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

NCT ID: NCT00255684

Last Updated: 2016-11-03

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-12-31

Study Completion Date

2016-06-30

Brief Summary

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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

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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.

Conditions

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Chronic Myeloproliferative Disorders Graft Versus Host Disease Leukemia Lymphoma Multiple Myeloma Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms

Keywords

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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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Conditioning therapy followed by TBI

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

Group Type EXPERIMENTAL

graft-versus-tumor induction therapy

Intervention Type BIOLOGICAL

cyclophosphamide

Intervention Type DRUG

cyclosporine

Intervention Type DRUG

fludarabine phosphate

Intervention Type DRUG

mycophenolate mofetil

Intervention Type DRUG

umbilical cord blood transplantation

Intervention Type PROCEDURE

radiation therapy

Intervention Type RADIATION

Interventions

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graft-versus-tumor induction therapy

Intervention Type BIOLOGICAL

cyclophosphamide

Intervention Type DRUG

cyclosporine

Intervention Type DRUG

fludarabine phosphate

Intervention Type DRUG

mycophenolate mofetil

Intervention Type DRUG

umbilical cord blood transplantation

Intervention Type PROCEDURE

radiation therapy

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

* 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
Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Rochester

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gordon L. Phillips, MD

Role: PRINCIPAL_INVESTIGATOR

James P. Wilmot Cancer Center

Locations

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

Rochester, New York, United States

Site Status

Countries

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United States

Other Identifiers

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URCC-U19403

Identifier Type: -

Identifier Source: secondary_id

URCC-RSRB-10063

Identifier Type: -

Identifier Source: secondary_id

CDR0000448637

Identifier Type: -

Identifier Source: org_study_id