Busulfan, Etoposide, and Total-Body Irradiation in Treating Patients Undergoing Donor Stem Cell or Bone Marrow Transplant for Advanced Hematologic Cancer

NCT00534430 | Active Not Recruiting Phase 2 Results

• 4 other identifiers: 99041P30CA033572CHNMC-99041CDR0000564777
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

RATIONALE: Giving chemotherapy and total-body irradiation before a donor stem cell transplant or a donor bone marrow transplant helps stop the growth of cancer and abnormal cells and 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 mycophenolate mofetil and cyclosporine before and after transplant may stop this from happening. PURPOSE: This phase II trial is studying the side effects and best way to give busulfan together with etoposide and total-body irradiation and to see how well they work in treating patients who are undergoing a donor stem cell or bone marrow transplant for advanced hematologic cancer.

Conditions

Leukemia; Myelodysplastic Syndromes

Keywords

adult acute myeloid leukemia with 11q23 (MLL) abnormalities; 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); recurrent adult acute myeloid leukemia; adult acute myeloid leukemia in remission; recurrent childhood acute myeloid leukemia; recurrent adult acute lymphoblastic leukemia; recurrent childhood acute lymphoblastic leukemia; blastic phase chronic myelogenous leukemia; refractory anemia with excess blasts in transformation; refractory anemia with excess blasts; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes

Outcome Measures

Primary Outcomes (4)

• Overall Survival at 5 Years Post-Transplant.

  Kaplan-Meier estimate of an event of death estimated at five years post-transplant. 95% confidence intervals were calculated from the logit transform of the Greenwood variance. The transformation was necessary to keep the estimate within the probability space of 0 to 100%.

  Date of Transplant to Five Years post-Transplant

• Disease-free Survival at Five Years Post-transplant

  Kaplan-Meier estimate of an event of relapse or death estimated at five years post-transplant. 95% confidence intervals were calculated from the logit transform of the Greenwood variance. The transformation was necessary to keep the estimate within the probability space of 0 to 100%.

  Date of transplant to five years post-transplant

• Overall Survival Comparing Diagnosis Groups

  Kaplan-Meier estimate of an event of death estimated at five years post-transplant. 95% confidence intervals were calculated from the logit transform of the Greenwood variance. The transformation was necessary to keep the estimate within the probability space of 0 to 100%.

  Date of Transplant to Five Years post-Transplant

• Cumulative Incidence of Relapse With Transplant-related Death as the Competing Risk: Diagnosis Groups Are Compared.

  Fine and Gray estimate of cumulative incidence of Relapse, with Death as the competing risk. Estimate is at five years post-transplant. Ninety-five percent confidence interval is by logit transformation of Greenwood variance to keep the interval within the probability space of 0% to 100%.

  Date of Transplant to Five Years post-Transplant. Estimate is at Five Years post-Transplant.

Study Arms (1)

Busulfan, FTBI and VP16

EXPERIMENTAL

IV Busulfan + 12 cGy FTBI + VP16 prior to allogeneic Bone Marrow Transplant

Drug: busulfan; Drug: cyclosporine; Drug: etoposide; Drug: mycophenolate mofetil; Procedure: allogeneic bone marrow transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: total-body irradiation

Interventions

busulfan DRUG

Busulfan, FTBI and VP16

cyclosporine DRUG

Busulfan, FTBI and VP16

etoposide DRUG

Busulfan, FTBI and VP16

mycophenolate mofetil DRUG

Busulfan, FTBI and VP16

allogeneic bone marrow transplantation PROCEDURE

Busulfan, FTBI and VP16

allogeneic hematopoietic stem cell transplantation PROCEDURE

Busulfan, FTBI and VP16

peripheral blood stem cell transplantation PROCEDURE

Busulfan, FTBI and VP16

total-body irradiation RADIATION

Busulfan, FTBI and VP16

Eligibility Criteria

• Age: 16 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: * Diagnosis of 1 of the following: * Acute myeloid leukemia (AML) * Failed remission induction therapy or in relapse beyond second remission * In first remission with poor risk cytogenetics (e.g., 11q abnormalities, -7, -5, complex abnormalities \[i.e., \> 3 abnormalities, 6;9 translocation and 3q abnormalities del (7q), del (5q), complex abnormalities ≥ abnormalities, 9q, 20q, 21q, 17q, t(9;21)\]) * Acute lymphoblastic leukemia (ALL) * Failed remission induction therapy or in relapse beyond second remission * Blastic phase chronic myelogenous leukemia * Refractory anemia with excess blasts * Refractory anemia with excess blasts in transformation * HLA -A, -B, -C, -DR identical sibling donor match available * No relapse after prior bone marrow transplantation PATIENT CHARACTERISTICS: * Cardiac ejection fraction ≥ 50% * Serum creatinine ≤ 1.2 times upper limit of normal (ULN) or creatinine clearance \> 80 mL/min * Bilirubin ≤ 1.5 times ULN * AST and ALT \< 5 times ULN * FEV\_1 ≥ 50% of predicted normal * DLCO ≥ 50% of predicted normal * No psychological or medical condition that would preclude allogeneic transplantation (in the opinion of the treating physician) * Not pregnant * Negative pregnancy test PRIOR CONCURRENT THERAPY: * See Disease Characteristics * At least 28 days since prior induction or reinduction therapy * Prior etoposide and busulfan allowed * No prior radiation therapy that would exclude total-body irradiation

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Congenital Abnormalities; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Blast Crisis; Anemia, Refractory, with Excess of Blasts

Interventions

Busulfan; Cyclosporine; Etoposide; Mycophenolic Acid; Peripheral Blood Stem Cell Transplantation; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Leukemia, Myeloid; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Anemia, Refractory; Anemia

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Glucosides; Glycosides; Carbohydrates; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Radiotherapy; Investigative Techniques

Results Point of Contact

• Title: Anthony Stein, MD, Clinical Professor
• Organization: Department of Hematology, City of Hope

astein@coh.org

626-537-5748

Study Officials

• Anthony S. Stein, MD

  City of Hope Comprehensive Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2007
• First Posted: September 24, 2007
• Study Start: February 29, 2000
• Primary Completion: April 12, 2010
• Study Completion: March 18, 2026
• Last Updated: June 3, 2025
• Results First Posted: October 10, 2023

Record last verified: 2025-05