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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00576979
First received: December 18, 2007
Last updated: January 29, 2014
Last verified: January 2014

December 18, 2007
January 29, 2014
February 2007
June 2015   (final data collection date for primary outcome measure)
  • Maximum tolerated dose of intensity-modulated radiotherapy (Phase I) [ Time Frame: 30 days post transplant ] [ Designated as safety issue: Yes ]
    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.
  • Toxicity as assessed by NCI CTCAE v3.0 (Phase I) [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    Toxicities observed at each dose level will be summarized in terms of type, severity, date of onset, duration, reversibility, and attribution. Tables will be created to summarize these toxicities and side effects by dose level.
  • Overall survival (Phase II) [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]
    Will be estimated using the product limit method of Kaplan-Meier and tested using the Log-Rank test. Confidence intervals will be estimated by calculating exact 95% confidence limits for a binomial parameter.
  • Relapse-free survival (Phase II) [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]
    Will be estimated using the product limit method of Kaplan-Meier and tested using the Log-Rank test. Confidence intervals will be estimated by calculating exact 95% confidence limits for a binomial parameter.
  • Event-free survival (Phase II) [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]
    Will be estimated using the product limit method of Kaplan-Meier and tested using the Log-Rank test. Confidence intervals will be estimated by calculating exact 95% confidence limits for a binomial parameter.
  • Treatment-related mortality (Phase II) [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]
    Will be estimated using the product limit method of Kaplan-Meier and tested using the Log-Rank test. Confidence intervals will be estimated by calculating exact 95% confidence limits for a binomial parameter.
  • Relapse rate (Phase II) [ Time Frame: 2 years post transplant ] [ Designated as safety issue: No ]
    Will be estimated using the product limit method of Kaplan-Meier and tested using the Log-Rank test. Confidence intervals will be estimated by calculating exact 95% confidence limits for a binomial parameter.
  • Fraction of patients experiencing 3-5 mucositis (Phase II) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Maximum tolerated dose of intensity-modulated radiotherapy (Phase I)
  • Toxicity (Phase I)
  • Overall survival (Phase II)
  • Relapse-free survival (Phase II)
  • Event-free survival (Phase II)
  • Treatment-related mortality (Phase II)
  • Relative risk (Phase II)
Complete list of historical versions of study NCT00576979 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Infection (Phase II)
  • Acute and chronic graft-versus-host disease (Phase II)
Not Provided
Not Provided
 
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
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)

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).

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.

Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Leukemia
  • Drug: cyclophosphamide
    Given IV
    Other Names:
    • CPM
    • CTX
    • Cytoxan
    • Endoxan
    • Endoxana
  • Drug: etoposide
    Given IV
    Other Names:
    • EPEG
    • VP-16
    • VP-16-213
  • 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: intensity-modulated radiation therapy
    Undergo IMRT
    Other Name: IMRT
  • Radiation: tomotherapy
    Undergo IMRT using helical tomotherapy
    Other Name: helical tomotherapy
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.
Interventions:
  • Drug: cyclophosphamide
  • Drug: etoposide
  • Procedure: allogeneic bone marrow transplantation
  • Procedure: allogeneic hematopoietic stem cell transplantation
  • Procedure: peripheral blood stem cell transplantation
  • Radiation: intensity-modulated radiation therapy
  • Radiation: tomotherapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
87
Not Provided
June 2015   (final data collection date for primary outcome measure)

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%
Both
7 Years to 55 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00576979
05021, P30CA033572, CHNMC-05021, CDR0000579141, NCI-2010-00427
Yes
City of Hope Medical Center
City of Hope Medical Center
National Cancer Institute (NCI)
Study Chair: Anthony S. Stein, MD City of Hope Medical Center
City of Hope Medical Center
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP