- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02333838
Reduced Toxicity Conditioning Prior to Unrelated Cord Cell Transplantation for High Risk Myeloid Malignancies (TBF-Cord)
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Vandoeuvre les Nancy, France, 54511
- Hôpital de Brabois, Hématologie Clinique et thérapie cellulaire
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age ≥18 years and ≤ 65 years
- Patients diagnosed with one of the following diseases (validation of the indication of allogeneic
HSCT with an alternative source of hematopoietic stem cells by centers' local RCP):
- Acute myelogenous leukemia (AML) with intermediate or high risk features ((≥ intermediate risk 1) in CR1 or above according to centers' decision
- Myelodysplastic syndromes with International Prognostic Scoring System (IPSS) score ³ 2 (cf. appendix 3) or with symptomatic pancytopenia according to centers' decision
- Chronic myelomonocytic leukemia (CMML)
- Both MDS and CMML should have ≤ 10% blasts at transplantation
- Absence of a matched sibling or unrelated donor (10/10 or 9/10 if mismatch on HLA Cw, based on each center's donor selection criteria)
- Cord blood units must be matched with patient at 4, 5, or 6/6 HLA loci, (class I antigenic & class II allelic level)with a minimum of 3.5 x 10^7 TNC/kg recipient body weight in the pre-thawed fraction and with ≥2.5x10^7 TNC/kg for the richest cord blood unit and ≥ 1.5x10^7 TNC/kg for the poorest blood unit in case of 2 cord blood units
- Performance status : OMS score ≤ 1 (cf. appendix 5)
- Cardiac function - left ventricular ejection fraction ≥ 45%.
- Pulmonary function - diffusion capacity of at least 50% predicted.
- Serum creatinine clearance 0 ml/min.
- SGPT 4x normal , serum bilirubin < 2 x normal.
- Written informed consent.
- Progestative treatment for women with persisting menstrual periods
Exclusion Criteria:
- Presence of a matched sibling or unrelated available donor (10/10 or 9/10 if mismatch on HLA Cw in centers performing 9/10 HLA mismatched transplants)
- Active infection at time of conditioning. In case of uncertainty regarding whether a previous infection is resolved or not, this will be discussed with the PI on a case by case basis.
- Pregnancy in women with child bearing potential (pregnancy test performed within 2-4 weeks of study entry).
- HIV positive
- Active CNS leukemia
- Chronic or active Hepatitis B or Hepatitis C. If questions about liver health discuss with PI and strongly consider liver biopsy.
- Poor performance status : OMS score > 1
- Life expectancy is severely limited by concomitant illness and expected to be <12 weeks.
- Left ventricular ejection fraction <45%. Uncontrolled arrhythmias or symptomatic cardiac disease.
- Symptomatic pulmonary disease. FEV1, FVC and DLCO <50% of expected corrected for hemoglobin.
- Serum creatinine clearance (Crockoft) below 50 mL/m per 1.73 m² or requiring dialysis
- Vaccination with alive vaccine (virus or bacteria) < 3 months
- Fludarabine contra-indication
- Thymoglobuline contra-indication
- Patient under guardianship or curatorship
Study Plan
How is the study designed?
