
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- 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;
- Congestive heart failure (New York Heart Association [NYHA] Class III or IV; see appendix);
- Myocardial infarction (MI) within 6 months prior to first dose (patients who had ischemic heart disease such as a (ACS), MI, and/or revascularization greater than 6 months before screening and who are without cardiac symptoms may enroll);
- Cardiomyopathy;
- Clinically significant arrhythmia:
- History of polymorphic ventricular fibrillation or torsade de pointes,
- Permanent atrial fibrillation [a fib], defined as continuous a fib for ≥ 6 months,
- Persistent a fib, defined as sustained a fib lasting > 7 days and/or requiring cardioversion in the 4 weeks before screening,
- Grade 3 a fib defined as symptomatic and incompletely controlled medically, or controlled with device (e.g. pacemaker), or ablation and
- Patients with paroxysmal a fib or < Gr 3 a fib for period of at least 6 months are permitted to enroll provided that their rate is controlled on a stable regimen.
- Implantable cardioverter defibrillator;
- Moderate to severe aortic and/or mitral stenosis or other valvulopathy (ongoing);
- Pulmonary hypertension
- Uncontrolled high blood pressure (i.e., systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg).
- Prolonged rate corrected QT (QTc) interval ≥ 500 msec, calculated according to institutional guidelines.
- Left ventricular ejection fraction (LVEF) < 50% as assessed by echocardiogram or radionuclide angiography.
- Known moderate to severe chronic obstructive pulmonary disease, interstitial lung disease, and pulmonary fibrosis.
- Systemic antineoplastic therapy or radiotherapy for other malignant conditions within 14 days before the first dose of any study drug, except for hydroxyurea.
- Female patients who are both lactating and breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before first dose of study drug.
- Female patients who intend to donate eggs (ova) during the course of this study or 4 months after receiving their last dose of study drug(s).
- Male patients who intend to donate sperm during the course of this study or 4 months after receiving their last dose of study drug(s).
- Patients who need to use clinically significant CYP3A enzyme inducers (listed on Appendix A)
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn State Hershey Medical Center: Penn State Cancer Institute
Hershey, Pennsylvania, 17033
About this study
Official title: A Phase II Study of Pevonedistat (MLN4924, TAK924) and Azacitidine as Maintenance Therapy After Allogeneic Stem Cell Transplantation for Non-Remission Acute Myelogenous Leukemia
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.
Read the detailed description
In preclinical studies Pevonedistat has shown significant single agent activity against mouse xenograft models of AML cell Line HL-60. Also this effect seemed to be synergistically enhanced by combining it with Azacitidine. In clinical arena, Pevonedistat has shown single agent activity in heavily pretreated patients with AML. In Study C15003, responses (complete responses [CRs] and partial responses [PRs]) were observed in a variety of patient settings, including post allogeneic transplant, therapy-related AML, and primary refractory AML, although some of the responses were of relatively short duration. Study C15009 is an ongoing phase 1b study evaluating the MTD of Pevonedistat on Days 1, 3, and 5 in combination with 75 mg/m2 Azacitidine (administered on a 5-on/2-off [weekend]/2-on schedule) in a 28-day treatment cycle in patients 60 years of age or older with treatment naïve AML who are unlikely to benefit from standard induction therapy. As of 22 June 2017, enrollment had completed and 15 patients remained on study. As of 22 January 2017, preliminary data are available for 64 patients enrolled in the study who received at least 1 dose of Pevonedistat in combination with Azacitidine; these patients had completed a total of approximately 360 cycles, with a median of 4 cycles of treatment In the dose escalation cohorts, 6 patients received 20 mg/m2 Pevonedistat, and 3 patients received 30 mg/m2. The most common events (reported by ≥ 25% of patients) were constipation (45%), nausea (42%), fatigue (39%), anemia (34%), febrile neutropenia (30%), decreased appetite (28%), and thrombocytopenia (27%). The MTD in this study was determined to be 20 mg/m2 Pevonedistat given on Days 1, 3, and 5, in combination with 75 mg/m2 Azacitidine given on Days 1 through 5, 8, and 9, in 28 day treatment cycles. A total of 45 (70%) patients experienced at least 1 SAE A total of 14 SAEs were reported for more than 1 patient, including: febrile neutropenia (16 patients); pneumonia (8 patients); pyrexia (4 patients); AML and sepsis (3 patients); and acute myocardial infarction, cellulitis, diverticulitis, dyspnea, embolism, hypoxia, mental status changes, multi-organ failure, and transaminase increased (2 patients each). A total of 19 patients treated with Pevonedistat (either 20 mg/m2 or 30 mg/m2), discontinued from Study participation because of a TEAE. No other events leading to discontinuation were assessed by study investigators as at least possibly related to study drug treatment. 11 on-study deaths had been reported; none assessed as related to study treatment. A total of 31 patients experienced PR or better. Eighteen patients had a best response of CR, 4 patients had a best response of CRi, and 9 patients had a best response of PR. One patient in the 30 mg/m2 dose level group achieved a CR; all other responses occurred in patients treated with 20 mg/m2.
