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Reduced-Intensity Conditioning (RIC) and Myeloablative Conditioning (MAC) for HSCT in AML/MDS

This study is currently recruiting participants.
Verified April 2017 by Randy Windreich, University of Pittsburgh
Sponsor:
ClinicalTrials.gov Identifier:
NCT02626715
First Posted: December 10, 2015
Last Update Posted: April 7, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Randy Windreich, University of Pittsburgh
September 24, 2015
December 10, 2015
April 7, 2017
September 4, 2015
September 2018   (Final data collection date for primary outcome measure)
  • Safety (non-relapse mortality at Day 100) in pediatric patients receiving a myeloablative or reduced-intensity preparative regimen prior to HSCT for high-risk AML and MDS. [ Time Frame: Day 100 ]
  • Preliminary efficacy (disease-free survival at 1 year) in pediatric patients receiving a myeloablative or reduced-intensity preparative regimen prior to HSCT for high-risk AML and MDS. [ Time Frame: 1 year ]
Same as current
Complete list of historical versions of study NCT02626715 on ClinicalTrials.gov Archive Site
  • The pace of neutrophil and platelet recovery using absolute neutrophil count and platelet count, respectively. [ Time Frame: 180 days ]
  • The incidence of acute Graft versus Host Disease (GVHD) (II-IV, III-IV) and chronic GVHD. [ Time Frame: 2 years ]
  • The number of subjects with disease-free survival (DFS) by Day 100 and 180 post-transplant, using adverse events assessed by CTCAE version 4.0. [ Time Frame: Day 100 and 180 ]
  • The number of subjects with treatment-related mortality (TRM) by Day 100 and 180 post-transplant, using adverse events assessed by CTCAE version 4.0. [ Time Frame: Day 100 and 180 ]
  • The number of subjects with overall survival (OS) by Day 100 and 180 post-transplant, using adverse events assessed by CTCAE version 4.0. [ Time Frame: Day 100 and 180 ]
  • The pace of immune reconstitution using lymphocyte subset panel and chimerism assay (recipient's percentage of donor and recipient stem cell populations) [ Time Frame: 180 days ]
  • Day 0 Campath (Alemtuzumab) level [ Time Frame: Baseline ]
  • Correlation of Day 0 Campath (alemtuzumab) levels with rate of relapse, rate of viral infections, and pace of immune reconstitution. [ Time Frame: 180 days ]
  • Incidence of primary graft failure. [ Time Frame: 1 year ]
  • Incidence of Grades 4 and 5 adverse events as assessed by CTCAE 4.0. [ Time Frame: 1 year ]
  • The pace of neutrophil and platelet recovery using absolute neutrophil count and platelet count, respectively. [ Time Frame: 180 days ]
  • The incidence of acute Graft versus Host Disease (GVHD) (II-IV, III-IV) and chronic GVHD. [ Time Frame: 2 years ]
  • The number of subjects with disease-free survival (DFS) by Day 100 and 180 post-transplant, using adverse events assessed by CTCAE version 4.0. [ Time Frame: 180 days ]
  • The number of subjects with treatment-related mortality (TRM) by Day 100 and 180 post-transplant, using adverse events assessed by CTCAE version 4.0. [ Time Frame: 180 days ]
  • The number of subjects with overall survival (OS) by Day 100 and 180 post-transplant, using adverse events assessed by CTCAE version 4.0. [ Time Frame: 180 days ]
  • The pace of immune reconstitution using lymphocyte subset panel and chimerism assay (recipient's percentage of donor and recipient stem cell populations) [ Time Frame: 180 days ]
  • Day 0 Campath (Alemtuzumab) level [ Time Frame: Baseline ]
  • Correlation of Day 0 Campath (alemtuzumab) levels with rate of relapse, rate of viral infections, and pace of immune reconstitution. [ Time Frame: 180 days ]
  • Incidence of primary graft failure. [ Time Frame: 1 year ]
  • Incidence of Grades 4 and 5 adverse events as assessed by CTCAE 4.0. [ Time Frame: 1 year ]
Not Provided
Not Provided
 
