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Fludarabine, Cyclophosphamide, and Total-Body Irradiation Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients Who Are Undergoing a Donor Umbilical Cord Blood Transplant for Hematologic Cancer

Primary Purpose

Chronic Myeloproliferative Disorders, Graft Versus Host Disease, Leukemia

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
graft-versus-tumor induction therapy
cyclophosphamide
cyclosporine
fludarabine phosphate
mycophenolate mofetil
umbilical cord blood transplantation
radiation therapy
Sponsored by
University of Rochester
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Myeloproliferative Disorders focused on measuring graft versus host disease, adult acute myeloid leukemia in remission, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), recurrent adult acute myeloid leukemia, childhood acute myeloid leukemia in remission, recurrent childhood acute myeloid leukemia, adult acute lymphoblastic leukemia in remission, recurrent adult acute lymphoblastic leukemia, childhood acute lymphoblastic leukemia in remission, recurrent childhood acute lymphoblastic leukemia, acute undifferentiated leukemia, accelerated phase chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, childhood chronic myelogenous leukemia, refractory anemia with excess blasts, refractory anemia, chronic myelomonocytic leukemia, atypical chronic myeloid leukemia, BCR-ABL1 negative, juvenile myelomonocytic leukemia, primary myelofibrosis, refractory hairy cell leukemia, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma, refractory chronic lymphocytic leukemia, stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, recurrent/refractory childhood Hodgkin lymphoma, stage III adult Burkitt lymphoma, stage IV adult Burkitt lymphoma, stage III adult diffuse large cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage III adult lymphoblastic lymphoma, stage IV adult lymphoblastic lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage III mantle cell lymphoma, stage III marginal zone lymphoma, stage IV mantle cell lymphoma, stage IV marginal zone lymphoma, stage III small lymphocytic lymphoma, stage IV 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 inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), de novo myelodysplastic syndromes, recurrent mycosis fungoides/Sezary syndrome, recurrent cutaneous T-cell non-Hodgkin lymphoma, recurrent childhood large cell lymphoma, recurrent childhood lymphoblastic lymphoma, recurrent childhood small noncleaved cell lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, recurrent adult Burkitt lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent mantle cell lymphoma, relapsing chronic myelogenous leukemia, myelodysplastic/myeloproliferative neoplasm, unclassifiable, previously treated myelodysplastic syndromes, recurrent adult Hodgkin lymphoma, secondary acute myeloid leukemia, secondary myelodysplastic syndromes, noncontiguous stage II adult Burkitt lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse mixed cell lymphoma, noncontiguous stage II adult diffuse small cleaved cell lymphoma, noncontiguous stage II adult immunoblastic large cell lymphoma, noncontiguous stage II adult lymphoblastic lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, noncontiguous stage II grade 3 follicular lymphoma, noncontiguous stage II mantle cell lymphoma, noncontiguous stage II marginal zone lymphoma, noncontiguous stage II small lymphocytic lymphoma, childhood myelodysplastic syndromes

