Acute Myeloid LeukemiaNCT01385787
MRD Testing Before and After Hematopoietic Cell Transplantation for Pediatric Acute Myeloid Leukemia
An observational study of Acute Myeloid Leukemia, run by Center for International Blood and Marrow Transplant Research at 38 sites in 2 countries.
Trial summary
This is a non-therapeutic study. Pediatric AML patients undergoing HCT with a myeloablative preparative regimen may be enrolled. Subjects can be enrolled 10-40 days prior to HCT. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Acute Myeloid Leukemia
- How many people
- 150 participants
- Where
- 38 sitesin 2 countries
- Study dates
- Oct 2011to May 2017
- Phase
- Observational
- 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 Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Participating institutions (transplant centers)
Who may be able to join
- Subject or legal guardian to understand and voluntarily sign an informed consent.
- Age 0-21 at time of transplant.
- Karnofsky score ≥ 70% (age ≥ 16 years old), or Lansky score ≥ 70% (age<16 years old).
- Patients with adequate physical function as measured by:
- Cardiac: Left ventricular ejection fraction at rest must be > 40%, or shortening fraction > 26%
- Hepatic: Bilirubin ≤ 2.5 mg/dL; and ALT, AST and Alkaline Phosphatase≤ 5 x ULN
Show all 35Show fewer
- Renal: Serum creatinine within normal range for age, or if serum creatinine outside normal range for age, then renal function (creatinine clearance or GFR) > 70 mL/min/1.73 m2.
- Pulmonary: DLCO, FEV1, FVC (diffusion capacity) > 50% of predicted (corrected for hemoglobin); if unable to perform pulmonary function tests, then O2 saturation > 92% in room air.
- Acute myelogenous leukemia (AML) at the following stages:
- High risk first complete remission (CR1), defined as:
- Having preceding myelodysplasia (MDS) -or-
- Diagnostic high risk karyotypes: del (5q) -5, -7, abn (3q), t (6;9), abnormalities of 12, t (9:22), complex karyotype (≥3 abnormalities), the presence of a high FLT3 ITD-AR (> 0.4) -or-
- Having >15% bone marrow blasts after 1st cycle and/or >5% after 2nd cycle before achieving CR -and-
- <5% blasts in the bone marrow, with peripheral ANC>500
- Intermediate risk first complete remission (CR1), defined as:
- Diagnostic karyotypes that are neither high-risk (as defined above) nor low risk (inv(16)/t(16:16); t(8;21); t(15;17)). Included are cases where cytogenetics could not be performed. -and-
- <5% blasts in the bone marrow, with peripheral ANC>500
- High risk based upon COG AAML 1031 criteria:
- High allelic ratio FLT3/ITD+, monosomy 7, del(5q) with any MRD status or standard risk cytogenetics with positive MRD at end of Induction I.
- <5% blasts in the bone marrow, with peripheral ANC>500
- Second or greater CR
- <5% blasts in the bone marrow, with peripheral ANC>500
- Therapy-related AML at any stage
- Prior malignancy in remission for >12 months.
- <5% blasts in the bone marrow, with peripheral ANC>500
- Myeloablative preparative regimen, defined as a regimen including one of the following as a backbone agent*:
- Busulfan ≥ 9mg/kg total dose (IV or PO). PK-based dosing is allowed, if intent is myeloablative dosing OR
- Total Body Irradiation≥1200cGy fractionated OR
- Treosulfan ≥ 42g/m2 total dose IV *Regimens may include secondary agents such as, but not limited to Ara-C, Fludarabine, VP-16. Regimens that combine Busulfan and TBI or treosulfan and TBI are allowed as long as the Busulfan or treosulfan meets or exceeds the dose listed and the TBI is below the dose listed.
- Graft source:
- HLA-identical sibling PBSC, BM, or cord blood
- Adult related or unrelated donor PBSC or BM matched at the allelic level for HLA-A, HLA-B, HLA-C, and HLA-DRB1 with no greater than a single antigen mismatch.
- One or two unrelated cord blood units:
- HLA≥4:6 at the low resolution level for HLA-A, HLA-B, at high resolution level at HLA-DRB1 for one or both units.
- If one unit, must have TNC≥2.5x107/kg; if two units, combination of the two must have TNC≥2.5x107/kg
Who cannot join
- Women who are pregnant (positive HCG) or breastfeeding.
- Evidence of HIV infection or HIV positive serology.
- Positive viral load (PCR) for Hepatitis B or C (negative serology, surface antigen, and core antibody may substitute for PCR).
- Current uncontrolled bacterial, viral or fungal infection (currently taking medication and progression of clinical symptoms).
- Autologous transplant < 12 months prior to enrollment.
- Prior allogeneic hematopoietic stem cell transplant.
Trial locations and contacts
38 sites in 2 countries.
