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

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

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.

Study Overview

• Status: Unknown
• Conditions: Myelodysplastic Syndromes; Acute Leukemia
• Intervention / Treatment: Radiation: total body irradiation; Radiation: total marrow and lymphoid irradiation

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.

• Study Type: Interventional
• Enrollment (Anticipated): 191
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiao Lou, M.D., Ph.D.; Phone Number: +8610-66947122; Email: louxiao@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100071
      • Recruiting
      • Affiliated Hospital to Academy of Military Medical Sciences (307 Hospital of PLA)
      • Contact: Xiao Lou, M.D., Ph.D.; Phone Number: +8610-66947122; Email: louxiao@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: TBI
Experimental: 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.	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.; Other Names: TMLI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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

Collaborators and Investigators

• Sponsor: Affiliated Hospital to Academy of Military Medical Sciences
• Investigators: Principal Investigator: Hu Chen, M.D., Ph.D., Affiliated Hospital to Academy of Military Medical Sciences (307 Hospital of PLA)

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2014
• Primary Completion (Anticipated): March 1, 2018
• Study Completion (Anticipated): August 1, 2022

Study Registration Dates

• First Submitted: December 24, 2017
• First Submitted That Met QC Criteria: January 16, 2018
• First Posted (Actual): January 23, 2018

Study Record Updates

• Last Update Posted (Actual): January 23, 2018
• Last Update Submitted That Met QC Criteria: January 16, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Leukemia; Preleukemia; Acute Disease
• Other Study ID Numbers: LouX01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No