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Trial record 25 of 126 for:    "Acute Leukemia" | "Antimetabolites, Antineoplastic"

GVHD Prophylaxis With Post-transplantation Bendamustine in Refractory Leukemia

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ClinicalTrials.gov Identifier: NCT02799147
Recruitment Status : Recruiting
First Posted : June 14, 2016
Last Update Posted : April 5, 2019
Sponsor:
Information provided by (Responsible Party):
Ivan S Moiseev, St. Petersburg State Pavlov Medical University

Brief Summary:
Several groups have demonstrated very low incidence of acute and chronic graft-versus-host disease (GVHD) with post-transplantation cyclophosphamide (PTCy) in haploidentical, unrelated and related allogeneic stem cell transplantation (SCT). Nonetheless for majority of the grafts, except for 10/10 HLA-matched bone marrow, with this type of prophylaxis require concomitant administration of calcineurin inhibitors±MMF, which delays immune reconstitution and development of graft-versus-leukemia (GVL) effect. So, despite reduction of transplant-related mortality, use of PTCy doesn't lead to the reduction of relapse incidence. This is particularly important for relapsed or refractory acute leukemia patients, where, despite all efforts to intensify conditioning regimens, relapses after SCT occur in more than 50% of patients, and long-term survival rarely exceeds 10-20%. In preclinical model of haploidentical SCT the substitution of post-transplantation cyclophosphamide with bendamustine, led to comparable GVHD control, but significantly augmented GVL effect. To test this hypothesis and improve the outcome of allogeneic SCT in refractory acute leukemia patients we initiated a pilot trial with high-dose post-transplantation bendamustine for GVHD prophylaxis. The selection of doses is based on the previous dose-escalation studies. Additional immunosuppression could be added for mismatched grafts.

Condition or disease Intervention/treatment Phase
Leukemia, Acute Lymphoblastic Acute Myeloid Leukemia Mixed-Lineage Acute Leukemias Procedure: Allogeneic stem cell transplantation Drug: Fludarabine monophosphate Drug: Busulfan Drug: Bendamustine Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Dose-escalation Study of Graft-versus-host Disease Prophylaxis With High-dose Post-transplantation Bendamustine in Patients With Refractory Acute Leukemia
Actual Study Start Date : June 2016
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2020


Arm Intervention/treatment
Experimental: 280 mg/m2 bendamustine
10 patients Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days Days -6 through -3: Busulfan 1 mg/kg po qid №14 Day 0: Infusion of unmanipulated graft Day +3 and +4: Bendamustine 140 mg/m2/day iv.
Procedure: Allogeneic stem cell transplantation
Other Name: HSCT

Drug: Fludarabine monophosphate
Drug: Busulfan
Drug: Bendamustine
Experimental: 200 mg/m2 bendamustine
10 patients Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days Days -6 through -3: Busulfan 1 mg/kg po qid №14 Day 0: Infusion of unmanipulated graft Day +3 and +4: Bendamustine 100 mg/m2/day iv
Procedure: Allogeneic stem cell transplantation
Other Name: HSCT

Drug: Fludarabine monophosphate
Drug: Busulfan
Drug: Bendamustine
Experimental: 140 mg/m2 bendamustine
10 patients Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days Days -6 through -3: Busulfan 1 mg/kg po qid №14 Day 0: Infusion of unmanipulated graft Day +3, +4: Bendamustine 70 mg/m2/day iv.
Procedure: Allogeneic stem cell transplantation
Other Name: HSCT

Drug: Fludarabine monophosphate
Drug: Busulfan
Drug: Bendamustine



Primary Outcome Measures :
  1. Engraftment rate [ Time Frame: 60 days ]
    Engraftment is defined as the first of 3 consecutive days with an ANC>500 per μl and WBC>1000 per μl. Platelet engraftment is not mandatory for the endpoint.


