LeukemiaPhase 1/2NCT00576979

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

A Phase 1/2 study testing cyclophosphamide, etoposide and allogeneic bone marrow transplantation in people with Leukemia, run by City of Hope Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 7 to 55 years
Conditions the study is for: Leukemia
What is being tested?: cyclophosphamide, etoposide and allogeneic bone marrow transplantation
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 51 participants
Where: 1 siteUnited States
Study dates: 4 Mar 2008to 7 Jan 2026
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 7 to 55 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

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

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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

Who cannot join

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%

Trial locations and contacts

1 site in 1 country.

United States1 site

City of Hope Medical Center
Duarte, California, 91010-3000

Other trials in United States

About this study

Official title: 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)

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).

Read the detailed description

OBJECTIVES: I. To establish the maximum tolerated dose [MTD] of large field image-guided IMRT, using helical tomotherapy when given in combination with intravenous cyclophosphamide and VP-16 as a preparative regimen for allogeneic hematopoietic stem cell transplantation (HSCT) from an human leukocyte antigen (HLA)-identical sibling or unrelated donor in patients with ALL or AML with induction failure or in relapse. (Phase I) II. To describe the toxicity at each dose level standard. (Phase I) III. To collect data on the radiation dose to normal organs and bone marrow using tomotherapy targeted total-body irradiation (TBI). (Phase I) IV. To estimate the overall survival probability, disease free survival probability and relapse rate associated with this 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 radiation. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of intensity-modulated radiation therapy (IMRT) followed by a phase II study.

PREPARATIVE REGIMEN: Patients undergo IMRT using helical tomotherapy once or twice daily on days -10 to -6 or -10 to -7. Patients also receive etoposide intravenously (IV) on day -6 or -5 and cyclophosphamide IV on day -4 or -3.

TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell or bone marrow transplantation on day -1 or day 0. After completion of study treatment, patients are followed up periodically for up to 2 years.

Conditions: Leukemia
Being tested: cyclophosphamide, etoposide, allogeneic bone marrow transplantation, allogeneic hematopoietic stem cell transplantation, peripheral blood stem cell transplantation
Keywords: recurrent adult acute lymphoblastic leukemia, recurrent childhood acute lymphoblastic leukemia
Medical subject headings: Leukemia, Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

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

cyclophosphamideDrug
Also called CPM, CTX, Cytoxan, Endoxan
Given IV
etoposideDrug
Also called EPEG, VP-16, VP-16-213
Given IV
allogeneic bone marrow transplantationProcedure or surgery
Occurs approximately 48 hours after completion of cyclophosphamide
allogeneic hematopoietic stem cell transplantationProcedure or surgery
Occurs approximately 48 hours after completion of cyclophosphamide
peripheral blood stem cell transplantationProcedure or surgery
Occurs approximately 48 hours after completion of cyclophosphamide
intensity-modulated radiation therapyRadiation
Also called IMRT
Undergo IMRT
tomotherapyRadiation
Also called helical tomotherapy
Undergo IMRT using helical tomotherapy

Study groups in NCT00576979
Study group	Role	What they receive
Level 1: 1200cGy	Experimental	150cGy BID x Days 1-4. Total dose 1200cGy. Receives: Drug: cyclophosphamide; Drug: etoposide; Procedure: allogeneic bone marrow transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: intensity-modulated radiation therapy; Radiation: tomotherapy
Level 2: 1350cGy	Experimental	150cGy BID Day 1-4 then 150 cGy QD Day 5. Total dose 1350cGy. Receives: Drug: cyclophosphamide; Drug: etoposide; Procedure: allogeneic bone marrow transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: intensity-modulated radiation therapy; Radiation: tomotherapy
Level 3: 1500cGy limited dose to ribs, sternum, liver, brain 1200cGy	Experimental	150cGy BID Day 1-5. Total dose 1500Gy. Receives: Drug: cyclophosphamide; Drug: etoposide; Procedure: allogeneic bone marrow transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: intensity-modulated radiation therapy; Radiation: tomotherapy
Level 4: 1500cGy limited dose to liver, brain 1200cGy	Experimental	150cGy BID Day 1-5. Total dose 1500Gy. Receives: Drug: cyclophosphamide; Drug: etoposide; Procedure: allogeneic bone marrow transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: intensity-modulated radiation therapy; Radiation: tomotherapy
Level 5: 1600cGy limited dose to liver, porta-hepatic, brain 1200cGy	Experimental	160cGy BID Day 1-5. Total dose 1600Gy. Receives: Drug: cyclophosphamide; Drug: etoposide; Procedure: allogeneic bone marrow transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: intensity-modulated radiation therapy; Radiation: tomotherapy
Level 6: 1700cGy limited dose to liver, porta-hepatic, brain 1200cGy	Experimental	170cGy BID Day 1-5. Total dose 1700Gy. Receives: Drug: cyclophosphamide; Drug: etoposide; Procedure: allogeneic bone marrow transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: intensity-modulated radiation therapy; Radiation: tomotherapy
Level 7: 1800cGy limited dose to liver, porta-hepatic, brain 1200cGy	Experimental	180cGy BID Day 1-5. Total dose 1800Gy. Receives: Drug: cyclophosphamide; Drug: etoposide; Procedure: allogeneic bone marrow transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: intensity-modulated radiation therapy; Radiation: tomotherapy
Level 8: 1900cGy limited dose to liver, porta-hepatic, brain 1200cGy	Experimental	190cGy BID Day 1-5. Total dose 1900Gy. Receives: Drug: cyclophosphamide; Drug: etoposide; Procedure: allogeneic bone marrow transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: intensity-modulated radiation therapy; Radiation: tomotherapy
Level 9: 2000cGy limited dose to liver, porta-hepatic, brain 1200cGy	Experimental	200cGy BID Day 1-5. Total dose 2000Gy. Receives: Drug: cyclophosphamide; Drug: etoposide; Procedure: allogeneic bone marrow transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: intensity-modulated radiation therapy; Radiation: tomotherapy

What is being measured

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

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.
Measured: 30 days post transplant

Timeline

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

4 Mar 20087 Jan 2026

First posted19 Dec 2007 (estimated)
Study start4 Mar 2008
Primary completion30 May 2016
Study completion7 Jan 2026

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 LeukemiaStudies 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: 51 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00576979
Sponsor's protocol ID: 05021
Other IDs: CHNMC-05021, CDR0000579141, NCI-2010-00427, R01CA154491
Status last verified: Mar 2026
First submitted: 18 Dec 2007
Last updated: 24 Mar 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

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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