Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00054327
First received: February 5, 2003
Last updated: June 19, 2013
Last verified: June 2013

February 5, 2003
June 19, 2013
November 2000
September 2011   (final data collection date for primary outcome measure)
Rates of Durable Engraftment [ Time Frame: at day 42 ] [ Designated as safety issue: No ]
Number of days that patients take to reach engraftment defined as time to hematologic engraftment will be defined as ANC >500/µl and platelets >20K/µl without transfusion support.
Not Provided
Complete list of historical versions of study NCT00054327 on ClinicalTrials.gov Archive Site
  • Graft-versus-host Disease (GVHD) [ Time Frame: at 100 days post transplant ] [ Designated as safety issue: No ]
    Number of patients that develop acute graft-versus-host disease by grades 0-4. Grade O is no development of GVHD. Grade 1-4 is increase severity of skin, liver and gut involvement with 1 being least severe and 4 being most severe.
  • Incidence of Recurrent Disease [ Time Frame: at day 100 post transplant ] [ Designated as safety issue: No ]
    Number of patients that have disease recurrence.
  • Toxicity as Measured by CTC v2.0 [ Time Frame: at 100 days post transplant ] [ Designated as safety issue: Yes ]
    Number of patients that experience grade 3 or above toxicity. See serious adverse event list for toxicities.
Not Provided
Not Provided
Not Provided
 
Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer
Hematopoietic Stem Cell Transplantation Using Bone Marrow Or Peripheral Blood Stem Cells From Matched, Unrelated, Volunteer Donors

RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral stem cell transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the stem cells from a related donor, that do not exactly match the patient's blood, are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

PURPOSE: This phase II trial is studying how well giving chemotherapy with or without radiation therapy followed by donor stem cell transplant works in treating patients with hematologic cancer.

OBJECTIVES:

  • Determine a standard approach to hematopoietic stem cell transplantation with matched unrelated donors in patients with hematologic malignancies.
  • Determine the toxicity of this regimen in these patients.
  • Determine the relapse rate and survival rate in patients treated with this regimen.
  • Correlate incidence and severity of graft-versus-host disease with relapse and survival in patients treated with this regimen.

OUTLINE: Patients receive 1 of the following preparative regimens:

  • Regimen A: Patients receive cytarabine IV over 1 hour twice daily on days -9 to -7 and cyclophosphamide IV over 2 hours on days -6 and -5. Patients also undergo total body irradiation (TBI) twice daily on days -4 to -1.
  • Regimen B-1: Patients receive cyclophosphamide IV and TBI as in regimen A.
  • Regimen B-2: Patients receive cyclophosphamide IV over 2 hours on days -5 and -4. Patients also undergo TBI twice daily on days -3 to -1.
  • Regimen B-3: Patients receive TBI on days -7 to -5. Patients receive cyclophosphamide IV over on days -4 to -3.
  • Regimen C: Patients receive oral busulfan 4 times daily on days -8 to -5 and cyclophosphamide IV over 2 hours on days -4 to -2.
  • Regimen D: Patients receive TBI on days -6 to -4. Patients receive etoposide infusion on day -3.

All patients undergo stem cell transplantation from a matched, unrelated donor on day 0.

Patients are followed weekly for 100 days, at 6 months, and then every 6 months for 2.5 years.

PROJECTED ACCRUAL: 50

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Leukemia
  • Lymphoma
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Diseases
  • Drug: busulfan
    Given orally 1mg/kg/dose (or 40mg/m2/dose for young children)
    Other Name: Myleran
  • Drug: cyclophosphamide
    Given IV
    Other Names:
    • cytoxan
    • CTX
    • CPM
  • Drug: cytarabine
    Given IV
    Other Names:
    • Cytosine Arabinoside
    • Cytosar-U
    • Ara-C
    • Arabinosyl
  • Radiation: radiation therapy
    Patients undergo total body irradiation
    Other Name: Total body irradiation
  • Drug: Etoposide
    infusion
    Other Names:
    • VP-16
    • VePesid®
    • VP-16-213
    • EPEG
    • epipodophyllotoixn
  • Procedure: Stem Cell Transfusion
  • Experimental: Regimen A
    Patients receive cytarabine 3.0gm/M² IV over 1 hour twice daily on days -9 to -7 and cyclophosphamide 45mg/kg IV over 2 hours on days -6 and -5. Patients also undergo total body irradiation (TBI), 165 cGY, twice daily on days -4 to -1 for a total of 1320 cGY.
    Interventions:
    • Drug: cyclophosphamide
    • Drug: cytarabine
    • Radiation: radiation therapy
    • Procedure: Stem Cell Transfusion
  • Experimental: Regimen B-1
    Patients receive cyclophosphamide 60 mg/kg IV on days -6 and -5. Patients also undergo total body irradiation (TBI) twice daily on days -4 to -1 for a total of 1320 cGY..
    Interventions:
    • Drug: cyclophosphamide
    • Radiation: radiation therapy
    • Procedure: Stem Cell Transfusion
  • Experimental: Regimen B-2
    Patients receive cyclophosphamide 60 mg/kg IV over 2 hours on days -5 and -4. Patients also undergo TBI twice daily on days -3 to -1 for a total of 1200 cGY.
    Interventions:
    • Drug: cyclophosphamide
    • Radiation: radiation therapy
    • Procedure: Stem Cell Transfusion
  • Experimental: Regimen C
    Patients receive oral busulfan 1mg/kg/dose (or 40mg/m2/dose for young children)4 times daily on days -8 to -5 and cyclophosphamide 60 mg/kg IV over 2 hours on days -4 to -2.
    Interventions:
    • Drug: busulfan
    • Drug: cyclophosphamide
    • Procedure: Stem Cell Transfusion
  • Experimental: Regimen B-3
    Patients undergo total body irradiation (TBI) twice daily on days -7 to -5 for a total of 1200 cGY. Patients then receive cyclophosphamide 60 mg/kg IV on days -4 and -3.
    Interventions:
    • Drug: cyclophosphamide
    • Radiation: radiation therapy
    • Procedure: Stem Cell Transfusion
  • Experimental: Regimen D
    Patients receive total body irradiation (TBI) on days T -6, -5 and -4 for a total of 1320 cGy , then etoposide (60mg/kg/dose) on day -3.
    Interventions:
    • Radiation: radiation therapy
    • Drug: Etoposide
    • Procedure: Stem Cell Transfusion
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
34
September 2011
September 2011   (final data collection date for primary outcome measure)

