Umbilical Cord Blood Transplantation in Treating Patients With High-Risk Hematologic Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00003335
First received: November 1, 1999
Last updated: March 14, 2012
Last verified: March 2012
  Purpose

RATIONALE: Umbilical cord blood transplantation may allow doctors to give higher doses of chemotherapy or radiation therapy and kill more cancer cells.

PURPOSE: This phase II trial is studying allogeneic umbilical cord blood transplantation to see how well it works when given with chemotherapy or radiation therapy in treating patients with high-risk hematologic cancer.


Condition Intervention Phase
Graft Versus Host Disease
Leukemia
Lymphoma
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Biological: anti-thymocyte globulin
Drug: busulfan
Drug: cyclosporine
Drug: melphalan
Drug: methylprednisolone
Procedure: umbilical cord blood transplantation
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Unrelated Umbilical Cord Blood Transplantation in Patients With High Risk Hematologic Malignancies

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: Acute Erythroblastic Leukemia Acute Erythroid Leukemia Acute Lymphoblastic Leukemia Acute Lymphoblastic Leukemia, Childhood Acute Megakaryoblastic Leukemia Acute Myelocytic Leukemia Acute Myeloid Leukemia, Adult Acute Myeloid Leukemia, Childhood Acute Non Lymphoblastic Leukemia B-cell Lymphomas Burkitt Lymphoma Chronic Lymphocytic Leukemia Chronic Myeloid Leukemia Chronic Myeloproliferative Disorders Di Guglielmo's Syndrome Follicular Lymphoma Homologous Wasting Disease Leukemia, B-cell, Chronic Leukemia, Myeloid Lymphoblastic Lymphoma Lymphoma, Large-cell Lymphoma, Large-cell, Immunoblastic Lymphoma, Small Cleaved-cell, Diffuse Lymphosarcoma Mantle Cell Lymphoma Myelodysplastic Syndromes Myelodysplastic/myeloproliferative Disease Plasmablastic Lymphoma Small Non-cleaved Cell Lymphoma
U.S. FDA Resources

Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • rates of durable engraftment in patients [ Time Frame: day 42 ] [ Designated as safety issue: No ]
    The primary study end point will be hematologic engraftment. Engraftment is defined as achieving ANC larger than or equal to 500 ul/mm3 of donor origin for three consecutive measurements on different days by day +42.


Secondary Outcome Measures:
  • Event-free survival by clinical and pathological disease assessment [ Time Frame: at disease progression or death ] [ Designated as safety issue: No ]
  • incidence of recurrent disease in patients post UCB transplant [ Time Frame: post transplant ] [ Designated as safety issue: No ]

Enrollment: 44
Study Start Date: January 1998
Study Completion Date: January 2012
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: anti-thymocyte globulin
    antithymocyte globulin IV for three days on days -3 to -1
    Drug: busulfan
    If TBI is not tolerated, busulfan is substituted and administered orally every 6 hours for 4 days on days -8 to -5.
    Drug: cyclosporine
    Cyclosporine begin on day -2 and continue for 6 months.
    Drug: melphalan
    melphalan IV for three days on days -4 to -2
    Drug: methylprednisolone
    Methylprednisolone IV for three days on days -3 to -1. Methylprednisolone begin on day -2 and continue for 6 months.
    Procedure: umbilical cord blood transplantation
    On day 0, patients receive umbilical cord blood infusion.
    Radiation: radiation therapy
    9 fractions of total body irradiation (TBI) on days -9 to -5
Detailed Description:

OBJECTIVES:

  • Determine the rates of hematologic and immune reconstitution in patients with high risk hematologic malignancies who are undergoing high dose chemoradiotherapy followed by unrelated umbilical cord blood (UCB) transplantation.
  • Determine the incidence of graft-versus-host-disease in this setting.
  • Describe the incidence of recurrent disease in these patients post UCB transplant.
  • Describe the incidence of serious infections and secondary lymphoproliferative diseases following transplantation with UCB in these patients.
  • Determine specifically whether larger recipients can be durably engrafted with unrelated UCB, and determine whether nucleated cell or progenitor cell content of the graft is predictive of hematological engraftment.

OUTLINE: Patients may undergo a back-up peripheral blood stem cell collection prior to treatment.

Patients receive 9 fractions of total body irradiation (TBI) on days -9 to -5 followed by melphalan IV for three days on days -4 to -2 and antithymocyte globulin IV or methylprednisolone IV for three days on days -3 to -1. On day 0, patients receive umbilical cord blood infusion. If TBI is not tolerated, busulfan is substituted and administered orally every 6 hours for 4 days on days -8 to -5. Cyclosporine and methylprednisolone begin on day -2 and continue for 6 months.