Reduced-Intensity Conditioning (RIC) and Myeloablative Conditioning (MAC) for HSCT in AML/MDS
A Phase II Study of Myeloablative and Reduced-Intensity Conditioning Regimens for Children With Acute Myeloid Leukemia or Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
The purpose of this study is to compare safety and efficacy of reduced-intensity conditioning and myeloablative conditioning regimens prior to HSCT in high-risk AML/MDS pediatric and young adult patients. This study investigates the use of two novel conditioning therapies for hematopoietic stem cell transplant (HSCT). The primary focus of both the investigators' myeloablative and reduced-intensity conditioning regimens is to reduce overall toxicity so that pediatric and young adult patients with high-risk AML/MDS with significant pretransplant comorbidities who would have been ineligible to proceed to HSCT previously can now receive potentially life-saving treatment.
Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Acute Myeloid Leukemia (AML)
  • Myelodysplastic Syndrome (MDS)
  • Hematopoietic Stem Cell Transplant (HSCT)
  • Drug: Reduced-Intensity Conditioning Regimen
    Campath (alemtuzumab) - drug class: monoclonal antibody Droxia (hydroxyurea) - drug class: antimetabolite Fludara (fludarabine) - drug class: antimetabolite Alkeran (melphalan) - drug class: alkylating agent Thiotepa (triethylenethiophosphoramide) - drug class: cytotoxic agent
    Other Name: Campath, Droxia, Fludara, Alkeran, Thiotepa
  • Drug: Myeloablative Conditioning Regimen
    Campath (alemtuzumab) - drug class: monoclonal antibody Thiotepa (triethylenethiophosphoramide) - drug class: cytotoxic agent Fludara (fludarabine) - drug class: antimetabolite Busulfex (busulfan) - drug class: alkylating agent
    Other Name: Campath, Thiotepa, Fludara, Busulfex
  • Active Comparator: Reduced-Intensity Conditioning

    Campath (alemtuzumab), Droxia (hydroxyurea), Fludara (fludarabine), Alkeran (melphalan), Thiotepa (triethylenethiophosphoramide)

    Trade Name (generic name)

    Intervention: Drug: Reduced-Intensity Conditioning Regimen
  • Active Comparator: Myeloablative Conditioning

    Campath (alemtuzumab), Thiotepa (triethylenethiophosphoramide) , Fludara (fludarabine), Busulfex (busulfan)

    Trade Name (generic name)

    Intervention: Drug: Myeloablative Conditioning Regimen
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
16
September 2019
September 2018   (Final data collection date for primary outcome measure)

Inclusion Criteria:

Eligibility Criteria for Myeloablative Conditioning Transplant

  1. Patient must be between 1 month to 22 years of age.
  2. Diagnosis of acute myeloid leukemia or myelodysplastic syndrome, either high-risk, relapsed or primary refractory, minimal residual disease (MRD)-positive without circulating myeloblasts or active extramedullary disease at the time of transplant. Active marrow disease is permitted. ("High-risk" AML features are defined by the following: greater than 15% blasts in the bone marrow after the first course of Induction chemotherapy; adverse cytogenetic abnormalities of monosomy 5, monosomy 7, or 5q deletion; presence of FLT3 positive internal tandem duplication (FLT3/ITD+), particularly high allelic ratio; or treatment-related AML.)
  3. Stem cell sources include bone marrow, peripheral blood stem cells, or umbilical cord blood.
  4. Related bone marrow, peripheral blood stem cell, or cord blood unit: Sibling should be human leukocyte antigen (HLA)-matched at A, B, and DR-B1 loci. Unrelated cord blood unit should be at a minimum of 4/6 matched at antigen level on HLA A and B, and allele level at HLA DR-B1 loci.

    Unrelated bone marrow or peripheral blood stem cell donor should be HLA allele level matched at A, B, C, and DR-B1.

