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 - Full Text View

Purpose

RATIONALE: Giving intensity-modulated radiation therapy 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 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 (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 or acute myeloid leukemia (AML).

Condition	Intervention	Phase
Leukemia	Drug: cyclophosphamide Drug: etoposide Procedure: allogeneic bone marrow transplantation Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Radiation: image-guided radiation therapy Radiation: intensity-modulated radiation therapy Radiation: tomotherapy	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: 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 (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)

Resource links provided by NLM:

Genetics Home Reference related topics: familial acute myeloid leukemia with mutated CEBPA

MedlinePlus related topics: Acute Myeloid Leukemia Bone Marrow Transplantation Chronic Lymphocytic Leukemia Leukemia

Drug Information available for: Cyclophosphamide Etoposide Etoposide phosphate

U.S. FDA Resources

Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:

Maximum tolerated dose of intensity-modulated radiotherapy (Phase I) [ Time Frame: 30 days post transplant ] [ Designated as safety issue: Yes ]
Toxicity as assessed by NCI CTCAE v3.0 (Phase I) [ Time Frame: 100 days post transplant ] [ Designated as safety issue: Yes ]
Overall survival (Phase II) [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]
Relapse-free survival (Phase II) [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]
Event-free survival (Phase II) [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]
Treatment-related mortality (Phase II) [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]
Relative risk (Phase II) [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Infection (Phase II) [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]
Acute and chronic graft-versus-host disease (Phase II) [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]

Estimated Enrollment:	75
Study Start Date:	February 2007
Estimated Primary Completion Date:	June 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Treatment (radiation therapy, chemotherapy, transplant) 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 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.	Drug: cyclophosphamide 100 mg/kg (ideal body weight)on day -3 from transplant or day -4 when IMRT is given over 4 days. Drug: etoposide 60 mg/kg (calculated on adjusted ideal body weight) on day -5 from transplant or day -6 when IMRT is given over 4 days. Procedure: allogeneic bone marrow transplantation Occurs approximately 48 hours after completion of cyclophosphamide Procedure: allogeneic hematopoietic stem cell transplantation Occurs approximately 48 hours after completion of cyclophosphamide Procedure: peripheral blood stem cell transplantation Occurs approximately 48 hours after completion of cyclophosphamide Radiation: image-guided radiation therapy Day -10 through Day -6 from transplant depending on dosing. Dose escalation schedule as follows: 150cGy x 8 doses, 150cGy x 9 doses, 150 cGy x 10 doses, 175 cGy x 10 doses and 200cGy x 10 doses. Radiation: intensity-modulated radiation therapy Day -10 through Day -6 from transplant depending on dosing. Dose escalation schedule as follows: 150cGy x 8 doses, 150cGy x 9 doses, 150 cGy x 10 doses, 175 cGy x 10 doses and 200cGy x 10 doses. Radiation: tomotherapy Day -10 through Day -6 from transplant depending on dosing. Dose escalation schedule as follows: 150cGy x 8 doses, 150cGy x 9 doses, 150 cGy x 10 doses, 175 cGy x 10 doses and 200cGy x 10 doses.

Arms

Assigned Interventions

Experimental: Treatment (radiation therapy, chemotherapy, transplant)

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 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.

Drug: cyclophosphamide

100 mg/kg (ideal body weight)on day -3 from transplant or day -4 when IMRT is given over 4 days.

Drug: etoposide

60 mg/kg (calculated on adjusted ideal body weight) on day -5 from transplant or day -6 when IMRT is given over 4 days.

Procedure: allogeneic bone marrow transplantation

Occurs approximately 48 hours after completion of cyclophosphamide

Procedure: allogeneic hematopoietic stem cell transplantation

Occurs approximately 48 hours after completion of cyclophosphamide

Procedure: peripheral blood stem cell transplantation

Occurs approximately 48 hours after completion of cyclophosphamide

Radiation: image-guided radiation therapy

Day -10 through Day -6 from transplant depending on dosing. Dose escalation schedule as follows: 150cGy x 8 doses, 150cGy x 9 doses, 150 cGy x 10 doses, 175 cGy x 10 doses and 200cGy x 10 doses.

Radiation: intensity-modulated radiation therapy

Day -10 through Day -6 from transplant depending on dosing. Dose escalation schedule as follows: 150cGy x 8 doses, 150cGy x 9 doses, 150 cGy x 10 doses, 175 cGy x 10 doses and 200cGy x 10 doses.

Radiation: tomotherapy

Day -10 through Day -6 from transplant depending on dosing. Dose escalation schedule as follows: 150cGy x 8 doses, 150cGy x 9 doses, 150 cGy x 10 doses, 175 cGy x 10 doses and 200cGy x 10 doses.

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 as a preparative regimen followed by HLA-matched allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory acute lymphoblastic leukemia or acute myelogenous 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 ≤ 55 years of age vs 6-17 years of age).

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

Ages Eligible for Study:	7 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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%

Contacts and Locations

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

Locations

United States, California
City of Hope Medical Center	Recruiting
Duarte, California, United States, 91010-3000
Contact: Joel Conrad 800-826-4673

Sponsors and Collaborators

City of Hope Medical Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Anthony S. Stein, MD

City of Hope Medical Center

More Information

Additional Information:

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

No publications provided

Responsible Party:	City of Hope Medical Center
ClinicalTrials.gov Identifier:	NCT00576979 History of Changes
Other Study ID Numbers:	05021, P30CA033572, CHNMC-05021, CDR0000579141, NCI-2010-00427
Study First Received:	December 18, 2007
Last Updated:	January 7, 2013
Health Authority:	United States: Institutional Review Board

Keywords provided by City of Hope Medical Center:

recurrent adult acute lymphoblastic leukemia
recurrent childhood acute lymphoblastic leukemia

Additional relevant MeSH terms:

Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Etoposide phosphate

Etoposide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on May 23, 2013