NCT03408210

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 myelodysplastic syndrome or acute leukemia.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
191

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Mar 2014

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2014

Completed
3.8 years until next milestone

First Submitted

Initial submission to the registry

December 24, 2017

Completed
1 month until next milestone

First Posted

Study publicly available on registry

January 23, 2018

Completed
1 month until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2018

Completed
4.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2022

Completed
Last Updated

January 23, 2018

Status Verified

January 1, 2018

Enrollment Period

4 years

First QC Date

December 24, 2017

Last Update Submit

January 16, 2018

Conditions

Myelodysplastic SyndromesAcute Leukemia

Outcome Measures

Primary Outcomes (2)

  • Incidence of toxicity, scored on National Cancer Institute Common Terminology Criteria version 4.03

    Toxicity information recorded will include the type, severity, and the probable association with the study regimen.

    Up to 100 days after stem cell infusion

  • Hematopoietic reconstruction

    Neutrophil engraftment is defined as the first day of three consecutive days where the neutrophil count (absolute neutrophil count) is 1,000 cells/mm3 (1.0×109/L) or greater. Platelet engraftment is defined as 20,000/mm3 (20×109/L) for 3 consecutive days unsupported by a platelet transfusion.

    Day +30

Secondary Outcomes (4)

  • Incidence of grade II-IV acute graft-versus-host disease (GVHD) after transplantation

    Day +100

  • Incidence of chronic GVHD after transplantation

    1 Year

  • Menstrual recovery after transplantation

    1 Year and 2 years

  • Overall survival after transplantation

    1 year and 2 years

Study Arms (2)

total body irradiation

ACTIVE COMPARATOR

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

total marrow and lymphoid irradiation

EXPERIMENTAL

Patient receives preparative therapy including cyclophosphamide and total marrow and lymphoid irradiation of 12 Gy on Days -6 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

Interventions

total body irradiationRADIATION

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.

Also known as: TBI
total body irradiation
total marrow and lymphoid irradiationRADIATION

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 Gy TMLI (fraction size of 4 Gy given once a day on days -6, -5 and -4). Procedure: Peripheral blood stem cell transplantation product will be infused via intravenous drip on Day 0.

Also known as: TMLI
total marrow and lymphoid irradiation

Eligibility Criteria

Age8 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Myelodysplastic syndrome with excess blasts: Cytopenias, Unilineage or multilineage dysplasia, 5-19% blasts in bone marrow.
  • Acute lymphocytic leukemia or acute myelogenous leukemia who are in first remission or second remission.
  • Karnofsky performance status (KPS) \>= 70%
  • 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
  • All candidates for this study must have a human leukocyte antigen (HLA) (A, B, C, DR) identical siblings who is willing to donate primed blood stem cells or a 10/10 allele matched unrelated donor; a single allele mismatch at A, B, C, DR or DQ and a killer immunoglobulin-like receptor (KIR) mismatch at C will be allowed; all ABO blood group combinations of the donor/recipient are acceptable since even major ABO compatibilities can be dealt with by various techniques (red cell exchange or plasma exchange)
  • 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
  • Patients must have a serum creatinine of less than or equal to 1.3 mg/dL or creatinine clearance \> 80 ml/min
  • Hepatic: bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), Alkaline phosphatase (ALP) \< 5 x upper limit of normal (ULN)
  • 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)
  • The time from the end last induction or re-induction attempt should be greater than or equal to 14 days
  • All subjects must have the ability to understand and the willingness to sign a written informed consent

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Affiliated Hospital to Academy of Military Medical Sciences (307 Hospital of PLA)

Beijing, Beijing Municipality, 100071, China

RECRUITING

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Whole-Body IrradiationLymphatic Irradiation

Condition Hierarchy (Ancestors)

Bone Marrow DiseasesHematologic DiseasesHemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

RadiotherapyTherapeuticsInvestigative Techniques

Study Officials

  • Hu Chen, M.D., Ph.D.

    Affiliated Hospital to Academy of Military Medical Sciences (307 Hospital of PLA)

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiao Lou, M.D., Ph.D.

CONTACT

+8610-66947122louxiao@163.com

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

December 24, 2017

First Posted

January 23, 2018

Study Start

March 1, 2014

Primary Completion

March 1, 2018

Study Completion

August 1, 2022

Last Updated

January 23, 2018

Record last verified: 2018-01

Locations

CN(1)