Design Details
- Primary Purpose: OTHER
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Reduced toxicity conditioning regimen
Reduced toxicity conditioning regimen (thiotepa, busulfan, fludarabine and ATG) followed by unrelated cord blood allogeneic stem cell transplant for high risk myeloïd malignancies. The conditioning regimen will include:
In patient with co-morbidities and/or older than 60 years, conditioning could be reduced after consulting the coordinator of the study:
|
IV Thiotepa (5 mg/Kg/day for 2 days) (Day -7 and -6) or IV Thiotepa (5 mg/Kg/day for 2 days) (Day -6)
Other Names:
IV fludarabine (40 mg/m²/day for 4 days) (from Day-5 to day -2)
Other Names:
(Busilvex 130 mg/m2/day for 3 days) (Day-5, -4 and -3) or (Busilvex 100 mg/m2/day for 3 days) (Day-5, -4 and -3)
Other Names:
(Thymogobuline®, 2.5 mg/kg/day for 2 days) (Day-3 and -2)
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cumulative incidence of NRM at 12 months after transplantation
Time Frame: 12 months after transplantation
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Cumulative incidence of NRM at 12 months after transplantation : Safety and efficacy of the pre-transplant reduced toxicity conditioning regimen
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12 months after transplantation
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of engraftment after transplantation
Time Frame: 12 months after transplantation
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Incidence of neutrophil engraftment (day and proportion of patients reaching neutrophils >0.5x109/L); and platelets recovery (day and proportion of patients reaching platelets > 20 x 109 / L without transfusion) after transplantation
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12 months after transplantation
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Incidence and severity of acute GVHD
Time Frame: 6 months after transplantation
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Incidence and severity of acute GVHD (diagnosed and graded as standard criteria)
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6 months after transplantation
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Incidence and severity of chronic GVHD
Time Frame: 12 months after transplantation
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Incidence and severity of chronic GVHD (diagnosed and graded as standard criteria detailed )
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12 months after transplantation
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Rate of disease relapse at one year after transplantation
Time Frame: 12 months after transplantation
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Incidence of disease relapse at one year after transplantation (relapse is defined on the basis of morphologica evidence of leukemic cells in the bone marrow or other sites)
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12 months after transplantation
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Quality of life
Time Frame: 12 months after transplantation
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Evaluation of the quality of life (using a french translation of the FACT-BMT (version 4.0)
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12 months after transplantation
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Collaborators and Investigators
Investigators
- Principal Investigator: Marie Thérèse RUBIO, CHRU Nancy
Publications and helpful links
General Publications
- Rocha V, Labopin M, Sanz G, Arcese W, Schwerdtfeger R, Bosi A, Jacobsen N, Ruutu T, de Lima M, Finke J, Frassoni F, Gluckman E; Acute Leukemia Working Party of European Blood and Marrow Transplant Group; Eurocord-Netcord Registry. Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia. N Engl J Med. 2004 Nov 25;351(22):2276-85. doi: 10.1056/NEJMoa041469.
- Arcese W, Rocha V, Labopin M, Sanz G, Iori AP, de Lima M, Sirvent A, Busca A, Asano S, Ionescu I, Wernet P, Gluckman E; Eurocord-Netcord Transplant group. Unrelated cord blood transplants in adults with hematologic malignancies. Haematologica. 2006 Feb;91(2):223-30.
- Atsuta Y, Suzuki R, Nagamura-Inoue T, Taniguchi S, Takahashi S, Kai S, Sakamaki H, Kouzai Y, Kasai M, Fukuda T, Azuma H, Takanashi M, Okamoto S, Tsuchida M, Kawa K, Morishima Y, Kodera Y, Kato S; Japan Cord Blood Bank Network. Disease-specific analyses of unrelated cord blood transplantation compared with unrelated bone marrow transplantation in adult patients with acute leukemia. Blood. 2009 Feb 19;113(8):1631-8. doi: 10.1182/blood-2008-03-147041. Epub 2008 Dec 22.
- Eapen M, Rocha V, Sanz G, Scaradavou A, Zhang MJ, Arcese W, Sirvent A, Champlin RE, Chao N, Gee AP, Isola L, Laughlin MJ, Marks DI, Nabhan S, Ruggeri A, Soiffer R, Horowitz MM, Gluckman E, Wagner JE; Center for International Blood and Marrow Transplant Research; Acute Leukemia Working Party Eurocord (the European Group for Blood Marrow Transplantation); National Cord Blood Program of the New York Blood Center. Effect of graft source on unrelated donor haemopoietic stem-cell transplantation in adults with acute leukaemia: a retrospective analysis. Lancet Oncol. 2010 Jul;11(7):653-60. doi: 10.1016/S1470-2045(10)70127-3.
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Leukemia
- Neoplasms
- Leukemia, Myeloid
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Fludarabine
- Fludarabine phosphate
- Thiotepa
- Busulfan
Other Study ID Numbers
- P130916
- 2014-002109-39 (EUDRACT_NUMBER)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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