Eligibility Criteria

undefined - 75 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Diagnosis of 1 of the following hematologic malignancies: Acute myeloid leukemia (AML) with or without history of myelodysplastic syndromes, meeting 1 of the following criteria: In first complete remission (CR-1) with unfavorable cytogenetics and/or achieved CR-1 after ≥ 1 course of induction therapy Secondary or treatment-related AML In second or further complete remission Relapsed with ≤ 20% blasts in the bone marrow AND no circulating blasts Acute lymphoblastic leukemia (ALL), meeting 1 of the following criteria: In CR-1 with unfavorable cytogenetics or elevated WBC at presentation OR failed to achieve CR-1 after ≥ 4 weeks of induction therapy In second or further complete remission Relapsed with ≤ 20% blasts in the bone marrow AND no circulating blasts Other acute leukemic variants allowed at the discretion of the principal investigator Chronic myelogenous leukemia (CML), meeting 1 of the following criteria: In first chronic phase AND refractory to or unable to tolerate imatinib mesylate In second or further chronic phase In first or second accelerated phase Myelodysplastic syndromes with intermediate 2- or high-risk International Prognosis Scoring System (IPSS) score, including any of the following: Refractory anemia Refractory anemia with excess blasts Chronic myelomonocytic leukemia Myeloproliferative disorders with poor prognosis, including any of the following: Myelofibrosis with myeloid metaplasia No ≥ grade 3 myelofibrosis Atypical CML Juvenile myelomonocytic leukemia Other clonal hemopathies with an accepted poor prognosis Multiple myeloma with chromosome 13 abnormalities and/or progression after prior autologous bone marrow transplantation (BMT) Chronic lymphocytic leukemia, meeting 1 of the following criteria: Primary refractory OR relapsed and refractory disease (less than partial remission) Relapsed twice on or after prior chemotherapy Lymphoma, meeting both of the following criteria: Hodgkin's or non-Hodgkin's lymphoma in > CR-1 OR failed primary induction Chemosensitive disease, defined as > 50% reduction in mass size after the most recent chemotherapy Must meet ≥ 1 of the following criteria: Over 45 years of age Has undergone prior autologous or allogeneic BMT Charlson^ comorbidity score ≥ 2 Must have a high degree of tumor control (salvage therapy allowed) At high risk for treatment-related mortality with a myeloablative conditioning regimen No massive splenomegaly Patients may become eligible after splenectomy or radiotherapy to the spleen No 5/6 or 6/6 HLA-matched related donor available No well-matched (i.e., ≥ 9/10 HLA match by high-resolution typing) unrelated donor available PATIENT CHARACTERISTICS: Performance status Not specified Life expectancy Not specified Hematopoietic See Disease Characteristics Hepatic Bilirubin ≤ 2 times upper limit of normal (ULN) Transaminases ≤ 4 times ULN (unless due to underlying disease) Renal Creatinine clearance ≥ 50 mL/min Cardiovascular Ejection fraction ≥ 30% Pulmonary DCLO ≥ 35% Other Negative pregnancy test No uncontrolled viral, bacterial, or fungal infection HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics Chemotherapy See Disease Characteristics Radiotherapy See Disease Characteristics Other At least 3 months since prior immunosuppressive therapy At least 10 days since prior salvage therapy for patients not in at least morphologic or radiologic complete remission

Sites / Locations

  • James P. Wilmot Cancer Center at University of Rochester Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Conditioning therapy followed by TBI

Arm Description

Fludarabine, Cyclophosphamide; Total-Body Irradiation Followed by Cyclosporine and Mycophenolate Mofetil

Outcomes

Primary Outcome Measures

Number of Participants Who Survived 100 Days or Longer

Secondary Outcome Measures

Number of Participants Who Developed Acute Graft Versus Host Disease

Full Information

First Posted
November 18, 2005
Last Updated
September 28, 2016
Sponsor
University of Rochester
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1. Study Identification

Unique Protocol Identification Number
NCT00255684
Brief Title
Fludarabine, Cyclophosphamide, and Total-Body Irradiation Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients Who Are Undergoing a Donor Umbilical Cord Blood Transplant for Hematologic Cancer
Official Title
Non-Myeloablative Conditioning and Unrelated Umbilical Cord Blood Transplantation for Children and Adults With Serious Oncohematologic Diseases
Study Type
Interventional

2. Study Status

Record Verification Date
September 2016
Overall Recruitment Status
Terminated
Why Stopped
low accrual
Study Start Date
December 2003 (undefined)
Primary Completion Date
March 2013 (Actual)
Study Completion Date
June 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Rochester

