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

Myelodysplastic Syndromes Clinical Trial

Official title:

Total Marrow and Lymphoid Irradiation and Chemotherapy Prior to Allogeneic Hematopoietic Cell Transplant for Myelodysplastic Syndrome or Acute Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03408210
• Other study ID #: LouX01
• Status: Recruiting
• Phase: N/A
• First received: December 24, 2017
• Last updated: January 16, 2018
• Start date: March 2014
• Est. completion date: August 2022

Study information

• Verified date: January 2018
• Source: Affiliated Hospital to Academy of Military Medical Sciences
• Contact: Xiao Lou, M.D., Ph.D.
• Phone: +8610-66947122
• Email: louxiao[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 191
• Est. completion date: August 2022
• Est. primary completion date: March 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Disease
• Acute Leukemia
• Leukemia
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

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.
• 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.

Locations

Country	Name	City	State
China	Affiliated Hospital to Academy of Military Medical Sciences (307 Hospital of PLA)	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Affiliated Hospital to Academy of Military Medical Sciences

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Incidence of grade II-IV acute graft-versus-host disease (GVHD) after transplantation	Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.	Day +100
Secondary	Incidence of chronic GVHD after transplantation	Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.	1 Year
Secondary	Menstrual recovery after transplantation	The percentage of female patients who have resumed menses is usually considered as related to ovarian function.	1 Year and 2 years
Secondary	Overall survival after transplantation	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