  5. Minimum prefreezing cell dose for cord blood units: 3 x 10^7 total nucleated cells/kg and 1.5 x 10^5 CD34+ cells/kg (cluster of differentiation 34). If this is not attainable, then double cord blood transplant should be considered.
  6. Patient, parent, or legal guardian must have given written informed consent and/or assent.
  7. Patient must have adequate performance status (Lansky score ≥60% for patients <16 years; Karnofsky score ≥60% for patients ≥16 years).
  8. Patient must have adequate pre-transplant organ function as defined by:

8a. Renal: Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥70 mL/min/1.73 m2.

8b. Hepatic: Total bilirubin ≤2.0 mg/dL unless the increase in bilirubin is attributable to Gilbert's syndrome; and SGOT (AST) (serum glutamate oxaloacetate transaminase), SGPT (ALT) (serum glutamate pyruvate transaminase), and Alkaline Phosphatase <4 x upper limit of normal (ULN) for age.

8c. Cardiac: Normal cardiac function by echocardiogram or radionuclide scan, as defined by left ventricular ejection fraction at rest >45%, or shortening fraction >26%.

8d. Pulmonary: FEV1 (forced expiratory volume at one second), FVC (forced vital capacity), and DLCO (diffusing capacity of lung for carbon monoxide) (corrected for hemoglobin) ≥50% of predicted; if unable to perform pulmonary function tests, then oxygen saturation ≥92% on room air.

Eligibility Criteria for Reduced-Intensity Conditioning Transplant

  1. Patient must be between 0 -22 years of age.
  2. Patient must meet criteria 5.1.2-5.1.7 of eligibility criteria.
  3. Patient is excluded from myeloablative conditioning transplant due to failure to meet any of the criteria outlined in 5.1.8.
  4. Patient must have adequate pre-transplant organ function as defined by:

4a. Renal: Creatinine clearance or radioisotope GFR ≥70 mL/min/1.73 m2. 4b. Hepatic: Total bilirubin ≤2.5 mg/dL unless the increase in bilirubin is attributable to Gilbert's syndrome; and SGOT (AST), SGPT (ALT), and Alkaline Phosphatase <5 x upper limit of normal (ULN) for age.

4c. Cardiac: Normal cardiac function by echocardiogram or radionuclide scan, as defined by left ventricular ejection fraction at rest >40%, or shortening fraction >26%.

4d. Pulmonary: FEV1, FVC, and DLCO (corrected for hemoglobin) ≥40% of predicted; if unable to perform pulmonary function tests, then oxygen saturation ≥92% on room air.

Exclusion Criteria:

Exclusion Criteria for Myeloablative Conditioning Transplant

  1. Recipient of an autologous stem cell transplant.
  2. Allogeneic hematopoietic stem cell transplant within the previous 3 months.
  3. Uncontrolled bacterial, viral, fungal, or other infection at the time of cytoreduction. Uncontrolled infection defined by positive blood cultures and fevers >38.0 within 24-48 hours of start of conditioning therapy.
  4. Evidence of HIV/HTLV (human T-lymphotropic virus) infection or HIV/HTLV positive serology.
  5. Pregnancy or lactating. All females of 11 years of age or older and/or who have begun menstruating will be screened for HCG (human chorionic gonadotropin) by either urinalysis or a blood sample in order to screen for pregnancy status.
  6. Patients with any inherited bone marrow failure syndrome (including, but not limited to, Fanconi anemia, Shwachman-Diamond syndrome, and dyskeratosis congenital) or Down syndrome (defined as either constitutional trisomy 21 or constitutional mosaicism of trisomy 21).
Sexes Eligible for Study: All
1 Month to 22 Years   (Child, Adult)
No
Contact: Randy Windreich, MD 412-692-5055
United States
 
 
NCT02626715
PRO14100126
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Plan to Share IPD: No
Randy Windreich, University of Pittsburgh
University of Pittsburgh
Not Provided
Principal Investigator: Randy Windreich, MD Children's Hospital of Pittsburgh of UPMC
University of Pittsburgh
April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP