Clinical trial NCT00255684: 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
Overall status: TERMINATED
Phase: NA
Conditions: 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
Lead sponsor: University of Rochester
Sponsor class: OTHER
First posted: 2005-11-21
Enrollment: 16
Sex: ALL
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants Who Survived 100 Days or Longer
timeFrame: 100 days
Secondary outcomes:
measure: Number of Participants Who Developed Acute Graft Versus Host Disease
timeFrame: 3 months
Other outcomes:
Locations:
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
Study officials:
affiliation: James P. Wilmot Cancer Center
name: Gordon L. Phillips, MD
role: PRINCIPAL_INVESTIGATOR
References: