Using targeted radiation and chemotherapy before a donor transplant for acute myeloid leukemia
Pilot Study of Total Marrow/Lymphoid Irradiation (TMLI) Conditioning Prior to Allogeneic Hematopoietic Stem Cell Transplant (HCT) Followed by Post Transplant Cyclophosphamide-Based Graft Versus Host Disease Prophylaxis for Acute Myelogenous Leukemia in Complete Remission
PHASE1 · City of Hope Medical Center · NCT03467386
This study is testing a combination of targeted radiation and chemotherapy before a donor transplant to see if it helps people with acute myeloid leukemia avoid complications and improve their recovery.
Quick facts
| Phase | PHASE1 |
|---|---|
| Study type | Interventional |
| Enrollment | 18 (estimated) |
| Ages | 16 Years to 60 Years |
| Sex | All |
| Sponsor | City of Hope Medical Center (other) |
| Drugs / interventions | chemotherapy, radiation, cyclophosphamide |
| Locations | 1 site (Duarte, California) |
| Trial ID | NCT03467386 on ClinicalTrials.gov |
What this trial studies
This pilot phase I trial evaluates the safety and feasibility of combining total marrow and lymphoid irradiation (TMLI) with high-dose cyclophosphamide as a preventive measure against graft-versus-host disease (GvHD) in patients with acute myeloid leukemia (AML). The study focuses on patients in their first or second complete remission and aims to assess various outcomes including adverse events, incidence of GvHD, overall survival, and quality of life post-transplant. By targeting cancer in the bone marrow and blood, this approach seeks to improve treatment efficacy while minimizing side effects. Participants will undergo allogeneic hematopoietic stem cell transplantation followed by cyclophosphamide treatment.
Who should consider this trial
Good fit: Ideal candidates are patients with acute myeloid leukemia in first or second complete remission and with a suitable HLA-matched sibling donor.
Not a fit: Patients who are not in remission or do not have an HLA-matched sibling donor may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could enhance treatment outcomes and reduce complications for patients with acute myeloid leukemia undergoing stem cell transplantation.
How similar studies have performed: While this approach is innovative, similar studies have shown promise in improving outcomes for patients undergoing stem cell transplantation.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * This study is open to patients with acute myeloid leukemia (AML) evaluated within 30 days of the start of conditioning regimen and in first or second complete remission (CR) * Karnofsky performance status (KPS) \>= 70% * The effects of radiation on the developing fetus are known to be teratogenic; for this reason, 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 * Patients with acute myelogenous leukemia (AML) who are in first or second complete remission * All candidates for this study must have a human leukocyte antigen (HLA) (A, B, C, DR) identical sibling who is willing to donate primed blood stem cells (preferred) or bone marrow, or have a 10/10 allele matched unrelated donor; 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 \> 70 ml/min as calculated by the Cockcroft-Gault formula * A bilirubin of less than or equal to 1.5 mg/dL, excluding patients with Gilbert's disease * Patients should also have a serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) less than 5 times the upper limit of normal * Pulmonary function tests including diffusing capacity of the lung for carbon monoxide (DLCO) will be performed; forced expiratory volume in 1 second (FEV 1) and DLCO should be greater than 50% of predicted normal value * All subjects must have the ability to understand and the willingness to sign a written informed consent; signed informed consent form approved by the Institutional Review Board (IRB) is required; the patient, family member, and transplant staff physician (physician, nurse, and social worker) meet at least once prior to starting the transplant procedure; during this meeting, all pertinent information with respect to risks and benefits to the donor and recipient will be presented; alternative treatment modalities will be discussed * The time from the end of last induction, re-induction, or consolidation regimen should be greater than or equal to 14 days * Prior therapy with etoposide and cyclophosphamide is allowed * DONOR: donor evaluation and eligibility will be assessed as per current City of Hope standard operating procedure (SOP) Exclusion Criteria: * Patients should not have any uncontrolled illness including ongoing or active or poorly controlled infection * Patients may not be receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy; maintenance therapy with Food and Drug Administration (FDA)-approved targeted therapies (e.g. tyrosine kinase inhibitors for Philadelphia chromosome \[Ph\] positive \[+\] acute lymphoblastic leukemia \[ALL\], and FLT inhibitors for FLT3+ patients) will be allowed after day 60 disease assessment * Prior radiation therapy that would exclude the use of TMLI * Relapsed patients who have undergone autologous or allogeneic hematopoietic stem cell transplantation previously * Patients with psychological or medical condition that patient's physician deems unacceptable to proceed to allogeneic hematopoietic stem cell transplantation * Electrocardiogram (EKG) showing ischemic changes or abnormal rhythm and/or an echocardiogram or MUGA scan showing abnormal wall motion or ejection fraction \< 50% * Patients who have been treated with chemotherapy or radiation for the purpose of induction, re-induction or consolidation, within two weeks of planned study enrollment * Patients with other active malignancies are ineligible for this study, other than localized malignancies * Patients that are pregnant or breastfeeding * Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, including but not limited to, infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc. * Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
Where this trial is running
Duarte, California
- City of Hope Medical Center — Duarte, California, United States (RECRUITING)
Study contacts
- Principal investigator: Anthony S Stein — City of Hope Comprehensive Cancer Center
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions: Acute Myeloid Leukemia