Rabbit Anti-thymocyte Globulin in the Treatment of Patients With Low to Intermediate-1 Risk Myelodysplastic Syndrome

NCT00542828 | Terminated Phase 2 Results

• 2 other identifiers: ThymoHEM012062007-002532-28
• Study Type: interventional
• Target: 16
• Locations: 4 countries
• Sites: 7

Brief Summary

This is a Phase II, single-arm, open-label, multinational, multicenter study of rATG in patients with low or intermediate-1 risk MDS who have either failed 1 prior treatment with growth factor(s), hypomethylating agents (5-azacitidine or decitabine), or the antiangiogenic agents lenalidomide or thalidomide, or who have never been treated for MDS (i.e., treatment-naïve patients).

Conditions

Myelodysplastic Syndrome (MDS)

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Achieved Hematologic Improvement (HI)

  This is a measure of HI in the erythroid, platelet, and neutrophil lineages. Note that HI was observed in the erythroid lineage only, which is defined as a participant who had a \>=1.5 g/dL increase in hemoglobin from baseline (pretreatment value must have been \<11 g/dL) and who had a relevant reduction of units of red blood cell (RBC) transfusions by an absolute number of \>=4 RBC transfusions over 8 weeks as compared with the pretreatment transfusion number in the previous 8 weeks. These criteria were taken from the 2006 International Working Group criteria.

  12 months

Secondary Outcomes (11)

• Number of Participants With Duration of HI

  36 months

• Number of Participants Who Achieved Disease Remission

  36 months

• Duration of Disease Remission

  36 months

• Number of Participants Who Achieved Transfusion Independence

  36 months

• Number of Participants With Duration of Transfusion Independence

  36 months

Study Arms (1)

Thymoglobulin

EXPERIMENTAL

Biological: Thymoglobulin®, Rabbit Anti-thymocyte Globulin (rATG)

Interventions

Thymoglobulin®, Rabbit Anti-thymocyte Globulin (rATG) BIOLOGICAL

All patients were to be treated with rATG 3.75 mg/kg/day administered by intravenous (IV) infusion over ≥6 hours for 5 consecutive days (cumulative dose: 18.75 mg/kg)

Also known as: Rabbbit Anti-human thymocyte immunoglobulin

Thymoglobulin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient provided signed written informed consent.
• Patient had pathologically confirmed low or intermediate-1 risk MDS at the time of MDS diagnosis and at the time of screening.
• Patient had received no more than 1 prior treatment for MDS.
• Patient exhibited at least 1 hematologic cytopenia (anemia, neutropenia, or thrombocytopenia) over a period of ≥1 week.
• Patient had documentation of any prior transfusion requirements.
• Patient had an Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1, or 2.
• Patient was ≥18 and ≤70 years of age at time of signing the informed consent document (ICD).
• Patient was able to adhere to study visit schedule and all other protocol requirements.
• Patient was willing to practice a medically approved method of birth control during participation in the study (at least 12 months after the last infusion of rATG) (fertile male and female patients).

You may not qualify if:

• Patient was pregnant or lactating.
• Patient has had prior treatment with any ATG.
• Patient has received any immunomodulatory or immunosuppressing agents (excluding steroids) \<12 weeks prior to the first infusion of rATG.
• Patient has had a prior hematopoietic stem cell transplantation and/or other organ transplant.
• Patient has had a prior allergic reaction to rabbit proteins or excipients.
• Patient had any of the following subtypes of MDS: refractory anemia with ringed sideroblasts (RARS); chronic myelomonocytic leukemia (CMML) if white blood counts \>13x10\^9/L; or other MDS/myeloproliferative diseases (MPD).
• Patient had MDS associated with a 5q chromosomal deletion unless the patient received prior lenalidomide treatment \<4 weeks prior to the first infusion of rATG.
• Patient had MDS presumed secondary to exposure to chemicals or treatment with radiotherapy or chemotherapy.
• Patient received any investigational agents within 4 weeks prior to the first infusion of rATG.
• Patient has any of the following abnormalities: serum creatinine \>1.5 x upper limit of normal (ULN); aspartate transaminase (AST) and alanine transaminase (ALT) \>2.5 x ULN; or serum total bilirubin \>1.5 x ULN, except for unconjugated hyperbilirubinemia related to the patient's MDS.
• Patient received any treatment with non-steroidal anti-inflammatory drugs (NSAIDs) within 14 days prior to the start of treatment.
• Patient was known to be human immunodeficiency virus (HIV) positive.
• Patient had any prior diagnosis of malignancy other than MDS, unless the patient had been disease-free for at least 5 years following the completion of curative intent therapy.
• Patient had any serious medical condition (other than MDS) that would limit survival to \<2 years.
• Patient had active acute or chronic infection, including cytomegaloviremia (CMV) infection or deep tissue infection.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (7)

Hopital Avicenne/University

Paris, 93009, France

Location

St. Johannes-Hospital Duisburg

Duisburg, 47166, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

UMC St Radboud Centraal

Nijmegen, 6525 GA, Netherlands

Location

Royal Bournemouth Hospital

Bournemouth, England, BH7 7DW, United Kingdom

Location

St. James Hospital

Leeds, England, LS9 7TF, United Kingdom

Location

King's College Hospital

London, England, SE5 9RS, United Kingdom

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

thymoglobulin; Antilymphocyte Serum

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Limitations and Caveats

The study was terminated early due to a slow enrollment rate; therefore, only safety data were collected from participants for 45 days following the last day of infusion (Day 5).

Results Point of Contact

• Title: Genzyme MedInfo
• Organization: Genzyme Corporation

medinfo@genzyme.com

800-745-4447

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2007
• First Posted: October 12, 2007
• Study Start: October 1, 2007
• Primary Completion: May 1, 2009
• Study Completion: July 1, 2009
• Last Updated: April 3, 2015
• Results First Posted: April 27, 2010

Record last verified: 2015-03

Locations

DE (2); FR (1); GB (3); NL (1)