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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

Primary Purpose

Leukemia

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
cyclophosphamide
etoposide
allogeneic bone marrow transplantation
allogeneic hematopoietic stem cell transplantation
peripheral blood stem cell transplantation
intensity-modulated radiation therapy
tomotherapy
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring recurrent adult acute lymphoblastic leukemia, recurrent childhood acute lymphoblastic leukemia

Eligibility Criteria

7 Years - 55 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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 a human leukocyte antigen (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; a single allele mismatch at A, B, C, DR, or DQ and a KIR mismatch at C will be allowed; 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 evaluation with an 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
  • A bilirubin of less than or equal to 1.5
  • Serum glutamic oxaloacetic transaminase (SGOT) less than 5 times the upper limit of normal
  • Serum glutamate pyruvate 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

  • Donors will be excluded if for psychological or medical reasons they are unable to tolerate the procedure
  • 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%

Sites / Locations

  • City of Hope Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Level 1: 1200cGy

Level 2: 1350cGy

Level 3: 1500cGy limited dose to ribs, sternum, liver, brain 1200cGy

Level 4: 1500cGy limited dose to liver, brain 1200cGy

Level 5: 1600cGy limited dose to liver, porta-hepatic, brain 1200cGy

Level 6: 1700cGy limited dose to liver, porta-hepatic, brain 1200cGy

Level 7: 1800cGy limited dose to liver, porta-hepatic, brain 1200cGy

Level 8: 1900cGy limited dose to liver, porta-hepatic, brain 1200cGy

Level 9: 2000cGy limited dose to liver, porta-hepatic, brain 1200cGy

Arm Description

150cGy BID x Days 1-4. Total dose 1200cGy.

150cGy BID Day 1-4 then 150 cGy QD Day 5. Total dose 1350cGy.

150cGy BID Day 1-5. Total dose 1500Gy.

150cGy BID Day 1-5. Total dose 1500Gy.

160cGy BID Day 1-5. Total dose 1600Gy.

170cGy BID Day 1-5. Total dose 1700Gy.

180cGy BID Day 1-5. Total dose 1800Gy.

190cGy BID Day 1-5. Total dose 1900Gy.

200cGy BID Day 1-5. Total dose 2000Gy.

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose of Intensity-modulated Radiotherapy (Phase I)
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.

Secondary Outcome Measures

Full Information

First Posted
December 18, 2007
Last Updated
July 14, 2023
Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00576979
Brief Title
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
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 Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 4, 2008 (Actual)
Primary Completion Date
May 30, 2016 (Actual)
Study Completion Date
December 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia
Keywords
recurrent adult acute lymphoblastic leukemia, recurrent childhood acute lymphoblastic leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
51 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Level 1: 1200cGy
Arm Type
Experimental
Arm Description
150cGy BID x Days 1-4. Total dose 1200cGy.
Arm Title
Level 2: 1350cGy
Arm Type
Experimental
Arm Description
150cGy BID Day 1-4 then 150 cGy QD Day 5. Total dose 1350cGy.
Arm Title
Level 3: 1500cGy limited dose to ribs, sternum, liver, brain 1200cGy
Arm Type
Experimental
Arm Description
150cGy BID Day 1-5. Total dose 1500Gy.
Arm Title
Level 4: 1500cGy limited dose to liver, brain 1200cGy
Arm Type
Experimental
Arm Description
150cGy BID Day 1-5. Total dose 1500Gy.
Arm Title
Level 5: 1600cGy limited dose to liver, porta-hepatic, brain 1200cGy
Arm Type
Experimental
Arm Description
160cGy BID Day 1-5. Total dose 1600Gy.
Arm Title
Level 6: 1700cGy limited dose to liver, porta-hepatic, brain 1200cGy
Arm Type
Experimental
Arm Description
170cGy BID Day 1-5. Total dose 1700Gy.
Arm Title
Level 7: 1800cGy limited dose to liver, porta-hepatic, brain 1200cGy
Arm Type
Experimental
Arm Description
180cGy BID Day 1-5. Total dose 1800Gy.
Arm Title
Level 8: 1900cGy limited dose to liver, porta-hepatic, brain 1200cGy
Arm Type
Experimental
Arm Description
190cGy BID Day 1-5. Total dose 1900Gy.
Arm Title
Level 9: 2000cGy limited dose to liver, porta-hepatic, brain 1200cGy
Arm Type
Experimental
Arm Description
200cGy BID Day 1-5. Total dose 2000Gy.
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
CPM, CTX, Cytoxan, Endoxan, Endoxana
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
etoposide
Other Intervention Name(s)
EPEG, VP-16, VP-16-213
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
allogeneic bone marrow transplantation
Intervention Description
Occurs approximately 48 hours after completion of cyclophosphamide
Intervention Type
Procedure
Intervention Name(s)
allogeneic hematopoietic stem cell transplantation
Intervention Description
Occurs approximately 48 hours after completion of cyclophosphamide
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Intervention Description
Occurs approximately 48 hours after completion of cyclophosphamide
Intervention Type
Radiation
Intervention Name(s)
intensity-modulated radiation therapy
Other Intervention Name(s)
IMRT
Intervention Description
Undergo IMRT
Intervention Type
Radiation
Intervention Name(s)
tomotherapy
Other Intervention Name(s)
helical tomotherapy
Intervention Description
Undergo IMRT using helical tomotherapy
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose of Intensity-modulated Radiotherapy (Phase I)
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.
Time Frame
30 days post transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
7 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility 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 a human leukocyte antigen (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; a single allele mismatch at A, B, C, DR, or DQ and a KIR mismatch at C will be allowed; 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 evaluation with an 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 A bilirubin of less than or equal to 1.5 Serum glutamic oxaloacetic transaminase (SGOT) less than 5 times the upper limit of normal Serum glutamate pyruvate 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 Donors will be excluded if for psychological or medical reasons they are unable to tolerate the procedure 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%
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anthony S. Stein, MD
Organizational Affiliation
City of Hope Medical Center
Official's Role
Study Chair
Facility Information:
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010-3000
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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