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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
  Purpose

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.


Condition Intervention Phase
Leukemia
Lymphoma
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Drug: busulfan
Drug: cyclophosphamide
Drug: cytarabine
Radiation: radiation therapy
Drug: Etoposide
Procedure: Stem Cell Transfusion
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Hematopoietic Stem Cell Transplantation Using Bone Marrow Or Peripheral Blood Stem Cells From Matched, Unrelated, Volunteer Donors

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 34
Study Start Date: November 2000
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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..
Drug: cyclophosphamide
Given IV
Other Names:
  • cytoxan
  • CTX
  • CPM
Radiation: radiation therapy
Patients undergo total body irradiation
Other Name: Total body irradiation
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.
Drug: cyclophosphamide
Given IV
Other Names:
  • cytoxan
  • CTX
  • CPM
Radiation: radiation therapy
Patients undergo total body irradiation
Other Name: Total body irradiation
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.
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
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.
Drug: cyclophosphamide
Given IV
Other Names:
  • cytoxan
  • CTX
  • CPM
Radiation: radiation therapy
Patients undergo total body irradiation
Other Name: Total body irradiation
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.
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

Detailed Description:

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

  Eligibility

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

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
  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: NCT00054327

Locations
United States, Ohio
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Principal Investigator: Kenneth Cooke, MD Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00054327     History of Changes
Other Study ID Numbers: CWRU1Y00, P30CA043703, CASE-CWRU-1Y00
Study First Received: February 5, 2003
Results First Received: April 30, 2013
Last Updated: June 19, 2013
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by Case Comprehensive Cancer Center:
adult acute myeloid leukemia in remission
childhood acute myeloid leukemia in remission
recurrent adult acute myeloid leukemia
recurrent childhood acute myeloid leukemia
adult acute lymphoblastic leukemia in remission
childhood acute lymphoblastic leukemia in remission
refractory anemia with excess blasts in transformation
refractory anemia with excess blasts
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult Burkitt lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent grade 3 follicular lymphoma
secondary acute myeloid leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
recurrent childhood large cell lymphoma
recurrent childhood lymphoblastic lymphoma
recurrent childhood small noncleaved cell lymphoma
recurrent mantle cell lymphoma
refractory anemia with ringed sideroblasts
refractory anemia
chronic myelomonocytic leukemia
refractory cytopenia with multilineage dysplasia
previously treated myelodysplastic syndromes
de novo myelodysplastic syndromes
secondary myelodysplastic syndromes

Additional relevant MeSH terms:
Leukemia
Lymphoma
Myelodysplastic Syndromes
Myelodysplastic-Myeloproliferative Diseases
Myeloproliferative Disorders
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
Cyclophosphamide
Cytarabine
Etoposide
Alkylating Agents
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Antiviral Agents

ClinicalTrials.gov processed this record on November 25, 2014