Acute Myeloid Leukemia Clinical Trial

MRD Testing Before and After Hematopoietic Cell Transplantation for Pediatric Acute Myeloid Leukemia

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. 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) 100 (+-20 days) HCT. For two years after transplant, subject's follow-up data will be collected using Research Level Forms in CIBMTR Net internet entry system. The main objective is determine whether there any association between level of pre-transplant post-transplant bone marrow MRD WT1 flow cytometry with 2-year event-free-survival, estimate strength that terms predictive accuracy MRD. investigators hypothesize measurable at either time point associated decreased event-free survival.

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Full 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.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

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
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

Exclusion Criteria:

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.

Study is for people with:

Acute Myeloid Leukemia

Estimated Enrollment:

150

Study ID:

NCT01385787

Recruitment Status:

Completed

Sponsor:

Center for International Blood and Marrow Transplant Research

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There are 38 Locations for this study

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The Children's Hospital of Alabama, University of Alabama at Birmingham
Birmingham Alabama, 35233, United States
Phoenix Children's Hospital
Phoenix Arizona, 85016, United States
Loma Linda University
Loma Linda California, 92354, United States
University of California San Francisco
San Francisco California, 94143, United States
The Children's Hospital Colorado
Aurora Colorado, 80045, United States
Children's National Medical Center
Washington, D.C. District of Columbia, 20910, United States
Miami Children's Hospital
Miami Florida, 33155, United States
All Children's Hospital
Saint Petersburg Florida, 33701, United States
Children's Healthcare of Atlanta
Atlanta Georgia, 30322, United States
Lurie Children's Hospital of Chicago
Chicago Illinois, 60611, United States
Riley Hospital for Children/Indiana University
Indianapolis Indiana, 46202, United States
University of Louisville
Louisville Kentucky, 40202, United States
Johns Hopkins
Baltimore Maryland, 21287, United States
Dana Farber Cancer Institute
Boston Massachusetts, 02215, United States
University of Michigan
Ann Arbor Michigan, 48109, United States
Children's Hospital of Michigan
Detroit Michigan, 48201, United States
University of Mississippi Medical Center
Jackson Mississippi, 39216, United States
Washington University, St. Louis Children's Hospital
Saint Louis Missouri, 63110, United States
Hackensack University Medical Center
Hackensack New Jersey, 07601, United States
Roswell Park Cancer Institute
Buffalo New York, 14263, United States
Mount Sinai School of Medicine
New York New York, 10029, United States
Columbia University - The Morgan Stanley Children's Hospital of New York
New York New York, 10032, United States
New York Medical College
Valhalla New York, 10595, United States
University of North Carolina at Chapel Hill
Chapel Hill North Carolina, 27599, United States
Duke University Medical Center
Durham North Carolina, 27705, United States
University Hospitals of Cleveland Case Medical Ctr
Cleveland Ohio, 44106, United States
Cleveland Clinic
Cleveland Ohio, 44195, United States
Oregon Health & Sciences University - Doerbecher Children's
Portland Oregon, 97239, United States
Penn State Milton S. Hershey Medical Center
Hershey Pennsylvania, 17033, United States
Medical University of South Carolina
Charleston South Carolina, 29425, United States
Methodist Children's Hospital of South Texas/Texas Institute of Medicine and Surgery
San Antonio Texas, 78229, United States
University of Utah - Primary Children's Medical Center
Salt Lake City Utah, 84108, United States
Virginia Commonwealth University
Richmond Virginia, 23219, United States
Children's Hospital of Wisconsin
Milwaukee Wisconsin, 53226, United States
Alberta Children's Hospital
Calgary Alberta, T3B 6, Canada
Children's & Women's Health Centre of British Columbia
Vancouver British Columbia, V6T 1, Canada
The Montreal Children's Hospital
Montreal Quebec, H3H 1, Canada
Hopital Ste. Justine
Montreal Quebec, H3T 1, Canada

How clear is this clinincal trial information?

Study is for people with:

Acute Myeloid Leukemia

Estimated Enrollment:

150

Study ID:

NCT01385787

Recruitment Status:

Completed

Sponsor:


Center for International Blood and Marrow Transplant Research

How clear is this clinincal trial information?

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