NCT00540995

Busulfan, Etoposide, and Intensity-Modulated Radiation Therapy Followed By Donor Stem Cell Transplant in Treating Patients With Advanced Myeloid Cancer

Phase I/II Study of Intravenous (IV) Busulfan and Etoposide (VP-16) Combined With Escalated Doses of Large Field Image-Guided Intensity Modulated Radiation Therapy (IMRT) Using Helical Tomotherapy as a Preparative Regimen for Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for Patients With Advanced Myeloid Malignancies

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 25 (actual)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 6 Years – 55 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Giving chemotherapy drugs, such as busulfan and etoposide, and intensity-modulated radiation therapy 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 intensity-modulated radiation therapy together with busulfan and etoposide before a 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 when given together with busulfan and etoposide followed by a donor stem cell transplant and to see how well it works in treating patients with advanced myeloid cancer.

Detailed description

OBJECTIVES: I. To establish the maximum tolerated dose (MTD) of a large field image-guided IMRT, using helical tomotherapy, when given in combination with IV busulfan and VP-16 as a preparative regimen for allogeneic hematopoietic stem cell transplantation (HSCT) from an HLA-identical sibling in patients with advanced myeloid malignancies. (Phase I) II. To describe the toxicities at each dose level studied. (Phase I) III. To estimate the radiation doses to the whole body, normal organs, and bone marrow through serial imaging studies following the administration of IMRT. (Phase I) IV. To estimate the overall survival probability, disease-free survival probability, and relapse rate associated with this preparative regimen. (Phase II) V. To characterize the treatment related mortality and toxicity profile (early/late) associated with this regimen. (Phase II) VI. To descriptively compare the outcomes of patients treated on this protocol to a comparable patient population conditioned with whole-body radiotherapy. (Phase II) OUTLINE: This is a phase I, dose-escalation study of intensity-modulated radiation therapy followed by a phase II study. PREPARATIVE CHEMOTHERAPY: Patients receive busulfan IV once daily over 2 hours on days -15 and -13 and then every 6 hours on days -12 to -9. Patients also receive etoposide IV on day -3. Patients undergo image-guided intensity-modulated radiation therapy using helical tomotherapy on days -8 to -5. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. GRAFT-VS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive GVHD prophylaxis that excludes methotrexate. After completion of study treatment, patients are followed periodically for 1 year and then annually for 2 years thereafter.

Conditions

• Adult Acute Myeloid Leukemia in Remission
• Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
• Adult Acute Myeloid Leukemia With Del(5q)
• Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
• Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
• Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
• Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
• Blastic Phase Chronic Myelogenous Leukemia
• Childhood Acute Myeloid Leukemia in Remission
• Childhood Chronic Myelogenous Leukemia
• Childhood Myelodysplastic Syndromes
• Previously Treated Myelodysplastic Syndromes
• Recurrent Adult Acute Myeloid Leukemia
• Recurrent Childhood Acute Myeloid Leukemia
• Refractory Anemia With Excess Blasts

Interventions

Type	Name	Description
DRUG	busulfan	Given IV
DRUG	etoposide	Given IV
RADIATION	intensity-modulated radiation therapy	Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses
PROCEDURE	allogeneic hematopoietic stem cell transplantation	Stem cell transplantation occurs on Day 0 after High Dose Therapy
PROCEDURE	allogeneic bone marrow transplantation	Stem cell transplantation occurs on Day 0 after High Dose Therapy
PROCEDURE	peripheral blood stem cell transplantation	Stem cell transplantation occurs on Day 0 after High Dose Therapy
RADIATION	tomotherapy	Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses

Timeline

• Start date: 2007-06-11
• Primary completion: 2011-05-17
• Completion: 2011-08-09
• First posted: 2007-10-08
• Last updated: 2023-11-30
• Results posted: 2021-11-22

Locations

1 site across 1 country: United States