LeukemiaPhase 1NCT02141828
A Phase 1 Dose Escalation and Expanded Cohort Study of EPZ-5676 in the Treatment of Pediatric Patients With Relapsed/Refractory Leukemias Bearing a Rearrangement of the MLL Gene
A Phase 1 study testing EPZ-5676 in people with Leukemia and Acute Myeloid Leukemia, run by Epizyme, Inc. at 9 sites in 2 countries.
Trial summary
A subset of patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) harbor rearrangements of the MLL gene, which are detected either by cytogenetic or fluorescent in situ hybridization evaluation at the time of diagnosis. Read more about this study
- Who is it for?
- Ages 3 months to 18 years
- Conditions the study is for
- Leukemia, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia
- What is being tested?
- EPZ-5676
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 9 sitesin 2 countries
- Study dates
- May 2014to Jun 2016
- Phase
- Phase 1
- 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 3 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age: >3 months to <18 years of age.
- Diagnosis: Patients must have documented relapsed/refractory ALL, AML, or acute leukemia of ambiguous lineage and meet the following criteria:
- Patients must have at least received an appropriate induction therapy regimen. Patients with persistent leukemia after induction therapy, or with recurrence of leukemia at any time during the course of treatment (including allogeneic HSCT) are eligible;
- Patients must have > 10% leukemic blasts in the bone marrow;
- Patients must have rearrangement involving the MLL gene, including reciprocal chromosomal translocations involving 11q23 by FISH, cytogenetic analysis, polymerase chain reaction (PCR) or next-generation sequencing (NGS) OR partial tandem duplication (PTD) of MLL by PCR or NGS.
- Therapeutic Options: Patients must be ineligible or inappropriate for other treatment regimens known to have curative potential.
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- Performance Level: Karnofsky > 50% for pts > 12 years; Lansky > 50% for pts < 12 years of age.
- Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
- Myelosuppressive Chemotherapy:
- 14 days must have elapsed since the completion of cytotoxic therapy
- Patients may receive hydroxyurea, low-dose cytarabine and/or glucocorticoids to control peripheral blood leukemic cell counts at study entry
- At least 7 days since the completion of therapy with hematopoietic growth factors
- At least 7 days since the completion of therapy with a biologic agent
- At least 21 days since receipt of chimeric antigen receptor therapy or other modified T cell therapy
- At least 60 days from prior total body irradiation (TBI)
- At least 60 days must have elapsed from hematopoietic stem cell transplantation (HSCT)
- Renal and Hepatic Function: Patient must have adequate renal and hepatic functions as indicated by the following laboratory values:
- Patient must have a calculated creatinine clearance or radioisotope GFR > 60mL/min/1.73m2 or a normal serum creatinine based on age/gender
- Total bilirubin < 1.5 x ULN for age or normal conjugated bilirubin
- ALT and AST < 3 x ULN (unless attributed to leukemic involvement)
- Cardiac Function: Patient must have a shortening fraction (SF) of > 27% or an ejection fraction (EF) of > 50% by echocardiogram or MUGA scan.
Who cannot join
- Patients with CNS 3 disease or symptomatic CNS disease
- Clinically active heart disease including prolonged QTc or prolonged PR interval, or history of arrhythmias
- On immunosuppressive or other anti-leukemic therapy, excluding patients receiving glucocorticoids for management of circulating blast count or patients on a stable dose (<20mg/m2/day prednisone or equivalent) of systemic or topical glucocorticoid therapy with ≤ Grade 1 GvHD or tapering dose of calcineurin inhibitor
- Patients with known bleeding diathesis or prothrombin time (PT) or aPTT >1.5 x ULN or fibrinogen <0.5 x LLN
- Receiving prophylactic use of hematopoietic colony stimulating factors
- Known history of infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HBsAg positive) or hepatitis C virus (anti-HCV positive)
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- Being actively treated for another concurrent malignancy
- Pregnant or nursing females;
- Male patients not willing to use a condom
- Uncontrolled intercurrent illness including, but not limited to uncontrolled infection, significant graft-versus-host-disease (GvHD) (Grade 2-4), or psychiatric illness/social situations that would limit compliance with study requirements
- Patients who are concurrently receiving strong inducers/inhibitors of CYP3A
- Patients with known history of Trisomy 21 (Down Syndrome), history of congenital immunodeficiency or inherited marrow failure disorder.
- Patients with known bleeding diathesis, or PT (Prothrombin time) or aPTT (activated partial thromboplastin time) > 1.5x ULN or <0.5x LLN.
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
United States8 sites
Emory Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
Children's Hospital Colorado
Aurora, Colorado, 80045
Johns Hopkins University
Baltimore, Maryland, 21287
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Childrens Hospital Los Angeles
Los Angeles, California, 90027
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
University of California San Francisco Medical Center-Parnassus
San Francisco, California, 94143
About this study
A subset of patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) harbor rearrangements of the MLL gene, which are detected either by cytogenetic or fluorescent in situ hybridization evaluation at the time of diagnosis. A protein called DOT1L plays an important role in the malignant process in these leukemias. EPZ-5676 is a molecule that blocks the activity of DOT1L, and is therefore being evaluated in the treatment of patients with MLL-rearranged leukemias.
Read the detailed description
This is a Phase 1b study of EPZ-5676 in pediatric patients. The study will have two phases. The first phase will assess escalating doses of EPZ-5676 in order to determine the maximally tolerated dose (MTD) or recommended phase 2 dose (RP2D) of EPZ-5676 as a 28-day continuous IV infusion. Once the MTD and/or RP2D is established, a second phase of the study will further evaluate the safety of EPZ-5676 and assess the anti-leukemia activity.
- Being tested
- EPZ-5676
- Keywords
- Leukemia, Advanced hematologic malignancies, Epizyme, Phase 1b, MLL gene, 11q23, Ambiguous lineage, ALL, AML, Acute leukemias, MLL-r
- Medical subject headings
- Leukemia, 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.
EPZ-5676Drug
Also called EPZ5676, DOT1L
28-day continuous IV infusion of each 28-day cycle, given until disease progression or unacceptable toxicity develops.
| Study group | Role | What they receive |
|---|---|---|
| EPZ-5676 | Experimental | EPZ-5676 Dose escalation and expansion cohorts Receives: Drug: EPZ-5676 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of EPZ-5676.
To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of EPZ-5676 as determined by incidence of protocol-specified dose-limiting adverse events.
Measured: 12 months
To assess the safety and tolerability of EPZ-5676 administered as a continuous intravenous (CIV) infusion
Safety and tolerability will be assessed by the incidence of adverse events in patients treated with EPZ-5676 and the evaluation of adverse events, vital signs, physical examination, 12-lead ECG, and laboratory assessments.
Measured: 22 months
Secondary outcomes (2)
Determine the pharmacokinetic (PK) and pharmacodynamic (PD) profile of EPZ-5676
The pharmacokinetic (PK) profile will include the analysis of Cmax, AUC and steady state concentration of EPZ-5676.
The pharmacodynamic (PD) profile will assess the effects of EPZ-5676 in peripheral blood mononuclear (PBMC) and bone marrow cells.
Measured: 18 months
Evaluate early evidence of anti-tumor activity
Anti-tumor activity will be assessed by objective response (OR) in pediatric patients
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2014 (estimated)
- Study startMay 2014
- Primary completionMay 2016
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Epizyme, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Celgene Corporation
- Responsible party
- Sponsor
- Investigators
- Neal Shukla, MD, Principal investigator, Memorial Sloan Kettering Cancer CenterLia Gore, MD, Principal investigator, Children's Hospital ColoradoPat Brown, MD, Principal investigator, Johns Hopkins UniversityLewis Silverman, MD, Principal investigator, Dana FarberMaureen O'Brien, MD, Principal investigator, Children's Hospital Medical Center, CincinnatiJim A Whitlock, MD, Principal investigator, Hospital of Sick KidsCynthia Wetmore, MD PhD, Principal investigator, Emory Children's Healthcare of AtlantaMignon Loh, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02141828
- Sponsor's protocol ID
- EPZ-5676-12-002
- Status last verified
- May 2020
- First submitted
- 11 May 2014
- Last updated
- 18 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Dose Escalation and Expanded Cohort Study of EPZ-5676 in the Treatment of Pediatric Patients With Relapsed/Refractory Leukemias Bearing a Rearrangement of the MLL Gene
- ClinicalTrials.gov ID
- NCT02141828
- Acronym / sponsor ID
- EPZ-5676-12-002
- Keywords
- Leukemia, Advanced hematologic malignancies, Epizyme, Phase 1b, MLL gene, 11q23, Ambiguous lineage, ALL
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Epizyme, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Celgene Corporation
- Study start
- May 2014
- Primary completion
- May 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 20 May 2014 (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 subset of patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) harbor rearrangements of the MLL gene, which are detected either by cytogenetic or fluorescent in situ hybridization evaluation at the time of diagnosis. A protein called DOT1L plays an important role in the malignant process in these leukemias. EPZ-5676 is a molecule that blocks the activity of DOT1L, and is therefore being evaluated in the treatment of patients with MLL-rearranged leukemias.