38 sites in 2 countries
United States34 sites
University of Michigan
Ann Arbor, Michigan, 48109
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
The Children's Hospital Colorado
Aurora, Colorado, 80045
Johns Hopkins
Baltimore, Maryland, 21287
The Children's Hospital of Alabama, University of Alabama at Birmingham
Birmingham, Alabama, 35233
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Roswell Park Cancer Institute
Buffalo, New York, 14263
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
Medical University of South Carolina
Charleston, South Carolina, 29425
Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
University Hospitals of Cleveland Case Medical Ctr
Cleveland, Ohio, 44106
Cleveland Clinic
Cleveland, Ohio, 44195
Children's Hospital of Michigan
Detroit, Michigan, 48201
Duke University Medical Center
Durham, North Carolina, 27705
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
Riley Hospital for Children/Indiana University
Indianapolis, Indiana, 46202
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Loma Linda University
Loma Linda, California, 92354
University of Louisville
Louisville, Kentucky, 40202
Miami Children's Hospital
Miami, Florida, 33155
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Mount Sinai School of Medicine
New York, New York, 10029
Columbia University - The Morgan Stanley Children's Hospital of New York
New York, New York, 10032
Phoenix Children's Hospital
Phoenix, Arizona, 85016
Oregon Health & Sciences University - Doerbecher Children's
Portland, Oregon, 97239
Virginia Commonwealth University
Richmond, Virginia, 23219
University of Utah - Primary Children's Medical Center
Salt Lake City, Utah, 84108
Methodist Children's Hospital of South Texas/Texas Institute of Medicine and Surgery
San Antonio, Texas, 78229
University of California San Francisco
San Francisco, California, 94143
Washington University, St. Louis Children's Hospital
St Louis, Missouri, 63110
All Children's Hospital
St. Petersburg, Florida, 33701
New York Medical College
Valhalla, New York, 10595
Children's National Medical Center
Washington D.C., District of Columbia, 20910
Canada4 sites
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8
The Montreal Children's Hospital
Montreal, Quebec, H3H 1P3
Hopital Ste. Justine
Montreal, Quebec, H3T 1C5
Children's & Women's Health Centre of British Columbia
Vancouver, British Columbia, V6T 1Z3
About this study
Official title: The Role of Minimal Residual Disease Testing Before and After Hematopoietic Cell Transplantation for Pediatric Acute Myeloid Leukemia
This is a non-therapeutic study. Pediatric AML patients undergoing HCT with a myeloablative preparative regimen may be enrolled. Subjects can be enrolled 10-40 days prior to HCT. Three samples for MRD (measured by WT1 PCR and flow cytometry) will be collected from peripheral blood and bone marrow: 1) pre-HCT (<3 weeks prior to starting the preparative regimen), 2) day 42 +/- 14 days post HCT (early post-engraftment), and 3) day 100 (+/-20 days) post HCT. For two years after transplant, the subject's follow-up data will be collected using the Research Level Forms in the CIBMTR Forms Net internet data entry system. The main objective is to determine whether there is any association between level of pre-transplant and post-transplant bone marrow MRD using WT1 and flow cytometry with 2-year event-free-survival, and to estimate the strength of that association in terms of the predictive accuracy of MRD. The investigators hypothesize that measurable MRD at either time point will be associated with decreased 2-year event-free survival.
Read the detailed description
This is a prospective, non-therapeutic study, assessing the significance of minimal residual disease (MRD) at three different time points in relation to allogeneic HCT for pediatric AML. The study is a collaboration between the Pediatric Blood and Marrow Transplant Consortium (PBMTC) and the Resource for Clinical Investigations in Blood and Marrow Transplantation (RCI-BMT) of the Center for International Blood and Marrow Transplant Research (CIBMTR). The study will enroll pediatric AML patients who undergo myeloablative HCT at PBMTC sites. The eligibility criteria for this non-therapeutic study mirror widely accepted criteria for allogeneic HCT in pediatric AML.
The study tests the hypothesis that assessment of pre-transplant and post-transplant MRD predicts 2-year outcomes following transplant. Two MRD methodologies are being studied: flow cytometry and WT1 PCR. The secondary hypothesis is that combining these 2 methodologies will improve the accuracy in predicting 2-year outcomes following transplant.
It is well established that the level of minimal residual disease (MRD) during chemotherapy is a strong predictor of relapse in children with acute lymphoblastic leukemia (ALL) [33, 34]. Within this population, MRD levels have the potential to predict those patients who will respond well to standard therapy, thus allowing clinicians to tailor therapy and minimize toxicity while ensuring maximal cure rates [10]. MRD levels before allogeneic hematopoietic stem cell transplantation (HCT) also predict the risk of relapse post-HCT [25], leading to the clinical practice of reducing MRD levels as much as possible before transplant. By contrast, in children with acute myeloid leukemia (AML), the prognostic value of MRD levels prior to HCT remains unclear.
