Clinical trial NCT03408223: Total Marrow and Lymphoid Irradiation and Chemotherapy for High-Risk Acute Leukemia
Official title: Total Marrow and Lymphoid Irradiation and Chemotherapy Prior to Allogeneic Hematopoietic Cell Transplant for High-Risk Acute Leukemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Acute Leukemia
Lead sponsor: Affiliated Hospital to Academy of Military Medical Sciences
Sponsor class: OTHER
First posted: 2018-01-23
Enrollment: 100
Sex: ALL
Minimum age (years): 8
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Incidence of toxicity, scored on National Cancer Institute Common Terminology Criteria version 4.03
timeFrame: Up to 100 days after stem cell infusion
measure: Progression-Free Survival (PFS)
timeFrame: The time from start of protocol therapy to death, relapse/progression, or last follow-up, whichever comes first, assessed up to 2 years
Secondary outcomes:
measure: Incidence of transplantation-related mortality
timeFrame: 6 months
measure: Incidence of grade II-IV acute graft-versus-host disease (GVHD) after transplantation
timeFrame: Day +100
measure: Incidence of chronic GVHD after transplantation
timeFrame: 1 Year
measure: Incidence of relapse after transplantation
timeFrame: 1 year and 2 years
measure: Menstrual recovery after transplantation
timeFrame: 1 year and 2 years
measure: Overall survival after transplantation
timeFrame: 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.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Affiliated Hospital to Academy of Military Medical Sciences (307 Hospital of PLA)
state: Beijing
Study officials:
affiliation: Affiliated Hospital to Academy of Military Medical Sciences (307 Hospital of PLA)
name: Hu Chen, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: