Acute Myeloid Leukemia Clinical Trial
Official title:
The Role of Minimal Residual Disease Testing Before and After Hematopoietic Cell Transplantation for Pediatric Acute Myeloid Leukemia
Verified date | September 2017 |
Source | Center for International Blood and Marrow Transplant Research |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Observational |
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.
Status | Completed |
Enrollment | 150 |
Est. completion date | May 2017 |
Est. primary completion date | May 2017 |
Accepts healthy volunteers | No |
Gender | All |
Age group | N/A to 21 Years |
Eligibility |
Inclusion Criteria: 1. Subject or legal guardian to understand and voluntarily sign an informed consent. 2. Age 0-21 at time of transplant. 3. Karnofsky score = 70% (age = 16 years old), or Lansky score = 70% (age<16 years old). 4. 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 - 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. 5. 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 6. 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. 7. 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 Exclusion Criteria: 1. Women who are pregnant (positive HCG) or breastfeeding. 2. Evidence of HIV infection or HIV positive serology. 3. Positive viral load (PCR) for Hepatitis B or C (negative serology, surface antigen, and core antibody may substitute for PCR). 4. Current uncontrolled bacterial, viral or fungal infection (currently taking medication and progression of clinical symptoms). 5. Autologous transplant < 12 months prior to enrollment. 6. Prior allogeneic hematopoietic stem cell transplant. |
Country | Name | City | State |
---|---|---|---|
Canada | Alberta Children's Hospital | Calgary | Alberta |
Canada | Hopital Ste. Justine | Montreal | Quebec |
Canada | The Montreal Children's Hospital | Montreal | Quebec |
Canada | Children's & Women's Health Centre of British Columbia | Vancouver | British Columbia |
United States | University of Michigan | Ann Arbor | Michigan |
United States | Children's Healthcare of Atlanta | Atlanta | Georgia |
United States | The Children's Hospital Colorado | Aurora | Colorado |
United States | Johns Hopkins | Baltimore | Maryland |
United States | The Children's Hospital of Alabama, University of Alabama at Birmingham | Birmingham | Alabama |
United States | Dana Farber Cancer Institute | Boston | Massachusetts |
United States | Roswell Park Cancer Institute | Buffalo | New York |
United States | University of North Carolina at Chapel Hill | Chapel Hill | North Carolina |
United States | Medical University of South Carolina | Charleston | South Carolina |
United States | Lurie Children's Hospital of Chicago | Chicago | Illinois |
United States | Cleveland Clinic | Cleveland | Ohio |
United States | University Hospitals of Cleveland Case Medical Ctr | Cleveland | Ohio |
United States | Children's Hospital of Michigan | Detroit | Michigan |
United States | Duke University Medical Center | Durham | North Carolina |
United States | Hackensack University Medical Center | Hackensack | New Jersey |
United States | Penn State Milton S. Hershey Medical Center | Hershey | Pennsylvania |
United States | Riley Hospital for Children/Indiana University | Indianapolis | Indiana |
United States | University of Mississippi Medical Center | Jackson | Mississippi |
United States | Loma Linda University | Loma Linda | California |
United States | University of Louisville | Louisville | Kentucky |
United States | Miami Children's Hospital | Miami | Florida |
United States | Children's Hospital of Wisconsin | Milwaukee | Wisconsin |
United States | Columbia University - The Morgan Stanley Children's Hospital of New York | New York | New York |
United States | Mount Sinai School of Medicine | New York | New York |
United States | Phoenix Children's Hospital | Phoenix | Arizona |
United States | Oregon Health & Sciences University - Doerbecher Children's | Portland | Oregon |
United States | Virginia Commonwealth University | Richmond | Virginia |
United States | Washington University, St. Louis Children's Hospital | Saint Louis | Missouri |
United States | All Children's Hospital | Saint Petersburg | Florida |
United States | University of Utah - Primary Children's Medical Center | Salt Lake City | Utah |
United States | Methodist Children's Hospital of South Texas/Texas Institute of Medicine and Surgery | San Antonio | Texas |
United States | University of California San Francisco | San Francisco | California |
United States | New York Medical College | Valhalla | New York |
United States | Children's National Medical Center | Washington, D.C. | District of Columbia |
Lead Sponsor | Collaborator |
---|---|
Center for International Blood and Marrow Transplant Research | Otsuka Pharmaceutical Development & Commercialization, Inc., Pediatric Blood and Marrow Transplant Consortium, St. Baldrick's Foundation |
United States, Canada,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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. | 2 years post-HCT | |
Secondary | 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. | 2 years post-HCT | |
Secondary | 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. | 2 years post-HCT | |
Secondary | 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. | 200 days post-HCT | |
Secondary | 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. | 2 years post-HCT | |
Secondary | 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. | 42 days post-HCT | |
Secondary | 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. | 42 days post-HCT | |
Secondary | 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. | 2 years post-HCT | |
Secondary | Chimerism | Whole blood chimerism and T-cell chimerism will be classified according to full (>95%), mixed (5-95%), or none (<5%) at 100 days. | 100 days post-HCT |
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