Eligibility Criteria:

  1. Patients with histologic confirmation of the following diseases are eligible:

    1. AML in first, second or greater remission
    2. AML in early relapse, defined at <30% marrow blasts
    3. ALL in second or greater complete remission
    4. High risk ALL in first complete remission, with high risk being defined by the presence of t(4;11), t(9;22), or t(8;14) translocation, or patients presenting with extreme hyperleukocytosis (initial WBC >500 K/ml) or failure to achieve a complete remission after standard induction therapy.
    5. CML
    6. Myelodysplastic syndromes (including evolution to AML, e.g., Refractory Anemia with Excess Blasts (RAEB), or Refractory Anemia with Excess Blasts in transformation (RAEB-t).
    7. Lymphoma (intermediate and high grade) chemosensitive (CR or PR) after first or greater relapse or chemosensitive to first line therapy but only achieving PR.
    8. Hematologic Disease and Inherited Immunodeficiencies
    9. Hodgkin's disease, relapsed or refractory to standard treatments.
  2. Patients must be less than or equal to 55 years of age.
  3. Patients (or guardians if minor) must be able to give informed consent. Children older than 11 years of age must assent to the process.
  4. Patients or their guardians must demonstrate proof-of-payment.
  5. Patients must have an ECOG Performance Status of 2 or less. (See Appendix I)
  6. Patients must have no evidence of active infection at the time of transplantation.
  7. Patients must be HIV nonreactive.
  8. Patients must have a pre-transplant, multi-organ assessment prior to transplantation with the following outcome:

    1. resting ejection fraction of 50% or greater (or shortening fraction greater than 28% for small children).
    2. Diffusion capacity of 50% or greater of predicted, a FEV1 of 50% or greater, and a P2O of 80 mm Hg as demonstrated on pulmonary function testing.
    3. serum creatinine of less than or equal to 2.0 mg/dL and/or a corrected creatinine clearance of 50 ml/min or greater on 24 hr urine.
    4. A total bilirubin of less than 2.5 mg/dL and an AST less than 4 times the upper limits of normal.
  9. Females who are childbearing age may not be pregnant or lactating and must have a current negative pregnancy test

Ineligibility Criteria:

  • Patients who have a life expectancy of less than three months with therapy.
  • Patients who have an ECOG performance status greater than 2, (See Appendix I) or Lansky Scale < 70%.
  • Patients who have angina and/or congestive heart failure requiring treatment, or who have had a myocardial infarction within the past year.
  • Patients who have a resting ejection of less than 50% (or shortening fraction less than 28%) and who have not been cleared for transplant by cardiology
  • Patients who have severe renal disease as demonstrated by a serum creatinine greater than 2.0 mg/dL and/or a corrected creatinine clearance less than 50 ml/min. (corrected for BSA of 1.73 m¬2)
  • Patients who have had any complication that makes the risk of death during transplantation from non-malignant causes greater than the risk of relapse.
  • Patients who have any active infection such as a soft tissue infection, sinus infection, dental infection, fungal infection or hepatitis including chronic active hepatitis; if the infection is successfully treated, the patient may be reconsidered for transplantation at a later date.
  • Patients who have decreased pulmonary function due to any disorder as demonstrated by a diffusion capacity of less than 50% of predicted, a FEV1 of less than 50% of predicted or a PO2 of less than 80 mm Hg pulmonary function testing.
  • Patients who have decreased liver function as demonstrated by a total bilirubin of greater than 2.5 mg/dL and/or an AST greater than 4 times the upper limits of normal.
  • Patients who have diabetes mellitus will be considered on a case-by-case basis. However, patients with diabetes who are not controlled by medical management will be ineligible.

-Patients who have a significant psychiatric illness will be considered on a case- by-case basis. With the patient's consent, their Mental Health Care worker will assist the managing transplant physicians in determining if the patient can safely undergo transplantation and comply with followup recommendations.

  • Psychosocial assessment by the bone marrow transplant team may identify individuals for whom this form of therapy may be contraindicated. This decision will be based upon estimated adequacy of patient support systems and prediction of patient's compliance with medications, required diagnostic procedures and/or follow-up care.
  • Females who are childbearing age may not be pregnant or lactating and must have a current negative pregnancy test
  • Patients who had a stem cell transplant less than one year earlier
Both
up to 55 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00054327
CWRU1Y00, P30CA043703, CASE-CWRU-1Y00
Yes
Case Comprehensive Cancer Center
Case Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Kenneth Cooke, MD Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Case Comprehensive Cancer Center
June 2013

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