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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

Information source: City of Hope Medical Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Leukemia

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

Phase: Phase 1/Phase 2

Status: Active, not recruiting

Sponsored by: City of Hope Medical Center

Official(s) and/or principal investigator(s):
Anthony S. Stein, MD, Study Chair, Affiliation: City of Hope Medical Center

Summary

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).

Clinical Details

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)

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

Primary outcome:

Maximum tolerated dose of intensity-modulated radiotherapy (Phase I)

Toxicity as assessed by NCI CTCAE v3.0 (Phase I)

Overall survival (Phase II)

Relapse-free survival (Phase II)

Event-free survival (Phase II)

Treatment-related mortality (Phase II)

Relapse rate (Phase II)

Fraction of patients experiencing 3-5 mucositis (Phase II)

Secondary outcome:

Infection (Phase II)

Acute and chronic graft-versus-host disease (Phase II)

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.

Eligibility

Minimum age: 7 Years. Maximum age: 55 Years. Gender(s): Both.

Criteria:

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%

Locations and Contacts

City of Hope Medical Center, Duarte, California 91010-3000, United States
Additional Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: February 2007
Last updated: March 2, 2015

Page last updated: August 23, 2015

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