Patients are followed at least monthly for 1 year, then every 6 months for the second year, and then annually thereafter.

PROJECTED ACCRUAL: There will be a maximum of 48 patients accrued into this study over 4 years.

  Eligibility

Ages Eligible for Study:   up to 54 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed high risk malignancy including:

    • Acute nonlymphocytic leukemia (ANLL) after induction failure, or in first complete remission with high risk features including stem cell or biphenotypic classification (acute myeloid leukemia (AML) M0), erythroleukemia (AML M6), acute megakaryocytic leukemia (AML M7), cytogenic markers indicative of poor prognosis, or failure to achieve complete remission after standard induction therapy
    • Acute lymphocytic leukemia (ALL) or ANLL in second or subsequent remission
    • Chronic myeloid leukemia (CML) in chronic phase

      • CML with accelerated phase or blast crisis are eligible after reinduction chemotherapy converts disease to chronic phase
    • High risk ALL in first complete remission
    • Myelodysplastic syndrome with evidence of evolution to acute myeloid leukemia

      • Refractory anemia with excess blasts
      • Refractory anemia with excess blasts in transformation
    • Non-Hodgkin's lymphoma (NHL), ANLL, or ALL with recurrent disease after autologous stem cell transplantation
  • Must also meet all the following conditions:

    • No HLA-ABC/DR identical related bone marrow or UCB donor
    • No 5/6 antigen matched related bone marrow or UCB donor
    • Condition precludes waiting to search and find a donor in the National Marrow Donor Registry
  • Must have an available serologic matched umbilical cord blood unit in the New York Blood Center's Placental Blood Project
  • No active CNS disease

PATIENT CHARACTERISTICS:

Age:

  • Under 55 at time of umbilical cord blood transplantation

Performance status:

  • Zubrod 0-1
  • Karnofsky 80-100%

Life expectancy:

  • At least 3 months

Hematopoietic:

  • For patients with ALL or ANLL in remission, CML in chronic phase, or NHL without marrow involvement who elect to undergo autologous peripheral blood stem cell collection and storage:

    • WBC at least 3,000/mm^3
    • Absolute neutrophil count at least 1,000/mm^3
    • Platelet count at least 100,000/mm^3

Hepatic:

  • Bilirubin no greater than 2.0 mg/dL
  • ALT/AST no greater than 4 times normal

Renal:

  • Creatinine no greater than 2.0 mg/dL
  • Creatinine clearance at least 50 mL/min

Cardiovascular:

  • Normal cardiac function by echocardiogram or radionuclide scan (shortening fraction or ejection fraction at least 80% of normal value for age)

Pulmonary:

  • FVC and FEV_1 at least 60% of predicted for age
  • For adults:

    • DLCO at least 60% of predicted

Other:

  • HIV negative
  • No active infections at time of autologous stem cell harvest or pretransplant cytoreduction
  • Not pregnant or nursing
  • Effective contraception required of all fertile patients

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Prior autologous stem cell transplantation allowed

Chemotherapy:

  • See Disease Characteristics

Endocrine therapy:

  • Not specified

Radiotherapy:

  • Not specified

Surgery:

  • Not specified
  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: NCT00003335

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
Study Chair: Brenda W. Cooper, MD Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00003335     History of Changes
Other Study ID Numbers: CWRU4Y97, P30CA043703, NCI-G98-1429, CWRU4Y97
Study First Received: November 1, 1999
Last Updated: March 14, 2012
Health Authority: United States: Federal Government

Keywords provided by Case Comprehensive Cancer Center:
adult acute erythroid leukemia (M6)
childhood acute erythroleukemia (M6)
recurrent childhood acute lymphoblastic leukemia
recurrent childhood lymphoblastic lymphoma
recurrent adult acute lymphoblastic leukemia
chronic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
untreated childhood acute lymphoblastic leukemia
adult acute myeloid leukemia in remission
adult acute lymphoblastic leukemia in remission
childhood acute myeloid leukemia in remission
childhood acute lymphoblastic leukemia in remission
adult acute megakaryoblastic leukemia (M7)
childhood acute megakaryocytic leukemia (M7)
refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
graft versus host disease

Additional relevant MeSH terms:
Graft vs Host Disease
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
Antilymphocyte Serum
Cyclosporine
Cyclosporins
Melphalan
Methylprednisolone
Methylprednisolone acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate

ClinicalTrials.gov processed this record on October 22, 2014