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CSL964_2001_MODULAATE Study (bei GvHD)

AcronymISRCTNEudraCTNCT (clinicaltrials.gov)DRKS
CSL964_20012018-000329-29NCT01700036

A Phase 2/3, Multicenter, randOmized, Double-blind, placebo-controlled, stUdy to evaLuate the safety and efficacy of Alpha-1 AntiTrypsin for the prEvention of graft-versushost disease in patients receiving hematopoietic cell transplant (MODULAATE Study)

Status: Active

Purpose / Objectives

Primary Outcome

  • To evaluate the efficacy of AAT at the selected dose for the prevention of acute GVHD following HCT.

Secondary Outcomes

  • To evaluate the efficacy of AAT for the prevention of post-HCT complications.
  • To evaluate the safety of AAT based on incidence of systemic infections and study drug related AEs.
  • To evaluate the steady state PK of AAT in HCT recipients.

Diagnosis

Patient attributes

Age

18-99

Inclusion criteria

  • Male or female subjects, ≥12 years of age, undergoing HCT for hematological malignancies, including leukemia, lymphoma and multiple myeloma.
  • Planned myeloablative conditioning regimen
  • Subjects must have an unrelated donor, matched or mismatched ( ie, 7/8 or 6/8) for HLA-A, -B, and -C at intermediate (or higher) resolution, or -DRB1 at high resolution using DNA-based typing.
  • Cardiac function: Ejection fraction at rest ≥ 45.0% or shortening fraction of ≥ 27.0% by echocardiogram or radionuclide scan (multigated acquisition [MUGA]).
  • Estimated creatinine clearance greater than 50.0 mL/minute.
  • Pulmonary function: Diffusing capacity of the lung for carbon monoxide (DLCO) ≥ 50% (adjusted for hemoglobin) of the predicted normal value, and forced expiratory volume in one second (FEV1) or forced vital capacity (FVC) ≥ 50% of the predicted normal value.
  • Liver function: total bilirubin < 2x the upper limit of normal (unless elevated bilirubin is attributed to Gilbert's Syndrome) and alanine aminotransferase / aspartate aminotransferase < 3.0x the upper limit of normal.
  • Signed written informed consent obtained before undergoing any study-specific procedures.

Exclusion criteria

  • Prior autologous or allogeneic HCT.
  • T-cell depleted transplant or planned use of anti-T cell antibody therapy either ex vivo or in vivo (ie, ATG, alemtuzumab) during the study.
  • Planned umbilical cord blood transplant.
  • Karnofsky Performance Score < 70%.
  • Active central nervous system involvement by malignant cells.
  • Uncontrolled bacterial, viral or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment.
  • Seropositive for human immunodeficiency virus-1 or -2.
  • Seropositive for Human T-Lymphotropic Virus-I or –II.
  • Active Hepatitis B or C viral replication by polymerase chain reaction.
  • Subjects who have received previous genetically engineered chimeric antigen receptor T-cell therapy (eg, CTL019, tisagenlecleucel, axicabtagene ciloleucel) as these patients are lifelong B-cell deficient and could have increased risk of infection.
  • A history of New York Heart Association Class III or IV heart failure within the last year.
  • Sustained hemodynamic instability at time of screening.
  • Women who are pregnant (positive serum or urine βHCG) or breastfeeding.
  • Females of childbearing potential (FCBP) or men who have sexual contact with FCBP unwilling to use 2 effective forms of birth control or abstinence for 3 months after transplantation.
  • History of uncontrolled autoimmune disease or on active treatment.
  • Current or prior other malignancies not including current indication for stem cell transplantation, except resected non-melanoma or any carcinoma in situ > 2 years resected. Non in situ carcinoma treated with curative intent ≥ 5 years previously will be allowed.
  • Hypersensitivity to any components of the investigational product or the placebo.
  • Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits;pose a significant risk to the subject; or interfere with interpretation of study data.
  • Prior treatment with AAT within 30 days of the screening visit.
  • Receipt of an investigational product within 30 days of the screening visit.

Trial design

  • Phase II
  • Phase III
  • Multicenter
  • Prospective
  • Randomized
  • Two-arm
  • Cohort
  • Double-blind
  • Open Label
  • Placebo-controlled

Intervention

  • Investigational Products for the study are AAT for Part 1 and AAT or placebo for Part 2 (Cohort 4).
  • The AAT loading dose will be administered on Day -1. AAT will be administered every 3 to 4 days (ie, twice weekly) beginning at Day 1 through Day 28. Subjects will receive AAT once weekly on Days 35, 42, 49, and 56.

 

Documents (password protected)

Responsibilities in overall trial

CSL Behring

National Coordinating Investigator

PD Dr. Dr. med. Udo Holtick

Study Sites

Klinik I für Innere Medizin

Study office

  • Klinisches Studienzentrum der Klinik I für Innere Medizin Köln

Status

Active

Principal Investigator

PD Dr. Dr. med. Udo Holtick

Deputy of Principal Investigator

  • Prof. Dr. med. Dr. h. c. Christoph Scheid
  • PD Dr. med. Marco Herling

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