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

NCT02626715 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: STUDY19030327
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Myeloid Leukemia (AML); Myelodysplastic Syndrome (MDS); Hematopoietic Stem Cell Transplant (HSCT)

Outcome Measures

Primary Outcomes (3)

• Number of Non-relapsed Deaths by 100 Days Post-transplant in Pediatric Patients Receiving a Myeloablative or Reduced-intensity Preparative Regimen Prior to HSCT for High-risk AML and MDS.

  Number of non-relapsed deaths that occur

  Day 100

• Preliminary Efficacy (Event-free Survival at 6 Months) in Pediatric Patients Receiving a Myeloablative or Reduced-intensity Preparative Regimen Prior to HSCT for High-risk AML and MDS.

  Event-free survival at 6 months, where events are defined as relapse or death

  6 months

• Number of Non-relapsed Deaths by 6 Months Post-transplant in Pediatric Patients Receiving a Myeloablative or Reduced-intensity Preparative Regimen Prior to HSCT for High-risk AML and MDS.

  Number of non-relapsed deaths that occur

  Day 180

Secondary Outcomes (11)

• The Pace of Neutrophil Recovery

  Day of transplant to end of study (Day 365)

• The Pace of Platelet Recovery

  Day of transplant to end of study (Day 365)

• Number of Participants Developing Acute Graft Versus Host Disease (aGVHD) by Grade

  Day of transplant to end of study (Day 365)

• Number of Participants Developing Chronic Graft Versus Host Disease (cGVHD) by Grade

  Day of transplant to end of study (Day 365)

• Disease-free Survival (DFS)

  Day 100 and 180 post-transplant

Study Arms (2)

Reduced-Intensity Conditioning

ACTIVE COMPARATOR

Campath (alemtuzumab), Droxia (hydroxyurea), Fludara (fludarabine), Alkeran (melphalan), Thiotepa (triethylenethiophosphoramide) Trade Name (generic name)

Drug: Reduced-Intensity Conditioning Regimen

Myeloablative Conditioning

ACTIVE COMPARATOR

Campath (alemtuzumab), Thiotepa (triethylenethiophosphoramide) , Fludara (fludarabine), Busulfex (busulfan) Trade Name (generic name)

Drug: Myeloablative Conditioning Regimen

Interventions

Reduced-Intensity Conditioning Regimen DRUG

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

Also known as: Campath, Droxia, Fludara, Alkeran, Thiotepa

Reduced-Intensity Conditioning

Myeloablative Conditioning Regimen DRUG

Campath (alemtuzumab) - drug class: monoclonal antibody Thiotepa (triethylenethiophosphoramide) - drug class: cytotoxic agent Fludara (fludarabine) - drug class: antimetabolite Busulfex (busulfan) - drug class: alkylating agent

