Acute Myeloid LeukemiaPhase 1/2NCT02614560
A Study of Vadastuximab Talirine Given Prior to or After Allogeneic Hematopoietic Stem Cell Transplant in AML Patients
A Phase 1/2 study testing Fludarabine, Melphalan and vadastuximab talirine in people with Acute Myeloid Leukemia, run by Seagen Inc. at 11 sites in United States.
Trial summary
This study will examine the safety and anti-leukemic profile of SGN-CD33A (vadastuximab talirine) in patients with relapsed chemo-resistant AML, who are given vadastuximab talirine in sequence with standard treatments before a planned stem cell transplant, or as maintenance therapy after a stem cell transplant. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Fludarabine, Melphalan and vadastuximab talirine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 11 sitesUnited States
- Study dates
- Nov 2015to 14 Sep 2017
- Phase
- Phase 1/2
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Relapsed/refractory acute myeloid leukemia (AML) except for acute promyelocytic leukemia
- Eastern Cooperative Oncology Group status of 0 or 1
- Adequate baseline renal and hepatic function
- For Pre-allo Part A (before stem cell transplant): Relapsed or refractory AML (greater than 5% blasts)
- For Pre-allo Part A (before stem cell transplant): Availability of an HLA matched related or unrelated donor
- For Pre-allo Part A (before stem cell transplant): Eligible for an allogeneic hematopoietic stem cell transplant
- For Post-allo Part B: Transplant must have been performed with active AML (greater than 5% blasts) using a conventional conditioning regimen and have achieved CR or CRi post-alloSCT (with ANC greater than or equal to 1,000 and platelet greater than or equal to 50,000)
- For Post-allo Part B: Treatment must begin at least 42 days, but no more than 100 days post-transplant.
Who cannot join
- Inadequate heart function
- Inadequate lung function
- Previous central nervous system leukemia
- Any history of another metastatic malignancy
- Anti-leukemia treatment within14 days of study drug (other than hydroxyurea or 6-mercaptopurine), immunosuppressive therapy (except for GVHD treatment/prophylaxis in Part B), or investigational agents
- For Pre-allo Part A (before stem cell transplant): Partially matched donors (related or unrelated) and umbilical cord blood cells are excluded as the source of hematopoietic stem cells
Show all 11Show fewer
- For Pre-allo Part A (before stem cell transplant): Prior alloSCT
- For Post-allo Part B: Active GVHD Grade 2 or higher
- For Post-allo Part B:History of veno-occlusive disease requiring defibrotide
- For Post-allo Part B: History of Grade 2 or higher hepatic GVHD
- For Post-allo Part B: Concurrent use of corticosteroids equivalent of prednisone at a dose of greater than 0.5 mg/kg
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
University of Chicago
Chicago, Illinois, 60637-1470
Case Western Reserve University / University Hospitals Case Medical Center
Cleveland, Ohio, 44106
Colorado Blood Cancer Institute
Denver, Colorado, 80218
City of Hope National Medical Center
Duarte, California, 91010-3000
MD Anderson Cancer Center / University of Texas
Houston, Texas, 77030-4095
Memorial Sloan Kettering Cancer Center
New York, New York, 10021
Weill Cornell Medical College
New York, New York, 10065
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109-1024
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612
University of Kansas Cancer Center
Westwood, Kansas, United States
About this study
Official title: A Phase 1/2 Study of Vadastuximab Talirine Administered in Sequence With Allogeneic Hematopoietic Stem Cell Transplant in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)
This study will examine the safety and anti-leukemic profile of SGN-CD33A (vadastuximab talirine) in patients with relapsed chemo-resistant AML, who are given vadastuximab talirine in sequence with standard treatments before a planned stem cell transplant, or as maintenance therapy after a stem cell transplant. The main purpose of the study is to find the best dose and determine the anti-leukemic activity of vadastuximab talirine, given either pre- or post-allogeneic stem cell transplant (alloSCT) for adults with relapsed or refractory AML. This will be determined by assessing the safety and tolerability of vadastuximab talirine. In addition, the pharmacokinetic profile and anti-leukemic activity of the study treatment will be assessed.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Fludarabine, Melphalan, vadastuximab talirine
- Keywords
- acute myeloid leukemia, AML, antibody-drug conjugate
- 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.
