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Trial record 4 of 126 for:    "Acute Leukemia" | "Antimetabolites, Antineoplastic"

Total Marrow and Lymphoid Irradiation and Chemotherapy for High-Risk Acute Leukemia

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ClinicalTrials.gov Identifier: NCT03408223
Recruitment Status : Recruiting
First Posted : January 23, 2018
Last Update Posted : January 23, 2018
Sponsor:
Information provided by (Responsible Party):
Chen Hu, Affiliated Hospital to Academy of Military Medical Sciences

Brief Summary:

RATIONALE: Giving chemotherapy and total marrow and lymphoid irradiation before allogeneic hematopoietic cell transplant helps stop the growth of leukemia cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may achieve brand new hematopoietic recovery. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells, resulting in graft versus-host disease.

PURPOSE: This study is to evaluate the toxicity and efficacy of total marrow and lymphoid irradiation conditioning when given together with combination chemotherapy and allogeneic peripheral blood stem cell transplant in treating patients with high-risk acute leukemia.


Condition or disease Intervention/treatment Phase
Acute Leukemia Radiation: total body irradiation Radiation: total marrow and lymphoid irradiation Not Applicable

Detailed Description:
Patient receives preparative therapy including cyclophosphamide and total body irradiation (TBI) of 10 Gy or total marrow and lymphoid irradiation (TMLI) of 12-20 Gy, and starts immunosuppressive therapy using cyclosporine or tacrolimus, methotrexate-based prophylaxes, followed by peripheral blood stem cell transplantation and granulocyte colony-stimulating factor administration.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Total Marrow and Lymphoid Irradiation and Chemotherapy Prior to Allogeneic Hematopoietic Cell Transplant for High-Risk Acute Leukemia
Actual Study Start Date : March 2014
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia

Arm Intervention/treatment
Active Comparator: total body irradiation
Patient receives preparative therapy including cyclophosphamide and total body irradiation (TBI) of 10 Gy on Days -4 through -1, and starts immunosuppressive therapy using cyclosporine or tacrolimus, methotrexate-based prophylaxes, followed by peripheral blood stem cell transplantation and granulocyte colony-stimulating factor administration.
Radiation: total body irradiation

Drug: Cyclophosphamide 60 mg/kg/day intravenous x 2 days pre-transplant, total dose 120 mg/kg

Drug: Cyclosporine or tacrolimus Beginning on Day -1 pre-transplant maintaining a level of 150-250 ng/ml or 5-10 ng/ml respectively. Cyclosporine or tacrolimus dosing will be monitored and altered as clinically appropriate by physician, and discontinue at approximately day + 180 post-transplant.

Drug: Methotrexate 15 mg/m2 intravenous on days 1, 10 mg/m2 intravenous on days 3, 6 and 11 after transplantation.

Intervention: Total Body Irradiation Dose of 10 Gy TBI (fraction size of 5 Gy given once a day on days -2 and -1).

Procedure: Peripheral blood stem cell transplantation product will be infused via intravenous drip on Day 0.

Other Name: TBI

Experimental: total marrow and lymphoid irradiation
Patient receives preparative therapy including cyclophosphamide and total marrow and lymphoid irradiation of 12-20 Gy on Days -8 through -2, and starts immunosuppressive therapy using cyclosporine or tacrolimus, methotrexate-based prophylaxes, followed by peripheral blood stem cell transplantation and granulocyte colony-stimulating factor administration.
Radiation: total marrow and lymphoid irradiation

Drug: Cyclophosphamide 60 mg/kg/day intravenous x 2 days pre-transplant, total dose 120 mg/kg

Drug: Cyclosporine or tacrolimus Beginning on Day -1 pre-transplant maintaining a level of 150-250 ng/ml or 5-10 ng/ml respectively. Cyclosporine or tacrolimus dosing will be monitored and altered as clinically appropriate by physician, and discontinue at approximately day + 180 post-transplant.

Drug: Methotrexate 15 mg/m2 intravenous on days 1, 10 mg/m2 intravenous on days 3, 6 and 11 after transplantation.

Intervention: Total Marrow and Lymphoid Irradiation Dose of 12-20 Gy TMLI (fraction size of 4 Gy given once a day).

Procedure: Peripheral blood stem cell transplantation product will be infused via intravenous drip on Day 0.

