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: July 17, 2014
Last verified: July 2014
  Purpose

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).


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: intensity-modulated radiation therapy
Radiation: tomotherapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
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:


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 ]
    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 ]

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: 87
Study Start Date: February 2007
Estimated Primary Completion Date: June 2015 (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
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

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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010-3000
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Study Chair: Anthony S. Stein, MD City of Hope Medical Center
  More Information

Additional Information:
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: July 17, 2014
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
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 27, 2014