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Giving low doses of chemotherapy, such as fludarabine and cyclophosphamide, and radiation therapy before a donor umbilical cord blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after transplant may stop this from happening. PURPOSE: This clinical trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation followed by cyclosporine and mycophenolate mofetil works in treating patients who are undergoing a donor umbilical cord blood transplant for hematologic cancer.
Detailed Description
OBJECTIVES: Determine the frequency, extent, and rate of donor (myeloid and lymphoid) engraftment in patients with serious hematologic malignancies treated with nonmyeloablative conditioning regimen comprising fludarabine, cyclophosphamide, and low-dose total-body irradiation followed by unrelated allogeneic umbilical cord blood transplantation and post-transplant immunosuppression comprising cyclosporine and mycophenolate mofetil. Correlate clinical and umbilical cord blood-related factors with engraftment in patients treated with this regimen. Determine transplant-related complications, in terms of toxicity, myelosuppression, infections, and acute and chronic graft-versus-host disease, in patients treated with this regimen. Determine disease-free and overall survival of patients treated with this regimen. Determine treatment-related mortality of patients treated with this regimen. OUTLINE: This is a uncontrolled, pilot study. Nonmyeloablative conditioning regimen: Patients receive fludarabine IV over 30 minutes daily on days -6 to -2 and cyclophosphamide IV over 2 hours on day -6 and undergo low-dose total-body irradiation (TBI) on day 0. Unrelated allogeneic umbilical cord blood transplantation (UCBT): After completion of TBI, patients undergo 1 or 2 unrelated allogeneic UCBTs on day 0. Post-transplant immunosuppression: Patients receive oral or IV cyclosporine daily beginning on day -3 and continuing until day 180 and oral or IV mycophenolate mofetil twice daily on days 0-30. Patients are followed periodically for 1 year after transplantation. PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myeloproliferative Disorders, Graft Versus Host Disease, Leukemia, Lymphoma, Multiple Myeloma, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
Keywords
graft versus host disease, adult acute myeloid leukemia in remission, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), recurrent adult acute myeloid leukemia, childhood acute myeloid leukemia in remission, recurrent childhood acute myeloid leukemia, adult acute lymphoblastic leukemia in remission, recurrent adult acute lymphoblastic leukemia, childhood acute lymphoblastic leukemia in remission, recurrent childhood acute lymphoblastic leukemia, acute undifferentiated leukemia, accelerated phase chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, childhood chronic myelogenous leukemia, refractory anemia with excess blasts, refractory anemia, chronic myelomonocytic leukemia, atypical chronic myeloid leukemia, BCR-ABL1 negative, juvenile myelomonocytic leukemia, primary myelofibrosis, refractory hairy cell leukemia, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma, refractory chronic lymphocytic leukemia, stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, recurrent/refractory childhood Hodgkin lymphoma, stage III adult Burkitt lymphoma, stage IV adult Burkitt lymphoma, stage III adult diffuse large cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage III adult lymphoblastic lymphoma, stage IV adult lymphoblastic lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage III mantle cell lymphoma, stage III marginal zone lymphoma, stage IV mantle cell lymphoma, stage IV marginal zone lymphoma, stage III small lymphocytic lymphoma, stage IV 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 inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), de novo myelodysplastic syndromes, recurrent mycosis fungoides/Sezary syndrome, recurrent cutaneous T-cell non-Hodgkin lymphoma, recurrent childhood large cell lymphoma, recurrent childhood lymphoblastic lymphoma, recurrent childhood small noncleaved cell lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, recurrent adult Burkitt lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent mantle cell lymphoma, relapsing chronic myelogenous leukemia, myelodysplastic/myeloproliferative neoplasm, unclassifiable, previously treated myelodysplastic syndromes, recurrent adult Hodgkin lymphoma, secondary acute myeloid leukemia, secondary myelodysplastic syndromes, noncontiguous stage II adult Burkitt lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse mixed cell lymphoma, noncontiguous stage II adult diffuse small cleaved cell lymphoma, noncontiguous stage II adult immunoblastic large cell lymphoma, noncontiguous stage II adult lymphoblastic lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, noncontiguous stage II grade 3 follicular lymphoma, noncontiguous stage II mantle cell lymphoma, noncontiguous stage II marginal zone lymphoma, noncontiguous stage II small lymphocytic lymphoma, childhood myelodysplastic syndromes