The following studies are currently enrolling.
- Study 2001: A Phase 2, randomized, controlled Open-Label Clinical study of the efficacy and safety of Pevonedistat plus Azacitidine versus single-agent Azacitidine in patients with higher-risk myelodysplastic syndromes, chronic myelomonocytic leukemia and low-blast acute myelogenous leukemia.
- Study 1012: A phase 1/1b, Open-label Study of Pevonedistat (MLN4924, TAK-924) as Single Agent and in Combination with Azacitidine in adult East Asian patients with acute myeloid leukemia or myelodysplastic syndromes
Hence owing to the current knowledge of clinical and preclinical experience with Azacitidine and Pevonedistat alone and in combination, this combination appears feasible for testing in patients post-transplant with at very high risk of relapse.
The Investigator proposes a study using a combination of Pevonedistat and Azacitidine for maintenance therapy after allogeneic HSCT for non-remission. Patients will receive up to five 28 day cycles of the investigational maintenance therapy. Maintenance therapy will begin between days +30 to +45 post-transplant.
- Conditions
- Acute Myeloid Leukemia (AML)
- Being tested
- Pevonedistat, transplant, Azacitidine
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PevonedistatDrug
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.
transplantProcedure or surgery
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.
AzacitidineDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Pevonedistat; Procedure: transplant; Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
One Year Overall Survival Assessed by the Kaplan-Meier Plots
One year overall survival assess by Kaplan Meier Plots
Measured: 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.
Measured: 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
Measured: not analyzed
Secondary outcomes (6)
To Assess the Overall Disease Free Survival, Relapse, and GVHD After the Above Noted Treatment
overall disease free survival, relapse and GVHD unable to be determined as trial was closed by the sponsor prior to meeting this objective
Measured: not analyzed
One-year Disease-free Survival
One-year disease-free survival unable to be determined as trail was closed by the sponsor prior to meeting this endpoint
Measured: not analyzed
Cumulative Incidence of Relapse at 2 Years
Cumulative incidence of relapse at 2 years unable to be determined as trial was closed by the sponsor prior to meeting this objective
Measured: not analyzed
Two-year and Five-year Disease-free and Overall Survival
Two-year and five-year disease-free and overall survival unable to be determined as trial was closed by the sponsor prior to meeting this objective
Measured: not analyzed
Treatment Related Mortality/Morbidity
Treatment related mortality/morbidity unable to be determined as trial was closed by sponsor prior to meeting this objective
Measured: not analyzed
Incidence and Severity of Acute and Chronic GVHD
Incidence and severity of acute and chronic GVHD unable to be determined as trial was closed by sponsor prior to meeting this objective
Measured: not analyzed
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2018
- Study start18 Jul 2018
- Primary completion22 Jul 2019
- Study completion22 Jul 2019
Why it stopped: Funding pulled
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.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid Leukemia (AML)Studies of the same condition, open and under way.
- More trials run by Milton S. Hershey Medical CenterThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Milton S. Hershey Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc., Takeda
- Responsible party
- Principal investigator, Shin Mineishi, Milton S. Hershey Medical Center
- Investigators
- Shin Mineishi, MD, Principal investigator, Penn State Cancer Institute (Hershey Medical Center)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03709576
- Sponsor's protocol ID
- PSCI 17-056
- Status last verified
- Nov 2020
- First submitted
- 26 Jul 2018
- Last updated
- 16 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 9166868Giralt 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.
PubMed 9192777Saito 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.
PubMed 11948108Kassim 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.
PubMed 15995714Slavin 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.
PubMed 9446633
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Pevonedistat (MLN4924, TAK924) and Azacitidine as Maintenance Therapy After Allogeneic Stem Cell Transplantation for Non-Remission Acute Myelogenous Leukemia
- ClinicalTrials.gov ID
- NCT03709576
- Acronym / sponsor ID
- PSCI 17-056
- Conditions
- Acute Myeloid Leukemia (AML)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding pulled
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Milton S. Hershey Medical CenterUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc., Takeda
- Study start
- 18 Jul 2018 (actual)
- Primary completion
- 22 Jul 2019 (actual)
- Study completion
- 22 Jul 2019 (actual)
- First posted
- 17 Oct 2018 (actual)
- Results
- Posted 29 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
In preclinical studies Pevonedistat has shown significant single agent activity against mouse xenograft models of AML cell Line HL-60. Also this effect seemed to be synergistically enhanced by combining it with Azacitidine. In clinical arena, Pevonedistat has shown single agent activity in heavily pretreated patients with AML. In Study C15003, responses (complete responses [CRs] and partial responses [PRs]) were observed in a variety of patient settings, including post allogeneic transplant, therapy-related AML, and primary refractory AML, although some of the responses were of relatively short duration. Study C15009 is an ongoing phase 1b study evaluating the MTD of Pevonedistat on Days 1, 3, and 5 in combination with 75 mg/m2 Azacitidine (administered on a 5-on/2-off [weekend]/2-on schedule) in a 28-day treatment cycle in patients 60 years of age or older with treatment naïve AML who are unlikely to benefit from