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

NCT00540995 | Terminated Phase 1 Results DMC

• 3 other identifiers: 05013NCI-2010-00354CDR0000567452
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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.

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

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Intensity-modulated Radiation Therapy (Phase I)

  The highest dose tested in which fewer than 33% of patients experienced DLT attributable to the study treatment when at least six patients were treated at the dose and are evaluable for toxicity. The MDT is one dose level below the DLT level. At least six patients will be treated at the MTD.

  from initial treatment date to Day 30 post-transplant

Study Arms (2)

Arm I: 1200cGy

EXPERIMENTAL

1200cGy = 150cGy x 8 doses: 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.

Drug: busulfan; Drug: etoposide; Radiation: intensity-modulated radiation therapy; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: allogeneic bone marrow transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: tomotherapy

Arm II: 1350cGy

EXPERIMENTAL

1350cGy = 150cGy x 9 doses: 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.

Drug: busulfan; Drug: etoposide; Radiation: intensity-modulated radiation therapy; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: allogeneic bone marrow transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: tomotherapy

Interventions

busulfan DRUG

Given IV

Also known as: BSF, BU, Misulfan, Mitosan, Myeloleukon, Myelosan

Arm I: 1200cGy; Arm II: 1350cGy

etoposide DRUG

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, epipodophyllotoxin, VePesid, VP-16, VP-16-213

Arm I: 1200cGy; Arm II: 1350cGy

intensity-modulated radiation therapy RADIATION

Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses

Also known as: IMRT

Arm I: 1200cGy; Arm II: 1350cGy

allogeneic hematopoietic stem cell transplantation PROCEDURE

Stem cell transplantation occurs on Day 0 after High Dose Therapy

Arm I: 1200cGy; Arm II: 1350cGy

allogeneic bone marrow transplantation PROCEDURE

Stem cell transplantation occurs on Day 0 after High Dose Therapy

Also known as: bone marrow therapy, allogeneic, bone marrow therapy, allogenic, transplantation, allogeneic bone marrow, transplantation, allogenic bone marrow

Arm I: 1200cGy; Arm II: 1350cGy

peripheral blood stem cell transplantation PROCEDURE

Stem cell transplantation occurs on Day 0 after High Dose Therapy

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

Arm I: 1200cGy; Arm II: 1350cGy

tomotherapy RADIATION

Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses

Also known as: helical tomotherapy

Arm I: 1200cGy; Arm II: 1350cGy

Eligibility Criteria

• Age: 6 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients with the following diagnoses are eligible for this study: Advanced myeloid malignancy with a disease status of more than second remission, induction failure, or relapse; Chronic myeloid leukemia in blast crisis; Myelodysplasia, specifically refractory anemia with excess blasts (RAEB)
• All candidates for this study must have a 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 or minor mismatches as per BMT SOP that allows Tacrolimus and Sirolimus to be given for GVH prophylaxis; 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)
• Prior therapy with VP-16, busulfan, hydrea and gleevec are allowed
• A cardiac evaluation with electrocardiogram and MUGA or echocardiogram is required for all patients; patients must have an ejection fracture of greater than or equal to 50%
• 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; patients should also have an SGOT and SGPT less than 5 times the upper limit of normal
• Pulmonary function tests including DLCO will be performed; FEV1 and DLCO should be greater than 50% of predicted normal value
• Time from the end of last induction or reinduction attempt should be greater than or equal to 21 days
• A signed (IRB approved) informed consent document is required; the patient, donor family member, and transplant team (physician, nurse, and social worker) meet together at least once prior to starting the transplant procedure to review all pertinent risk/benefit information as part of the consenting process; alternative treatment modalities are also discussed at this meeting

You may not qualify if:

• Prior radiation therapy/exposure that prevents patient from receiving IMRT (Determination will be made by the Radiation Oncologist)
• Patients who have previously undergone a blood/marrow transplant and now have relapsed disease
• Patients with a psychological or medical condition that the treating physician deems unacceptable to proceed to allogeneic bone marrow transplant
• Pregnancy
• EKG showing ischemic changes or abnormal rhythm and echocardiogram showing ejection fraction \< 50 % or abnormal wall motion

Sponsors & Collaborators

• City of Hope Medical Center: lead

Study Sites (1)

City of Hope

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Congenital Abnormalities; Blast Crisis; Leukemia, Myeloid, Acute; Anemia, Refractory, with Excess of Blasts

Interventions

Busulfan; Etoposide; Podophyllotoxin; Radiotherapy, Intensity-Modulated; Transplantation; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Lignans; Benzyl Compounds; Benzene Derivatives; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Surgical Procedures, Operative; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy

Results Point of Contact

• Title: Dr. Anthony Stein
• Organization: City of Hope Medical Center

626-359-8111

Study Officials

• Anthony Stein

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: October 5, 2007
• First Posted: October 8, 2007
• Study Start: June 11, 2007
• Primary Completion: May 17, 2011
• Study Completion: August 9, 2011
• Last Updated: November 30, 2023
• Results First Posted: November 22, 2021

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)