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Conditioning therapy followed by TBI
Arm Type
Experimental
Arm Description
Fludarabine, Cyclophosphamide; Total-Body Irradiation Followed by Cyclosporine and Mycophenolate Mofetil
Intervention Type
Biological
Intervention Name(s)
graft-versus-tumor induction therapy
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
cyclosporine
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate
Intervention Type
Drug
Intervention Name(s)
mycophenolate mofetil
Intervention Type
Procedure
Intervention Name(s)
umbilical cord blood transplantation
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Primary Outcome Measure Information:
Title
Number of Participants Who Survived 100 Days or Longer
Time Frame
100 days
Secondary Outcome Measure Information:
Title
Number of Participants Who Developed Acute Graft Versus Host Disease
Time Frame
3 months

10. Eligibility

Sex
All
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of 1 of the following hematologic malignancies: Acute myeloid leukemia (AML) with or without history of myelodysplastic syndromes, meeting 1 of the following criteria: In first complete remission (CR-1) with unfavorable cytogenetics and/or achieved CR-1 after ≥ 1 course of induction therapy Secondary or treatment-related AML In second or further complete remission Relapsed with ≤ 20% blasts in the bone marrow AND no circulating blasts Acute lymphoblastic leukemia (ALL), meeting 1 of the following criteria: In CR-1 with unfavorable cytogenetics or elevated WBC at presentation OR failed to achieve CR-1 after ≥ 4 weeks of induction therapy In second or further complete remission Relapsed with ≤ 20% blasts in the bone marrow AND no circulating blasts Other acute leukemic variants allowed at the discretion of the principal investigator Chronic myelogenous leukemia (CML), meeting 1 of the following criteria: In first chronic phase AND refractory to or unable to tolerate imatinib mesylate In second or further chronic phase In first or second accelerated phase Myelodysplastic syndromes with intermediate 2- or high-risk International Prognosis Scoring System (IPSS) score, including any of the following: Refractory anemia Refractory anemia with excess blasts Chronic myelomonocytic leukemia Myeloproliferative disorders with poor prognosis, including any of the following: Myelofibrosis with myeloid metaplasia No ≥ grade 3 myelofibrosis Atypical CML Juvenile myelomonocytic leukemia Other clonal hemopathies with an accepted poor prognosis Multiple myeloma with chromosome 13 abnormalities and/or progression after prior autologous bone marrow transplantation (BMT) Chronic lymphocytic leukemia, meeting 1 of the following criteria: Primary refractory OR relapsed and refractory disease (less than partial remission) Relapsed twice on or after prior chemotherapy Lymphoma, meeting both of the following criteria: Hodgkin's or non-Hodgkin's lymphoma in > CR-1 OR failed primary induction Chemosensitive disease, defined as > 50% reduction in mass size after the most recent chemotherapy Must meet ≥ 1 of the following criteria: Over 45 years of age Has undergone prior autologous or allogeneic BMT Charlson^ comorbidity score ≥ 2 Must have a high degree of tumor control (salvage therapy allowed) At high risk for treatment-related mortality with a myeloablative conditioning regimen No massive splenomegaly Patients may become eligible after splenectomy or radiotherapy to the spleen No 5/6 or 6/6 HLA-matched related donor available No well-matched (i.e., ≥ 9/10 HLA match by high-resolution typing) unrelated donor available PATIENT CHARACTERISTICS: Performance status Not specified Life expectancy Not specified Hematopoietic See Disease Characteristics Hepatic Bilirubin ≤ 2 times upper limit of normal (ULN) Transaminases ≤ 4 times ULN (unless due to underlying disease) Renal Creatinine clearance ≥ 50 mL/min Cardiovascular Ejection fraction ≥ 30% Pulmonary DCLO ≥ 35% Other Negative pregnancy test No uncontrolled viral, bacterial, or fungal infection HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics Chemotherapy See Disease Characteristics Radiotherapy See Disease Characteristics Other At least 3 months since prior immunosuppressive therapy At least 10 days since prior salvage therapy for patients not in at least morphologic or radiologic complete remission
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gordon L. Phillips, MD
Organizational Affiliation
James P. Wilmot Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
James P. Wilmot Cancer Center at University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Fludarabine, Cyclophosphamide, and Total-Body Irradiation Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients Who Are Undergoing a Donor Umbilical Cord Blood Transplant for Hematologic Cancer

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