standard induction therapy. As of 22 June 2017, enrollment had completed and 15 patients remained on study. As of 22 January 2017, preliminary data are available for 64 patients enrolled in the study who received at least 1 dose of Pevonedistat in combination with Azacitidine; these patients had completed a total of approximately 360 cycles, with a median of 4 cycles of treatment In the dose escalation cohorts, 6 patients received 20 mg/m2 Pevonedistat, and 3 patients received 30 mg/m2. The most common events (reported by ≥ 25% of patients) were constipation (45%), nausea (42%), fatigue (39%), anemia (34%), febrile neutropenia (30%), decreased appetite (28%), and thrombocytopenia (27%). The MTD in this study was determined to be 20 mg/m2 Pevonedistat given on Days 1, 3, and 5, in combination with 75 mg/m2 Azacitidine given on Days 1 through 5, 8, and 9, in 28 day treatment cycles. A total of 45 (70%) patients experienced at least 1 SAE A total of 14 SAEs were reported for more than 1 patient, including: febrile neutropenia (16 patients); pneumonia (8 patients); pyrexia (4 patients); AML and sepsis (3 patients); and acute myocardial infarction, cellulitis, diverticulitis, dyspnea, embolism, hypoxia, mental status changes, multi-organ failure, and transaminase increased (2 patients each). A total of 19 patients treated with Pevonedistat (either 20 mg/m2 or 30 mg/m2), discontinued from Study participation because of a TEAE. No other events leading to discontinuation were assessed by study investigators as at least possibly related to study drug treatment. 11 on-study deaths had been reported; none assessed as related to study treatment. A total of 31 patients experienced PR or better. Eighteen patients had a best response of CR, 4 patients had a best response of CRi, and 9 patients had a best response of PR. One patient in the 30 mg/m2 dose level group achieved a CR; all other responses occurred in patients treated with 20 mg/m2.
The following studies are currently enrolling.
- Study 2001: A Phase 2, randomized, controlled Open-Label Clinical study of the efficacy and safety of Pevonedistat plus Azacitidine versus single-agent Azacitidine in patients with higher-risk myelodysplastic syndromes, chronic myelomonocytic leukemia and low-blast acute myelogenous leukemia.
- Study 1012: A phase 1/1b, Open-label Study of Pevonedistat (MLN4924, TAK-924) as Single Agent and in Combination with Azacitidine in adult East Asian patients with acute myeloid leukemia or myelodysplastic syndromes
Hence owing to the current knowledge of clinical and preclinical experience with Azacitidine and Pevonedistat alone and in combination, this combination appears feasible for testing in patients post-transplant with at very high risk of relapse.
The Investigator proposes a study using a combination of Pevonedistat and Azacitidine for maintenance therapy after allogeneic HSCT for non-remission. Patients will receive up to five 28 day cycles of the investigational maintenance therapy. Maintenance therapy will begin between days +30 to +45 post-transplant.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pevonedistat and Azacitidine | Experimental | Drug: Pevonedistat, Procedure: transplant, Drug: AzacitidineThe 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- 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.
- 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):
Key exclusion criteria (36 listed)
- 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.
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 |
|---|---|---|
| PevonedistatTo 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. | Drug | Pevonedistat and Azacitidine |
| transplantAlthough 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. | Procedure or surgery | Pevonedistat and Azacitidine |
| AzacitidineTo 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. | Drug | Pevonedistat and Azacitidine |
Primary outcome
One Year Overall Survival Assessed by the Kaplan-Meier Plots
Time frame: 1 year
One year overall survival assess by Kaplan Meier Plots
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.
Time frame: not analyzed
Toxicity and efficacy unable to be determined as trial was closed by the sponsor prior to meeting this objective.
Toxicity Related to Pevonedistat
Time frame: not analyzed
Toxicity related to Pevonedistat unable to be determined as trial was closed by sponsor prior to meeting this objective
6 secondary outcomes
To Assess the Overall Disease Free Survival, Relapse, and GVHD After the Above Noted Treatment
Time frame: not analyzed
One-year Disease-free Survival
Time frame: not analyzed
Cumulative Incidence of Relapse at 2 Years
Time frame: not analyzed
Two-year and Five-year Disease-free and Overall Survival
Time frame: not analyzed
Treatment Related Mortality/Morbidity
Time frame: not analyzed
Incidence and Severity of Acute and Chronic GVHD
Time frame: not analyzed
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 9166868Sierra 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.
- Background: PubMed 9192777Giralt 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.
- Background: PubMed 11948108Saito 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.
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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.
Shin Mineishi, MD principal investigator
Penn State Cancer Institute (Hershey Medical Center)
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 Pevonedistat, transplant and Azacitidine in people with Acute Myeloid Leukemia (AML), run by Milton S. Hershey Medical Center 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 24 inclusion and 36 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 16 Dec 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 29 Oct 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?
One Year Overall Survival Assessed by the Kaplan-Meier Plots (time frame: 1 year). The study lists 3 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 NCT03709576, which also lists 5 linked publications.
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 16 Dec 2020.