Intensity-Modulated Radiation Therapy, Etoposide, and Cyclophosphamide Followed By Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia - Full Text View

Sponsors and Collaborators:	Beckman Research Institute National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00576979

Purpose

RATIONALE: Giving intensity-modulated radiation therapy and chemotherapy 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 chemotherapy before transplant may stop this from happening.

PURPOSE: This phase I/II clinical trial is studying the side effects and best dose of intensity-modulated radiation therapy 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.

Condition	Intervention	Phase
Leukemia	Drug: cyclophosphamide Drug: etoposide Procedure: allogeneic bone marrow transplantation Procedure: allogeneic hematopoietic stem cell transplantation Procedure: image-guided radiation therapy Procedure: intensity-modulated radiation therapy Procedure: peripheral blood stem cell transplantation Procedure: tomotherapy	Phase I Phase II

MedlinePlus related topics: Bone Marrow Transplantation Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

Drug Information available for: Cyclophosphamide Etoposide Etoposide phosphate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
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 (VP-16) and Cytoxan as a Preparative Regimen for Allogeneic Hematopoietic Stem Cell (HSC) Transplantation for Patients With Poor Risk Acute Lymphocytic Leukemia (ALL)

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Maximum tolerated dose of intensity-modulated radiotherapy (Phase I) [ Designated as safety issue: Yes ]
Toxicity (Phase I) [ Designated as safety issue: Yes ]
Overall survival (Phase II) [ Designated as safety issue: No ]
Relapse-free survival (Phase II) [ Designated as safety issue: No ]
Event-free survival (Phase II) [ Designated as safety issue: No ]
Treatment-related mortality (Phase II) [ Designated as safety issue: No ]
Relative risk (Phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Infection (Phase II) [ Designated as safety issue: No ]
Acute and chronic graft-versus-host disease (Phase II) [ Designated as safety issue: No ]

Estimated Enrollment:	75
Study Start Date:	February 2007
Estimated Primary Completion Date:	October 2012 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

To establish the maximum tolerated dose of large field image-guided intensity-modulated radiotherapy using helical tomotherapy when given in combination with etoposide and cyclophosphamide followed by HLA-matched allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory acute lymphoblastic leukemia. (Phase I)
To describe the toxicity at each dose level. (Phase I)
To collect data on the radiation dose to normal organs and bone marrow using tomotherapy targeted total-body irradiation. (Phase I)
To estimate the overall survival probability, disease-free survival probability, and relapse rate associated with this regimen. (Phase II)
To characterize the treatment-related mortality and toxicity profile (early/late) associated with this regimen. (Phase II)
To descriptively compare the outcomes of patients treated on this study to a comparable patient population conditioned with whole-body radiotherapy. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of intensity-modulated radiotherapy (IMRT) using helical tomotherapy, followed by a phase II study. Patients are stratified by age (≥ 18 years of age but ≤ 50 years of age vs 6-17 years of age).

Phase I:
- Preparative regimen: Patients undergo IMRT using helical tomotherapy once or twice daily on days -9 to -6 or -9 to -5 (depending on dose). Patients also receive etoposide IV on day -5 or -4 and cyclophosphamide IV on day -3 or -2.

Cohorts of patients receive escalating doses of IMRT until the maximum tolerated dose (MTD) is determined .

Allogeneic hematopoietic stem cell transplantation: Patients undergo allogeneic peripheral blood stem cell or bone marrow transplantation on day 0.
- Phase II: Patients receive IMRT at the MTD determined in phase I and undergo treatment in phase I.

After completion of study treatment, patients are followed periodically for up to 2 years.

Eligibility

Ages Eligible for Study:	6 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of acute lymphoblastic leukemia
- Not in first or second remission (i.e., failed remission induction therapy, in relapse, or beyond second remission)
HLA-matched donor available who is willing to donate bone marrow or peripheral blood stem cells AND meets 1 of the following criteria:
- HLA-A, -B, -C and -DR matched identical sibling donor
- 10/10 allele matched unrelated donor

PATIENT CHARACTERISTICS:

Creatinine ≤ 1.2 mg/dL OR creatinine clearance > 80 mL/min
Bilirubin ≤ 1.5 mg/dL
AST and ALT < 5 times upper limit of normal
FEV_1 > 50% of predicted
DLCO > 50% of predicted
Ejection fraction ≥ 50% by MUGA or ECHO
No abnormal wall motion by MUGA or ECHO
No ischemic changes or abnormal rhythm by EKG
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No psychological or medical condition that would preclude allogeneic stem cell transplantation

PRIOR CONCURRENT THERAPY:

Prior therapy with etoposide and cyclophosphamide allowed
At least 21 days since prior induction or reinduction therapy
No prior radiation therapy that would exclude the use of total-body irradiation
No prior bone marrow transplantation that resulted in disease relapse

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00576979

Locations

United States, California
City of Hope Comprehensive Cancer Center	Recruiting
Duarte, California, United States, 91010-3000
Contact: Clinical Trials Office - City of Hope Comprehensive Cancer Cen 800-826-4673 becomingapatient@coh.org

Sponsors and Collaborators

Beckman Research Institute

National Cancer Institute (NCI)

Investigators

Study Chair:

Anthony S. Stein, MD

Beckman Research Institute

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Responsible Party:	City of Hope Comprehensive Cancer Center ( Anthony S. Stein )
Study ID Numbers:	CDR0000579141, CHNMC-05021
Study First Received:	December 18, 2007
Last Updated:	December 9, 2008
ClinicalTrials.gov Identifier:	NCT00576979
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

recurrent adult acute lymphoblastic leukemia
recurrent childhood acute lymphoblastic leukemia

Study placed in the following topic categories:

Lymphatic Diseases
Leukemia
Leukemia, Lymphoid
Immunoproliferative Disorders
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Cyclophosphamide

Lymphoproliferative Disorders
Etoposide phosphate
Etoposide
Lymphoma
Recurrence
Acute lymphoblastic leukemia, adult

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Immune System Diseases
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Immunosuppressive Agents
Pharmacologic Actions

Neoplasms
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009