Detailed description
This is a Phase 1b study of EPZ-5676 in pediatric patients. The study will have two phases. The first phase will assess escalating doses of EPZ-5676 in order to determine the maximally tolerated dose (MTD) or recommended phase 2 dose (RP2D) of EPZ-5676 as a 28-day continuous IV infusion. Once the MTD and/or RP2D is established, a second phase of the study will further evaluate the safety of EPZ-5676 and assess the anti-leukemia activity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| EPZ-5676 | Experimental | Drug: EPZ-5676EPZ-5676 Dose escalation and expansion cohorts |
Who may qualify
- Ages
- 3 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (21 listed)
- Age: >3 months to <18 years of age.
- Diagnosis: Patients must have documented relapsed/refractory ALL, AML, or acute leukemia of ambiguous lineage and meet the following criteria:
- Therapeutic Options: Patients must be ineligible or inappropriate for other treatment regimens known to have curative potential.
- Performance Level: Karnofsky > 50% for pts > 12 years; Lansky > 50% for pts < 12 years of age.
- Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
Key exclusion criteria (13 listed)
- Patients with CNS 3 disease or symptomatic CNS disease
- Clinically active heart disease including prolonged QTc or prolonged PR interval, or history of arrhythmias
- On immunosuppressive or other anti-leukemic therapy, excluding patients receiving glucocorticoids for management of circulating blast count or patients on a stable dose (<20mg/m2/day prednisone or equivalent) of systemic or topical glucocorticoid therapy with ≤ Grade 1 GvHD or tapering dose of calcineurin inhibitor
- Patients with known bleeding diathesis or prothrombin time (PT) or aPTT >1.5 x ULN or fibrinogen <0.5 x LLN
- Receiving prophylactic use of hematopoietic colony stimulating factors
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 |
|---|---|---|
| EPZ-5676Also: EPZ5676, DOT1L28-day continuous IV infusion of each 28-day cycle, given until disease progression or unacceptable toxicity develops. | Drug | EPZ-5676 |
Primary outcome
Determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of EPZ-5676.
Time frame: 12 months
To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of EPZ-5676 as determined by incidence of protocol-specified dose-limiting adverse events.
To assess the safety and tolerability of EPZ-5676 administered as a continuous intravenous (CIV) infusion
Time frame: 22 months
Safety and tolerability will be assessed by the incidence of adverse events in patients treated with EPZ-5676 and the evaluation of adverse events, vital signs, physical examination, 12-lead ECG, and laboratory assessments.
2 secondary outcomes
Determine the pharmacokinetic (PK) and pharmacodynamic (PD) profile of EPZ-5676
Time frame: 18 months
Evaluate early evidence of anti-tumor activity
Time frame: 18 months
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 18 Jun 2023.
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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.
Neal Shukla, MD principal investigator
Memorial Sloan Kettering Cancer Center
Lia Gore, MD principal investigator
Children's Hospital Colorado
Pat Brown, MD principal investigator
Johns Hopkins University
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing EPZ-5676 in people with Leukemia and Acute Myeloid Leukemia, run by Epizyme, Inc. at 9 sites in 2 countries.
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 21 inclusion and 13 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 18 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Canada. 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 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.
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?
Determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of EPZ-5676. (time frame: 12 months). 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?
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 18 Jun 2023.