FludarabineDrug
30 mg/m2/day intravenously, 5 to 2 days before the transplant (total dose of 120 mg/m2)
MelphalanDrug
Melphalan 140 mg/m2 intravenously, 2 days before the transplant
vadastuximab talirineDrug
Pre-allo (before stem cell transplant) given 14 days before the stem cell transplant
vadastuximab talirineDrug
Post-allo (after stem cell transplant) given on Day 1 of each cycle
| Study group | Role | What they receive |
|---|---|---|
| Pre-allo (before stem cell transplant) | Experimental | Pre-allo reduced intensity chemotherapy vadastuximab talirine (melphalan and fludarabine) Receives: Drug: Fludarabine; Drug: Melphalan; Drug: vadastuximab talirine |
| Post-allo (after stem cell transplant) | Experimental | Post-allo vadastuximab talirine Receives: Drug: vadastuximab talirine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Adverse Events
AE: Adverse events; TEAE: Treatment-emergent adverse event. Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), v4.03. Grade 1 = mild, no intervention needed; Grade 2 = moderate, minimal intervention needed; Grade 3 = severe or medically significant, hospitalization is required; Grade 4 = life-threatening, urgent intervention needed; Grade 5 = death related to adverse event. An AE is considered serious if it was fatal, life threatening, required hospitalization, was disabling/incapacitating, resulted in a birth defect or congenital anomally, or was otherwise considered to be medically significant.
Measured: Approximately 1 year
Incidence of Laboratory Abnormalities
Number (count) of participants that experienced a Grade 3 or higher laboratory toxicity (hematology and chemistry). Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), v4.03. Grade 1 = mild, no intervention needed; Grade 2 = moderate, minimal intervention needed; Grade 3 = severe or medically significant, hospitalization is required; Grade 4 = life-threatening, urgent intervention needed; Grade 5 = death related to adverse event.
Measured: Approximately 1 year
1-year Survival Rate
1-year survival rate estimated using Kaplan-Meier methods The start date for overall survival is the day of alloSCT.
Measured: 12 months
Rate of MRD Negativity
Rate of MRD (minimal residual disease) negativity at Day -1 (1 day prior to transplant) and Day 30 post-transplant (Part A only)
Measured: 30 days
Secondary outcomes (3)
Best Response of CR or CRi
Percentage of patients who achieved a best response of CRi (complete remission with incomplete blood count recovery) or CR (complete remission)
Measured: 9 weeks
Duration of Response
Defined as the time from the start of the first documented complete response (CR) or complete remission with incomplete blood count recovery (CRi) to the documentation of relapse or death due to any cause.
Measured: 9 weeks
Overall Survival
Defined as the time from the day of alloSCT to the date of death due to any cause.
Measured: Approximately 96 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2015 (estimated)
- Study startNov 2015
- Primary completion10 Feb 2017
- Study completion14 Sep 2017
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 Acute Myeloid 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seagen Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Phillip Garfin, MD, PhD, Study director, Seagen Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02614560
- Sponsor's protocol ID
- SGN33A-003
- Status last verified
- Dec 2018
- First submitted
- 20 Nov 2015
- Last updated
- 9 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study of Vadastuximab Talirine Administered in Sequence With Allogeneic Hematopoietic Stem Cell Transplant in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)
- ClinicalTrials.gov ID
- NCT02614560
- Acronym / sponsor ID
- SGN33A-003
- Conditions
- Acute Myeloid Leukemia
- Keywords
- acute myeloid leukemia, AML, antibody-drug conjugate
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Seagen Inc.Industry (pharma, biotech, devices)
- Study start
- Nov 2015
- Primary completion
- 10 Feb 2017 (actual)
- Study completion
- 14 Sep 2017 (actual)
- First posted
- 25 Nov 2015 (estimated)
- Results
