Total Marrow and Lymphoid Irradiation and Chemotherapy for Myelodysplastic Syndrome or Acute Leukemia

NCT ID: NCT03408210

Last Updated: 2018-01-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

191 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-03-31

Study Completion Date

2022-08-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Myelodysplastic Syndromes Acute Leukemia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

total body irradiation

Intervention Type RADIATION

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.

total marrow and lymphoid irradiation

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.

Group Type EXPERIMENTAL

total marrow and lymphoid irradiation

Intervention Type RADIATION

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.

Interventions

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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.

Intervention Type 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 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.

Intervention Type RADIATION

Other Intervention Names

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TBI TMLI

Eligibility Criteria

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Inclusion Criteria

1. Myelodysplastic syndrome with excess blasts: Cytopenias, Unilineage or multilineage dysplasia, 5-19% blasts in bone marrow.
2. Acute lymphocytic leukemia or acute myelogenous leukemia who are in first remission or second remission.
3. Karnofsky performance status (KPS) \>= 70%
4. 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
5. 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)
6. 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
7. Patients must have a serum creatinine of less than or equal to 1.3 mg/dL or creatinine clearance \> 80 ml/min
8. Hepatic: bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), Alkaline phosphatase (ALP) \< 5 x upper limit of normal (ULN)
9. 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)
10. The time from the end last induction or re-induction attempt should be greater than or equal to 14 days
11. All subjects must have the ability to understand and the willingness to sign a written informed consent

Exclusion Criteria

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

8 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Affiliated Hospital to Academy of Military Medical Sciences

OTHER

Sponsor Role lead

Responsible Party

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Chen Hu

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Hu Chen, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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

Beijing, Beijing Municipality, China

Site Status RECRUITING

Countries

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China

Central Contacts

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

Role: CONTACT

+8610-66947122

Facility Contacts

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

Role: primary

+8610-66947122

Other Identifiers

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LouX01

Identifier Type: -

Identifier Source: org_study_id

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