Also known as: Campath, Thiotepa, Fludara, Busulfex

Myeloablative Conditioning

Eligibility Criteria

• Age: 0 Months - 26 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Individuals must meet all the following criteria to be eligible for this study.
• Subject, parent, or legal guardian, if applicable, must have given written informed consent. For patients ≤ 17 years of age who are developmentally able, assent or affirmation will be obtained.
• Age 0-26, inclusive, at time of consent.
• Diagnosis of myelodysplastic syndrome or acute myeloid leukemia, either high-risk (defined below), relapsed or primary refractory, 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: RAM phenotype; adverse cytogenetic abnormalities of monosomy 5, monosomy 7, 5q deletion, or other unfavorable prognostic markers according to cytogenetics, FISH, or next generation sequencing (NGS); presence of FLT3 positive internal tandem duplication (FLT3/ITD+), particularly high allelic ratio; treatment-related AML; or positive minimal residual disease (MRD) at end of Induction I.
• Stem cell sources include bone marrow, peripheral blood stem cells, or umbilical cord blood. Related bone marrow, peripheral blood stem cell, or cord blood unit: sibling should be 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 DR-B1.
• Minimum pre-freezing cell dose for cord blood units: 3 x 10\^7 total nucleated cells/kg and 1.5 x 10\^5 CD34+ cells/kg. If this is not attainable, then double cord blood transplant should be considered.
• Subject must have adequate performance status: Lansky score ≥60% for patients \<16 years, Karnofsky score ≥60% for patients ≥16 years.
• Subject must have adequate pre-transplant organ function to undergo one of the two conditioning regimens, either the myeloablative conditioning (MAC) OR reduced-intensity conditioning (RIC) regimen. If a subject does not meet the following organ function criteria for the MAC regimen, the RIC regimen will be considered if eligibility criteria is met. The RIC regimen may also be considered, regardless of MAC eligibility, if deemed appropriate by the Principal Investigator and/or treating physician.
• Pre-transplant organ function criteria for Myeloablative Conditioning regimen:
• Renal: creatinine clearance or radioisotope GFR ≥70 mL/min/1.73 m2.
• Hepatic: total bilirubin ≤2.0 mg/dL unless the increase in bilirubin is attributable to Gilbert's syndrome; and SGOT (AST), SGPT (ALT), and Alkaline Phosphatase \<4 x upper limit of normal (ULN) for age.
• Cardiac: normal cardiac function by echocardiogram or radionuclide scan, as defined by left ventricular ejection fraction at rest \>45% or shortening fraction \>26%.
• Pulmonary: FEV1, FVC, and DLCO (corrected for hemoglobin) ≥50% of predicted; if unable to perform pulmonary function tests, then oxygen saturation ≥92% on room air.
• Pre-transplant organ function criteria for Reduced-Intensity Conditioning regimen:
• Renal: creatinine clearance or radioisotope GFR ≥70 mL/min/1.73 m2.

You may not qualify if:

• Individuals who meet any of the following criteria are not eligible for this protocol.
• Uncontrolled bacterial, viral, fungal, or other infection at the time of cytoreduction, defined by positive blood cultures and/or fevers \>38.0 within 24 hours of start of conditioning therapy.
• Females who are pregnant or who are lactating.
• Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.
• Recipient of either an autologous or allogeneic stem cell transplant within 3 months of the start of conditioning.
• Patients with any inherited bone marrow failure syndrome including, but not limited to, Fanconi anemia, Shwachman-Diamond syndrome, dyskeratosis congenita or Down syndrome (defined as either constitutional trisomy 21 or constitutional mosaicism of trisomy 21).

Sponsors & Collaborators

• Randy Windreich: lead

Study Sites (1)

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Related Publications (2)

• Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995 Jun;15(6):825-8.

  PMID: 7581076 BACKGROUND

• Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, Palmer J, Weisdorf D, Treister NS, Cheng GS, Kerr H, Stratton P, Duarte RF, McDonald GB, Inamoto Y, Vigorito A, Arai S, Datiles MB, Jacobsohn D, Heller T, Kitko CL, Mitchell SA, Martin PJ, Shulman H, Wu RS, Cutler CS, Vogelsang GB, Lee SJ, Pavletic SZ, Flowers ME. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015 Mar;21(3):389-401.e1. doi: 10.1016/j.bbmt.2014.12.001. Epub 2014 Dec 18.

  PMID: 25529383 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Alemtuzumab; Hydroxyurea; fludarabine phosphate; Melphalan; Thiotepa; Busulfan

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Urea; Amides; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Dr. Randy Windreich
• Organization: UPMC Children's Hospital of Pittsburgh

randy.windreich@chp.edu

412-692-5055

Study Officials

• Randy Windreich, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: September 24, 2015
• First Posted: December 10, 2015
• Study Start: September 4, 2015
• Primary Completion: April 12, 2023
• Study Completion: April 12, 2023
• Last Updated: July 16, 2024
• Results First Posted: July 16, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)