Our long-term objective is to improve the cure rate for children with AML. The investigators hypothesize that MRD levels before HCT will provide a powerful tool to select the best candidates for transplant, guide decision making in stem cell source and preparative therapy, and optimize the timing of the transplant. Measurements of MRD post-HCT will allow informed decisions about withdrawal of immunosuppressive therapy, administration of donor lymphocyte infusions, or alternative targeted therapies.
- Conditions
- Acute Myeloid Leukemia
- Keywords
- Pediatric (ages 0-21 years), myeloablative HCT, PBMTC sites
- Medical subject headings
- Leukemia, Myeloid, Acute
What is being measured
The primary outcome is the main question the study is designed to answer.
Two-year Event Free Survival (EFS)
Event-free survival is defined as the time from HCT to relapse, death, initiation of post-HCT therapy to treat AML relapse, loss to follow up or end of study whichever comes first.
Measured: 2 years post-HCT
Secondary outcomes (8)
Two-year overall survival (OS)
Overall survival is the time from HCT to death from any cause, loss to follow up or end of study, whichever comes first.
Measured: 2 years post-HCT
Disease relapse at 2 years
Relapse includes morphologic reappearance of leukemia or treatment for impending relapse. Death in remission is a competing risk. Relapse is defined as in 3.1. Cytogenetic or molecular relapse with <5% leukemic blasts in the bone marrow does not constitute a relapse unless unplanned AML-directed therapy is administered.
Measured: 2 years post-HCT
Occurrence of acute grade II-IV and grade III-IV GVHD by 200 days post-HCT
Any skin, gastrointestinal or liver abnormalities fulfilling the consensus criteria [36] of grades II-IV or grades III-IV acute GVHD are considered events. Death and second transplants are competing risks, and patients alive without acute GVHD will be censored at the time of last follow-up.
Measured: 200 days post-HCT
Occurrence of chronic GVHD at 2 years post-HCT
Occurrence of any symptoms in any organ system fulfilling the CIBMTR criteria of limited or extensive chronic GVHD. Death and the second transplant are competing risks, and patients alive without chronic GVHD will be censored at time of last follow-up.
Measured: 2 years post-HCT
Time to neutrophil engraftment
1st consecutive day of a sustained ANC ≥ 500/ μL for 3 consecutive days. Death without engraftment and second transplants are considered competing risks.
Measured: 42 days post-HCT
Time to platelet engraftment
1st day of platelet count ≥20,000/μL that persists ≥7 days, without transfusion. Death without engraftment and second transplants are considered competing risks.
Measured: 42 days post-HCT
Veno-occlusive Disease
Cumulative incidence of veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS), with median maximum bilirubin for subjects diagnosed with VOD/SOS. Subjects classified as having had VOD/SOS must meet the Jones Criteria, defined as: bilirubin>2mg/dL and at least 2 of the following signs: a) hepatomegaly and/or right upper quadrant pain, and b) >5% weight gain.
Measured: 2 years post-HCT
Chimerism
Whole blood chimerism and T-cell chimerism will be classified according to full (>95%), mixed (5-95%), or none (<5%) at 100 days.
Measured: 100 days post-HCT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2011 (estimated)
- Study startOct 2011
- Primary completionMay 2017
- Study completionMay 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Center for International Blood and Marrow Transplant Research
- Sponsor type
- Research network
- Collaborators
- Pediatric Blood and Marrow Transplant Consortium, St. Baldrick's Foundation, Otsuka Pharmaceutical Development & Commercialization, Inc.
- Responsible party
- Sponsor
- Investigators
- David A. Jacobsohn, MD, ScM, Principal investigator, Children's National Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01385787
- Sponsor's protocol ID
- 09-MRD
- Status last verified
- Sep 2017
- First submitted
- 28 Jun 2011
- Last updated
- 7 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Minimal Residual Disease Testing Before and After Hematopoietic Cell Transplantation for Pediatric Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT01385787
- Acronym / sponsor ID
- 09-MRD
- Conditions
- Acute Myeloid Leukemia
- Keywords
- Pediatric (ages 0-21 years), myeloablative HCT, PBMTC sites
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Center for International Blood and Marrow Transplant ResearchResearch network
- Collaborators
- Pediatric Blood and Marrow Transplant Consortium, St. Baldrick's Foundation, Otsuka Pharmaceutical Development & Commercialization, Inc.
- Study start
- Oct 2011 (actual)
- Primary completion
- May 2017 (actual)
- Study completion
- May 2017 (actual)
- First posted
- 30 Jun 2011 (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.
