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

This study has been terminated.
(Study terminated due to slow enrollment.)
Sponsor:
Information provided by (Responsible Party):
Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT00542828
First received: October 10, 2007
Last updated: August 13, 2012
Last verified: August 2012
  Purpose

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).


Condition Intervention Phase
Myelodysplastic Syndrome (MDS)
Biological: Thymoglobulin®, Rabbit Anti-thymocyte Globulin (rATG)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of the Efficacy of Rabbit Anti-thymocyte Globulin (rATG) in Patients With Low and Intermediate-1 Risk Myelodysplastic Syndrome

Resource links provided by NLM:


Further study details as provided by Genzyme, a Sanofi Company:

Primary Outcome Measures:
  • Number of Participants Who Achieved Hematologic Improvement (HI) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Participants With Duration of HI [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    This is a measure of the duration of HI for those participants who achieved HI. Duration of HI is defined as the time from confirmation of HI response to the date of first documentation of HI relapse or death due to any cause, whichever occurs first.

  • Number of Participants Who Achieved Disease Remission [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    Disease remission is defined as a participant whose best response to therapy was a complete remission or partial remission. A complete remission is defined as: bone marrow <=5% myeloblasts with normal maturation of all cell lines; persistent dysplasia noted; and peripheral blood hemoglobin >=11 g/dL, platelets >=100 x 10^9/L, neutrophils >=1.0 x 10^9/L, and blasts 0%. Partial remission is defined as: all complete remission criteria if abnormal before treatment, except bone marrow blasts decreased by >=50% over pretreatment, but still >5%; and cellularity and morphology not relevant.

  • Duration of Disease Remission [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    This is a measure of the duration of overall disease remission only for those participants who achieved an overall remission. Duration of overall remission is defined as the time from first documentation of overall remission to the date of first documentation of disease relapse or death due to any cause, whichever occurs first.

  • Number of Participants Who Achieved Transfusion Independence [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    This is a measure of transfusion independence, which is defined as a participant with no transfusions for a period of 8 consecutive calendar weeks after first dose. Transfusion independence was to be calculated only for those participants who had documented transfusions during the 8 weeks prior to enrollment.

  • Number of Participants With Duration of Transfusion Independence [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    This is a measure of the duration of transfusion independence only for those participants who achieved transfusion independence. Duration of transfusion independence is defined as the longest period of time during which a participant requires no transfusions.

  • Number of Participants With a Relapse Following HI [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    This is a measure of relapse following HI, which is defined as a participant who experiences at least one of the following: >=50% decrease from maximum response levels in granulocytes or platelets; >=1.5 g/dL reduction in hemoglobin; or transfusion dependence.

  • Number of Participants With a Relapse Following Overall Remission [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    This is a measure of relapse following an overall remission only for participants who experienced either a complete or partial remission. Relapse following an overall remission is defined as a participant who meets any of the following criteria: a return to pretreatment bone marrow blast percentage; decrease of >=50% from maximum remission levels in neutrophils or platelets; reduction in hemoglobin concentration by >=1.5 g/dL from maximum remission levels; or transfusion dependence.

  • Number of Participants With Progression-free Survival [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    This is a measure of a progression-free survival which is defined as the time from the participant's first dose to the date of disease progression, lost to follow-up or death due to any cause, whichever occurs first.

  • Number of Participants With Transformation to Acute Myeloid Leukemia [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    This is a measure of transformation to acute myeloid leukemia only for participants who have bone marrow assessments. Transformation to acute myeloid leukemia is defined as the earliest date a participant experiences bone marrow blasts of >=20% after the start of treatment.

  • Number of Participants With a Cytogenetic Response [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    This is a measure of cytogenic response for participants whose best response to therapy is a either a complete or partial cytogenetic response. A complete cytogenetic response is defined as the disappearance of the chromosomal abnormality without appearance of new ones. A partial cytogenetic response is defined as at least 50% reduction of the chromosomal abnormality.

  • Number of Participants With a Marrow Remission [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    This is a measure of bone marrow complete remission for participants who experience a remission. Bone marrow complete remission is defined as a bone marrow assessment of <=5% myeloblasts and decrease by >=50% over pretreatment.


Enrollment: 16
Study Start Date: October 2007
Study Completion Date: July 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Thymoglobulin Biological: Thymoglobulin®, Rabbit Anti-thymocyte Globulin (rATG)
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)
Other Name: Rabbbit Anti-human thymocyte immunoglobulin

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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).

Exclusion Criteria:

  • 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.
  • Patient had any other serious medical condition, uncontrolled illness (including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia), social condition, or psychiatric illness that would prevent the patient from signing the informed consent document (ICD), or would place the patient at unacceptable risk if he/she participated in the study, or that would limit compliance with study requirements.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00542828

Locations
France
Hopital Avicenne/University
Paris, France, 93009
Germany
St. Johannes-Hospital Duisburg
Duisburg, Germany, 47166
Medizinische Hochschule Hannover
Hannover, Germany, 30625
Netherlands
UMC St Radboud Centraal
Nijmegen, Netherlands, 6525 GA
United Kingdom
Royal Bournemouth Hospital
Bournemouth, England, United Kingdom, BH7 7DW
St. James Hospital
Leeds, England, United Kingdom, LS9 7TF
King's College Hospital
London, England, United Kingdom, SE5 9RS
Sponsors and Collaborators
Genzyme, a Sanofi Company
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

No publications provided

Responsible Party: Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier: NCT00542828     History of Changes
Other Study ID Numbers: ThymoHEM01206, 2007-002532-28
Study First Received: October 10, 2007
Results First Received: April 7, 2010
Last Updated: August 13, 2012
Health Authority: United States: Food and Drug Administration
Germany: Paul-Ehrlich-Institut
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
European Union: European Medicines Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Neoplasms
Pathologic Processes
Precancerous Conditions
Antilymphocyte Serum
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014