Secondary Outcome Measures :
  1. Relapse rate analysis [ Time Frame: 365 days ]
  2. Non-relapse mortality analysis [ Time Frame: 365 days ]
  3. Incidence of acute GVHD, grades II-IV [ Time Frame: 180 days ]
  4. Incidence of chronic GVHD, moderate and severe (NIH criteria) [ Time Frame: 365 days ]
  5. Overall survival analysis [ Time Frame: 365 days ]
  6. Event-free survival analysis [ Time Frame: 365 days ]
  7. Toxicity (NCI CTCAE 4.03) [ Time Frame: 100 days ]
    Toxicity parameters based on NCI CTCAE 4.03 grades: hepatotoxicity (liver function tests), nephrotoxicity (creatinine), neurotoxicity (attending physician assessment), mucositis (attending physician assessment), hemorrhagic cystitis (attending physician assessment), cardiotoxicity (ECG, echocardiography). Additional toxicity parameters: incidence and severity of veno-occlusive disease, incidence of transplant-associated microangiopathy

  8. Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence [ Time Frame: 100 days ]


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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

- Diagnosis: Acute Myeloblastic Leukemia Acute Lymphoblastic Leukemia Mixed-Lineage Acute Leukemias

  • Disease, refractory to at list one course of induction chemotherapy or immunotherapy
  • More than 5% clonal blasts in the bone marrow or peripheral blood at the time of inclusion
  • Signed informed consent
  • Matched related, 8-10/10 HLA-matched unrelated or haploidentical donor available. The HLA typing is performed by the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1.
  • No second tumors
  • No severe concurrent illness
  • No previous autologous or allogeneic stem cell transplantations

Exclusion Criteria:

  • Karnofsky index <70%
  • Moderate or severe cardiac dysfunction, left ventricular ejection fraction <50%
  • Moderate or severe decrease in pulmonary function, FEV1 <70% or DLCO<70% of predicted
  • Respiratory distress >grade I
  • Severe organ dysfunction: AST or ALT >5 upper normal limits, bilirubin >1.5 upper normal limits, creatinine >1.5 upper normal limits
  • Creatinine clearance < 60 mL/min
  • Uncontrolled bacterial or fungal infection at the time of enrollment, defined by CRP level >70 mg/L or positive procalcitonin in patient with adequate empirical antibacterial and antifungal therapy.
  • Requirement for vasopressor support at the time of enrollment
  • Pregnancy
  • Somatic or psychiatric disorder making the patient unable to sign informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02799147


Contacts
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Contact: Boris V. Afanasyev, Professor +78122334551 coordinatorbmt@gmail.com
Contact: Ivan S. Moiseev, PhD +79217961951 moisiv@mail.ru

Locations
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Russian Federation
First Pavlov State Medical University of St. Petersburg Recruiting
Saint-Petersburg, Russian Federation, 197089
Contact: Ivan S. Moiseev, PhD    +79217961951    moisiv@mail.ru   
Contact: Olga A. Slesarchuk, PhD    +79111910003    olga.slesarchuk@gmail.com   
Sub-Investigator: Olga V. Pirogova, M.S.         
Sponsors and Collaborators
St. Petersburg State Pavlov Medical University
Investigators
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Study Director: Boris V. Afanasyev, Professor St. Petersburg State Pavlov Medical University

Publications:
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Responsible Party: Ivan S Moiseev, Vice-director for science of R.M. Gorbacheva Memorial Institute of Hematology, Oncology and Transplantation, St. Petersburg State Pavlov Medical University
ClinicalTrials.gov Identifier: NCT02799147     History of Changes
Other Study ID Numbers: 05/16-n
First Posted: June 14, 2016    Key Record Dates
Last Update Posted: April 5, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Consultations are ongoing about how IPD initiative fits the local law "About personal data 152-fz".
Keywords provided by Ivan S Moiseev, St. Petersburg State Pavlov Medical University:
Mixed-Lineage Acute Leukemias
Allogeneic Transplantation
Hematopoietic Stem Cell Transplantation
Leukemia, Acute Lymphoblastic
Acute Myeloid Leukemia
Immune System Diseases
Immunosuppressive Agents
Myeloablative Agonists
Busulfan
Fludarabine
Antineoplastic Agents, Alkylating
Bendamustine Hydrochloride
Additional relevant MeSH terms:
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Antimetabolites, Antineoplastic
Leukemia
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Biphenotypic, Acute
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Vidarabine
Fludarabine
Fludarabine phosphate
Busulfan
Bendamustine Hydrochloride
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Alkylating Agents
Antineoplastic Agents, Alkylating
Myeloablative Agonists