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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)


Phase 1/Phase 2
7 Years
55 Years
Open (Enrolling)
Both
Leukemia

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Trial Information

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)


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.


Inclusion Criteria:



- 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 an 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; 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 exam with a 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

- Bilirubin of less than or equal to 1.5

- Serum glutamic oxaloacetic transaminase (SGOT) less than 5 times the upper limit of
normal

- Serum glutamic pyruvic 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

- DONOR: Donors will be excluded if for psychological or medical reasons they are
unable to tolerate the procedure

- DONOR: Donor should be able to donate peripheral blood stem cells or bone marrow

Exclusion Criteria:

- 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%

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 radiotherapy (Phase I)

Outcome Description:

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.

Outcome Time Frame:

30 days post transplant

Safety Issue:

Yes

Principal Investigator

Anthony S. Stein, MD

Investigator Role:

Study Chair

Investigator Affiliation:

City of Hope Medical Center

Authority:

United States: Institutional Review Board

Study ID:

05021

NCT ID:

NCT00576979

Start Date:

February 2007

Completion Date:

Related Keywords:

  • Leukemia
  • recurrent adult acute lymphoblastic leukemia
  • recurrent childhood acute lymphoblastic leukemia
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid

Name

Location

City of Hope Medical CenterDuarte, California  91010