Other Name: TMLI




Primary Outcome Measures :
  1. Incidence of toxicity, scored on National Cancer Institute Common Terminology Criteria version 4.03 [ Time Frame: Up to 100 days after stem cell infusion ]
    Toxicity information recorded will include the type, severity, and the probable association with the study regimen.

  2. Progression-Free Survival (PFS) [ Time Frame: The time from start of protocol therapy to death, relapse/progression, or last follow-up, whichever comes first, assessed up to 2 years ]
    Calculated using the Kaplan-Meier method. The cumulative incidence of relapse/progression will be calculated as a competing risk using the Gray method.


Secondary Outcome Measures :
  1. Incidence of transplantation-related mortality [ Time Frame: 6 months ]
    In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.

  2. Incidence of grade II-IV acute graft-versus-host disease (GVHD) after transplantation [ Time Frame: Day +100 ]
    Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.

  3. Incidence of chronic GVHD after transplantation [ Time Frame: 1 Year ]
    Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.

  4. Incidence of relapse after transplantation [ Time Frame: 1 year and 2 years ]
    The return of disease after its apparent recovery/cessation.

  5. Menstrual recovery after transplantation [ Time Frame: 1 year and 2 years ]
    The percentage of female patients who have resumed menses is usually considered as related to ovarian function.

  6. Overall survival after transplantation [ Time Frame: The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. ]
    1 year and 2 years



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Ages Eligible for Study:   8 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. High-risk acute myelogenous leukemia or acute lymphocytic leukemia based on clinical and biological characteristics, which including but not limited to poor response to induction therapy and relapse or beyond second remission.
  2. Karnofsky performance status (KPS) >= 70%
  3. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
  4. All candidates for this study must have a prepared allogeneic stem cell donor, including human leukocyte antigen matched or partially mismatched donor
  5. A cardiac evaluation with an electrocardiogram showing no ischemic changes or abnormal rhythm and an ejection fraction of >= 50% established by multi gated acquisition scan (MUGA) or echocardiogram
  6. Patients must have a serum creatinine of less than or equal to 1.3 mg/dL or creatinine clearance >70 ml/min
  7. Hepatic: bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), Alkaline phosphatase (ALP) < 5 x upper limit of normal (ULN)
  8. Pulmonary function: Carbon Monoxide Diffusing Capacity corrected (DLCOcorr) > 50% of normal, (oxygen saturation [>92%] can be used in child where pulmonary function tests (PFT's) cannot be obtained)
  9. The time from the end last induction or re-induction attempt should be greater than or equal to 14 days
  10. All subjects must have the ability to understand and the willingness to sign a written informed consent

Exclusion Criteria:

  1. Active uncontrolled infection at time of enrollment or documented fungal infection within 3 months
  2. Evidence of Human immunodeficiency virus (HIV) infection
  3. Prior myeloablative transplant within the last 6 months
  4. Prior radiation therapy that would exclude the use of TMLI
  5. Relapsed patients who have undergone autologous or allogeneic hematopoietic stem cell transplantation previously

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): NCT03408223


Contacts
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Contact: Xiao Lou, M.D., Ph.D. +8610-66947122 louxiao@163.com

Locations
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China, Beijing
Affiliated Hospital to Academy of Military Medical Sciences (307 Hospital of PLA) Recruiting
Beijing, Beijing, China, 100071
Contact: Xiao Lou, M.D., Ph.D.    +8610-66947122    louxiao@163.com   
Sponsors and Collaborators
Affiliated Hospital to Academy of Military Medical Sciences
Investigators
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Principal Investigator: Hu Chen, M.D., Ph.D. Affiliated Hospital to Academy of Military Medical Sciences (307 Hospital of PLA)

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Responsible Party: Chen Hu, Principal Investigator, Affiliated Hospital to Academy of Military Medical Sciences
ClinicalTrials.gov Identifier: NCT03408223     History of Changes
Other Study ID Numbers: LouX02
First Posted: January 23, 2018    Key Record Dates
Last Update Posted: January 23, 2018
Last Verified: January 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Antimetabolites, Antineoplastic
Leukemia
Acute Disease
Neoplasms by Histologic Type
Neoplasms
Disease Attributes
Pathologic Processes
Cyclosporine
Cyclophosphamide
Methotrexate
Tacrolimus
Cyclosporins
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Calcineurin Inhibitors