This is a non-therapeutic study. Pediatric AML patients undergoing HCT with a myeloablative preparative regimen may be enrolled. Subjects can be enrolled 10-40 days prior to HCT. Three samples for MRD (measured by WT1 PCR and flow cytometry) will be collected from peripheral blood and bone marrow: 1) pre-HCT (<3 weeks prior to starting the preparative regimen), 2) day 42 +/- 14 days post HCT (early post-engraftment), and 3) day 100 (+/-20 days) post HCT. For two years after transplant, the subject's follow-up data will be collected using the Research Level Forms in the CIBMTR Forms Net internet data entry system. The main objective is to determine whether there is any association between level of pre-transplant and post-transplant bone marrow MRD using WT1 and flow cytometry with 2-year event-free-survival, and to estimate the strength of that association in terms of the predictive accuracy of MRD. The investigators hypothesize that measurable MRD at either time point will be associated with decreased 2-year event-free survival.
Detailed description
This is a prospective, non-therapeutic study, assessing the significance of minimal residual disease (MRD) at three different time points in relation to allogeneic HCT for pediatric AML. The study is a collaboration between the Pediatric Blood and Marrow Transplant Consortium (PBMTC) and the Resource for Clinical Investigations in Blood and Marrow Transplantation (RCI-BMT) of the Center for International Blood and Marrow Transplant Research (CIBMTR). The study will enroll pediatric AML patients who undergo myeloablative HCT at PBMTC sites. The eligibility criteria for this non-therapeutic study mirror widely accepted criteria for allogeneic HCT in pediatric AML.
The study tests the hypothesis that assessment of pre-transplant and post-transplant MRD predicts 2-year outcomes following transplant. Two MRD methodologies are being studied: flow cytometry and WT1 PCR. The secondary hypothesis is that combining these 2 methodologies will improve the accuracy in predicting 2-year outcomes following transplant.
It is well established that the level of minimal residual disease (MRD) during chemotherapy is a strong predictor of relapse in children with acute lymphoblastic leukemia (ALL) [33, 34]. Within this population, MRD levels have the potential to predict those patients who will respond well to standard therapy, thus allowing clinicians to tailor therapy and minimize toxicity while ensuring maximal cure rates [10]. MRD levels before allogeneic hematopoietic stem cell transplantation (HCT) also predict the risk of relapse post-HCT [25], leading to the clinical practice of reducing MRD levels as much as possible before transplant. By contrast, in children with acute myeloid leukemia (AML), the prognostic value of MRD levels prior to HCT remains unclear.
Our long-term objective is to improve the cure rate for children with AML. The investigators hypothesize that MRD levels before HCT will provide a powerful tool to select the best candidates for transplant, guide decision making in stem cell source and preparative therapy, and optimize the timing of the transplant. Measurements of MRD post-HCT will allow informed decisions about withdrawal of immunosuppressive therapy, administration of donor lymphocyte infusions, or alternative targeted therapies.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Participating institutions (transplant centers)
Key inclusion criteria (35 listed)
- Subject or legal guardian to understand and voluntarily sign an informed consent.
- Age 0-21 at time of transplant.
- Karnofsky score ≥ 70% (age ≥ 16 years old), or Lansky score ≥ 70% (age<16 years old).
- Patients with adequate physical function as measured by:
- Acute myelogenous leukemia (AML) at the following stages:
Key exclusion criteria (6 listed)
- Women who are pregnant (positive HCG) or breastfeeding.
- Evidence of HIV infection or HIV positive serology.
- Positive viral load (PCR) for Hepatitis B or C (negative serology, surface antigen, and core antibody may substitute for PCR).
- Current uncontrolled bacterial, viral or fungal infection (currently taking medication and progression of clinical symptoms).
- Autologous transplant < 12 months prior to enrollment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Two-year Event Free Survival (EFS)
Time frame: 2 years post-HCT
Event-free survival is defined as the time from HCT to relapse, death, initiation of post-HCT therapy to treat AML relapse, loss to follow up or end of study whichever comes first.
8 secondary outcomes
Two-year overall survival (OS)
Time frame: 2 years post-HCT
Disease relapse at 2 years
Time frame: 2 years post-HCT
Occurrence of acute grade II-IV and grade III-IV GVHD by 200 days post-HCT
Time frame: 200 days post-HCT
Occurrence of chronic GVHD at 2 years post-HCT
Time frame: 2 years post-HCT
Time to neutrophil engraftment
Time frame: 42 days post-HCT
Time to platelet engraftment
Time frame: 42 days post-HCT
Veno-occlusive Disease
Time frame: 2 years post-HCT
Chimerism
Time frame: 100 days post-HCT
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 7 Sep 2017.
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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.
David A. Jacobsohn, MD, ScM principal investigator
Children's National Research Institute
38 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Myeloid Leukemia, run by Center for International Blood and Marrow Transplant Research at 38 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 35 inclusion and 6 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 7 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 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.
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?
Two-year Event Free Survival (EFS) (time frame: 2 years post-HCT). 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 7 Sep 2017.