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

Primary Purpose

Graft Versus Host Disease, Leukemia, Lymphoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
anti-thymocyte globulin
busulfan
cyclosporine
melphalan
methylprednisolone
umbilical cord blood transplantation
radiation therapy
Sponsored by
Case Comprehensive Cancer Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Graft Versus Host Disease focused on measuring 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 erythroid leukemia (M6), adult acute megakaryoblastic leukemia (M7), childhood acute erythroleukemia (M6), 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, adult acute minimally differentiated myeloid leukemia (M0), childhood acute minimally differentiated myeloid leukemia (M0), recurrent childhood small noncleaved cell lymphoma, recurrent childhood large cell lymphoma, recurrent mantle cell lymphoma, childhood chronic myelogenous leukemia, atypical chronic myeloid leukemia, myelodysplastic/myeloproliferative disease, unclassifiable, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with t(15;17)(q22;q12), childhood myelodysplastic syndromes

Eligibility Criteria

undefined - 54 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Outcomes

Primary Outcome Measures

rates of durable engraftment in patients
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
incidence of recurrent disease in patients post UCB transplant

Full Information

First Posted
November 1, 1999
Last Updated
March 14, 2012
Sponsor
Case Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00003335
Brief Title
Umbilical Cord Blood Transplantation in Treating Patients With High-Risk Hematologic Cancer
Official Title
A Pilot Study of Unrelated Umbilical Cord Blood Transplantation in Patients With High Risk Hematologic Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
March 2012
Overall Recruitment Status
Completed
Study Start Date
January 1998 (undefined)
Primary Completion Date
November 2007 (Actual)
Study Completion Date
January 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Case Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft Versus Host Disease, Leukemia, Lymphoma, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases
Keywords
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 erythroid leukemia (M6), adult acute megakaryoblastic leukemia (M7), childhood acute erythroleukemia (M6), 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, adult acute minimally differentiated myeloid leukemia (M0), childhood acute minimally differentiated myeloid leukemia (M0), recurrent childhood small noncleaved cell lymphoma, recurrent childhood large cell lymphoma, recurrent mantle cell lymphoma, childhood chronic myelogenous leukemia, atypical chronic myeloid leukemia, myelodysplastic/myeloproliferative disease, unclassifiable, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with t(15;17)(q22;q12), childhood myelodysplastic syndromes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
44 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
anti-thymocyte globulin
Intervention Description
antithymocyte globulin IV for three days on days -3 to -1
Intervention Type
Drug
Intervention Name(s)
busulfan
Intervention Description
If TBI is not tolerated, busulfan is substituted and administered orally every 6 hours for 4 days on days -8 to -5.
Intervention Type
Drug
Intervention Name(s)
cyclosporine
Intervention Description
Cyclosporine begin on day -2 and continue for 6 months.
Intervention Type
Drug
Intervention Name(s)
melphalan
Intervention Description
melphalan IV for three days on days -4 to -2
Intervention Type
Drug
Intervention Name(s)
methylprednisolone
Intervention Description
Methylprednisolone IV for three days on days -3 to -1. Methylprednisolone begin on day -2 and continue for 6 months.
Intervention Type
Procedure
Intervention Name(s)
umbilical cord blood transplantation
Intervention Description
On day 0, patients receive umbilical cord blood infusion.
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Intervention Description
9 fractions of total body irradiation (TBI) on days -9 to -5
Primary Outcome Measure Information:
Title
rates of durable engraftment in patients
Description
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.
Time Frame
day 42
Secondary Outcome Measure Information:
Title
Event-free survival by clinical and pathological disease assessment
Time Frame
at disease progression or death
Title
incidence of recurrent disease in patients post UCB transplant
Time Frame
post transplant

10. Eligibility

Sex
All
Maximum Age & Unit of Time
54 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brenda W. Cooper, MD
Organizational Affiliation
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106-5065
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
18769450
Citation
Lesniewski ML, Haviernik P, Weitzel RP, Kadereit S, Kozik MM, Fanning LR, Yang YC, Hegerfeldt Y, Finney MR, Ratajczak MZ, Greco N, Paul P, Maciejewski J, Laughlin MJ. Regulation of IL-2 expression by transcription factor BACH2 in umbilical cord blood CD4+ T cells. Leukemia. 2008 Dec;22(12):2201-7. doi: 10.1038/leu.2008.234. Epub 2008 Sep 4.
Results Reference
result
PubMed Identifier
17910637
Citation
van Heeckeren WJ, Fanning LR, Meyerson HJ, Fu P, Lazarus HM, Cooper BW, Tse WW, Kindwall-Keller TL, Jaroscak J, Finney MR, Fox RM, Solchaga L, Forster M, Creger RJ, Laughlin MJ. Influence of human leucocyte antigen disparity and graft lymphocytes on allogeneic engraftment and survival after umbilical cord blood transplant in adults. Br J Haematol. 2007 Nov;139(3):464-74. doi: 10.1111/j.1365-2141.2007.06824.x.
Results Reference
result
PubMed Identifier
22002488
Citation
Kindwall-Keller TL, Hegerfeldt Y, Meyerson HJ, Margevicius S, Fu P, van Heeckeren W, Lazarus HM, Cooper BW, Gerson SL, Barr P, Tse WW, Curtis C, Fanning LR, Creger RJ, Carlson-Barko JM, Laughlin MJ. Prospective study of one- vs two-unit umbilical cord blood transplantation following reduced intensity conditioning in adults with hematological malignancies. Bone Marrow Transplant. 2012 Jul;47(7):924-33. doi: 10.1038/bmt.2011.195. Epub 2011 Oct 17.
Results Reference
derived
PubMed Identifier
19286996
Citation
Weitzel RP, Lesniewski ML, Haviernik P, Kadereit S, Leahy P, Greco NJ, Laughlin MJ. microRNA 184 regulates expression of NFAT1 in umbilical cord blood CD4+ T cells. Blood. 2009 Jun 25;113(26):6648-57. doi: 10.1182/blood-2008-09-181156. Epub 2009 Mar 13.
Results Reference
derived

Learn more about this trial

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

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