Adult Acute Myeloid Leukemia in RemissionPhase 1/2NCT00540995

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

A Phase 1/2 study testing busulfan, etoposide and intensity-modulated radiation therapy in people with Adult Acute Myeloid Leukemia in Remission and Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, run by City of Hope Medical Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 6 to 55 years
Conditions the study is for: Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q)
What is being tested?: busulfan, etoposide and intensity-modulated radiation therapy
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 25 participants
Where: 1 siteUnited States
Study dates: 11 Jun 2007to 9 Aug 2011
Phase: Phase 1/2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 6 to 55 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

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

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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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

City of Hope
Duarte, California, 91010

Other trials in United States

About this study

Official title: 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

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.

Read the detailed description

OBJECTIVES:

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)
Being tested: busulfan, etoposide, intensity-modulated radiation therapy, allogeneic hematopoietic stem cell transplantation, allogeneic bone marrow transplantation
Medical subject headings: Congenital Abnormalities, Blast Crisis, Leukemia, Myeloid, Acute, Anemia, Refractory, with Excess of Blasts

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

busulfanDrug
Also called BSF, BU, Misulfan, Mitosan
Given IV
etoposideDrug
Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, epipodophyllotoxin, VePesid
Given IV
intensity-modulated radiation therapyRadiation
Also called IMRT
Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses
allogeneic hematopoietic stem cell transplantationProcedure or surgery
Stem cell transplantation occurs on Day 0 after High Dose Therapy
allogeneic bone marrow transplantationProcedure or surgery
Also called bone marrow therapy, allogeneic, bone marrow therapy, allogenic, transplantation, allogeneic bone marrow, transplantation, allogenic bone marrow
Stem cell transplantation occurs on Day 0 after High Dose Therapy
peripheral blood stem cell transplantationProcedure or surgery
Also called PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Stem cell transplantation occurs on Day 0 after High Dose Therapy
tomotherapyRadiation
Also called helical tomotherapy
Initially 150 cGy X 8 doses with gradual dose escalation to 200 cGy X 10 doses

Study groups in NCT00540995
Study group	Role	What they receive
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. Receives: 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. Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: from initial treatment date to Day 30 post-transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Jun 20079 Aug 2011

First posted8 Oct 2007 (estimated)
Study start11 Jun 2007
Primary completion17 May 2011
Study completion9 Aug 2011

Why it stopped: Unable to safely escalate to TMLI doses that were hypothesized to be effective and less toxic than FTBI. Likely due to the giving of Busulfan prior to radiation delivery. Therefore, the study was abandoned and no further patients were accrued.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Adult Acute Myeloid Leukemia in RemissionStudies of the same condition, open and under way.
More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 25 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00540995
Sponsor's protocol ID: 05013
Other IDs: NCI-2010-00354, CDR0000567452
Status last verified: Nov 2023
First submitted: 5 Oct 2007
Last updated: 30 Nov 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No: Terminated study

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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