Intensity-Modulated Radiation Therapy, Etoposide, and Cyclophosphamide Followed By Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia
Phase I-II Study of Escalating Doses of Large Field Image-Guided Intensity Modulated Radiation Therapy (IMRT) Using Helical Tomotherapy in Combination With Etoposide (VP16) and Cytoxan as a Preparative Regimen for Allogeneic Hematopoietic Stem Cell (HSC) Transplantation for Patients With Poor Risk Acute Lymphocytic Leukemia (ALL) or Poor Risk Acute Myelogenous Leukemia (AML)
5 other identifiers
interventional
51
1 country
1
Brief Summary
RATIONALE: Giving intensity modulated radiation therapy (IMRT) and chemotherapy, such as etoposide and cyclophosphamide, before a donor stem cell transplant helps stop the growth of cancer cells. It also helps 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 help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving IMRT together with chemotherapy before transplant may stop this from happening. PURPOSE: This phase I/II trial is studying the side effects and best dose of intensity-modulated radiation therapy (IMRT) when given together with etoposide and cyclophosphamide followed by donor stem cell transplant and to see how well they work in treating patients with relapsed or refractory acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 leukemia
Started Mar 2008
Longer than P75 for phase_1 leukemia
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 18, 2007
CompletedFirst Posted
Study publicly available on registry
December 19, 2007
CompletedStudy Start
First participant enrolled
March 4, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 30, 2016
CompletedResults Posted
Study results publicly available
April 11, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
January 7, 2026
CompletedMarch 24, 2026
March 1, 2026
8.2 years
December 18, 2007
February 1, 2023
March 11, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Maximum Tolerated Dose of Intensity-modulated Radiotherapy (Phase I)
Toxicities will be recorded using two distinct grading systems: the modified Bearman scale and the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 3.0 scale.
30 days post transplant
Study Arms (9)
Level 1: 1200cGy
EXPERIMENTAL150cGy BID x Days 1-4. Total dose 1200cGy.
Level 2: 1350cGy
EXPERIMENTAL150cGy BID Day 1-4 then 150 cGy QD Day 5. Total dose 1350cGy.
Level 3: 1500cGy limited dose to ribs, sternum, liver, brain 1200cGy
EXPERIMENTAL150cGy BID Day 1-5. Total dose 1500Gy.
Level 4: 1500cGy limited dose to liver, brain 1200cGy
EXPERIMENTAL150cGy BID Day 1-5. Total dose 1500Gy.
Level 5: 1600cGy limited dose to liver, porta-hepatic, brain 1200cGy
EXPERIMENTAL160cGy BID Day 1-5. Total dose 1600Gy.
Level 6: 1700cGy limited dose to liver, porta-hepatic, brain 1200cGy
EXPERIMENTAL170cGy BID Day 1-5. Total dose 1700Gy.
Level 7: 1800cGy limited dose to liver, porta-hepatic, brain 1200cGy
EXPERIMENTAL180cGy BID Day 1-5. Total dose 1800Gy.
Level 8: 1900cGy limited dose to liver, porta-hepatic, brain 1200cGy
EXPERIMENTAL190cGy BID Day 1-5. Total dose 1900Gy.
Level 9: 2000cGy limited dose to liver, porta-hepatic, brain 1200cGy
EXPERIMENTAL200cGy BID Day 1-5. Total dose 2000Gy.
Interventions
Given IV
Given IV
Occurs approximately 48 hours after completion of cyclophosphamide
Occurs approximately 48 hours after completion of cyclophosphamide
Occurs approximately 48 hours after completion of cyclophosphamide
Undergo IMRT
Undergo IMRT using helical tomotherapy
Eligibility Criteria
You may qualify if:
- Patients with acute lymphocytic leukemia or acute myelogenous leukemia who are not in first or second remission (i.e., after failing remission induction therapy or in relapse or beyond second remission)
- All candidates for this study must have a human leukocyte antigen (HLA) (A, B, C, DR) identical sibling who is willing to donate bone marrow or 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 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
- Prior therapy with VP-16, Busulfan, and Cytoxan is allowed
- 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 1.2 or creatinine clearance \> 80 ml/min
- A bilirubin of less than or equal to 1.5
- Serum glutamic oxaloacetic transaminase (SGOT) less than 5 times the upper limit of normal
- Serum glutamate pyruvate transaminase (SGPT) less than 5 times the upper limit of normal
- Pulmonary functioning tests including diffusing capacity of carbon monoxide (DLCO) will be performed; forced expiratory volume in one second (FEV1) and DLCO should be greater than 50% of the predicted normal value
- The time from the end last induction or reinduction attempt should be \>= 14 days
- Signed informed consent form approved by the Institutional Review Board (IRB) is required
- DONOR: Any sibling donors who are histocompatible with the prospective recipient will be considered a suitable donor
- Donors will be excluded if for psychological or medical reasons they are unable to tolerate the procedure
- Donor should be able to donate peripheral blood stem cells or bone marrow
You may not qualify if:
- Prior radiation therapy that would exclude the use of total-body irradiation
- Patients who have undergone bone marrow transplantation previously and who have relapsed
- Patients with psychological or medical condition that patients physician deems unacceptable to proceed to allogeneic bone marrow transplant
- Pregnancy
- Electrocardiogram (EKG) showing ischemic changes or abnormal rhythm and/or an echocardiogram or MUGA scan showing abnormal wall motion or ejection fraction \< 50%
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- City of Hope Medical Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
City of Hope Medical Center
Duarte, California, 91010-3000, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Anthony Stein, MD, corresponding author
- Organization
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope
Study Officials
- STUDY CHAIR
Anthony S. Stein, MD
City of Hope Medical Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 18, 2007
First Posted
December 19, 2007
Study Start
March 4, 2008
Primary Completion
May 30, 2016
Study Completion
January 7, 2026
Last Updated
March 24, 2026
Results First Posted
April 11, 2023
Record last verified: 2026-03