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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


Phase 1/Phase 2
6 Years
55 Years
Open (Enrolling)
Both
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

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Trial Information

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


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.

Inclusion Criteria


Inclusion

- 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

Exclusion

- 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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of intensity-modulated radiation therapy (Phase I)

Outcome Time Frame:

18 months post therapy

Safety Issue:

Yes

Principal Investigator

Anthony Stein

Investigator Role:

Principal Investigator

Investigator Affiliation:

Beckman Research Institute

Authority:

United States: Institutional Review Board

Study ID:

05013

NCT ID:

NCT00540995

Start Date:

September 2006

Completion Date:

Related Keywords:

  • 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
  • Congenital Abnormalities
  • Anemia
  • Anemia, Refractory
  • Anemia, Refractory, with Excess of Blasts
  • Blast Crisis
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Myelodysplastic Syndromes
  • Preleukemia

Name

Location

City of HopeDuarte, California  91010