- Posted 9 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will examine the safety and anti-leukemic profile of SGN-CD33A (vadastuximab talirine) in patients with relapsed chemo-resistant AML, who are given vadastuximab talirine in sequence with standard treatments before a planned stem cell transplant, or as maintenance therapy after a stem cell transplant. The main purpose of the study is to find the best dose and determine the anti-leukemic activity of vadastuximab talirine, given either pre- or post-allogeneic stem cell transplant (alloSCT) for adults with relapsed or refractory AML. This will be determined by assessing the safety and tolerability of vadastuximab talirine. In addition, the pharmacokinetic profile and anti-leukemic activity of the study treatment will be assessed.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pre-allo (before stem cell transplant) | Experimental | Drug: Fludarabine, Drug: Melphalan, Drug: vadastuximab talirinePre-allo reduced intensity chemotherapy vadastuximab talirine (melphalan and fludarabine) |
| Post-allo (after stem cell transplant) | Experimental | Drug: vadastuximab talirinePost-allo vadastuximab talirine |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Relapsed/refractory acute myeloid leukemia (AML) except for acute promyelocytic leukemia
- Eastern Cooperative Oncology Group status of 0 or 1
- Adequate baseline renal and hepatic function
- For Pre-allo Part A (before stem cell transplant): Relapsed or refractory AML (greater than 5% blasts)
- For Pre-allo Part A (before stem cell transplant): Availability of an HLA matched related or unrelated donor
Key exclusion criteria (11 listed)
- Inadequate heart function
- Inadequate lung function
- Previous central nervous system leukemia
- Any history of another metastatic malignancy
- Anti-leukemia treatment within14 days of study drug (other than hydroxyurea or 6-mercaptopurine), immunosuppressive therapy (except for GVHD treatment/prophylaxis in Part B), or investigational agents
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 |
|---|---|---|
| Fludarabine30 mg/m2/day intravenously, 5 to 2 days before the transplant (total dose of 120 mg/m2) | Drug | Pre-allo (before stem cell transplant) |
| MelphalanMelphalan 140 mg/m2 intravenously, 2 days before the transplant | Drug | Pre-allo (before stem cell transplant) |
| vadastuximab talirinePre-allo (before stem cell transplant) given 14 days before the stem cell transplant | Drug | Pre-allo (before stem cell transplant) |
| vadastuximab talirinePost-allo (after stem cell transplant) given on Day 1 of each cycle | Drug | Post-allo (after stem cell transplant) |
Primary outcome
Incidence of Adverse Events
Time frame: Approximately 1 year
AE: Adverse events; TEAE: Treatment-emergent adverse event. Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), v4.03. Grade 1 = mild, no intervention needed; Grade 2 = moderate, minimal intervention needed; Grade 3 = severe or medically significant, hospitalization is required; Grade 4 = life-threatening, urgent intervention needed; Grade 5 = death related to adverse event. An AE is considered serious if it was fatal, life threatening, required hospitalization, was disabling/incapacitating, resulted in a birth defect or congenital anomally, or was otherwise considered to be medically significant.
Incidence of Laboratory Abnormalities
Time frame: Approximately 1 year
Number (count) of participants that experienced a Grade 3 or higher laboratory toxicity (hematology and chemistry). Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), v4.03. Grade 1 = mild, no intervention needed; Grade 2 = moderate, minimal intervention needed; Grade 3 = severe or medically significant, hospitalization is required; Grade 4 = life-threatening, urgent intervention needed; Grade 5 = death related to adverse event.
1-year Survival Rate
Time frame: 12 months
1-year survival rate estimated using Kaplan-Meier methods The start date for overall survival is the day of alloSCT.
Rate of MRD Negativity
Time frame: 30 days
Rate of MRD (minimal residual disease) negativity at Day -1 (1 day prior to transplant) and Day 30 post-transplant (Part A only)
3 secondary outcomes
Best Response of CR or CRi
Time frame: 9 weeks
Duration of Response
Time frame: 9 weeks
Overall Survival
Time frame: Approximately 96 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Phillip Garfin, MD, PhD study director
Seagen Inc.
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Fludarabine, Melphalan and vadastuximab talirine in people with Acute Myeloid Leukemia, run by Seagen Inc. at 11 sites 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 8 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 9 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites 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 combined 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.
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 9 Jan 2019). 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?
Incidence of Adverse Events (time frame: Approximately 1 year). The study lists 4 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 9 Jan 2019.