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Transplantation of Unrelated Donor Umbilical Cord Blood in Patients With Hematological Malignancies Using a Non-Myeloablative Preparative Regimen


Phase 2
N/A
69 Years
Not Enrolling
Both
Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases

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Trial Information

Transplantation of Unrelated Donor Umbilical Cord Blood in Patients With Hematological Malignancies Using a Non-Myeloablative Preparative Regimen


OBJECTIVES:

Primary

- To estimate the probability of survival at 1 year in patients with advanced
hematological malignancies or other diseases treated with non-myeloablative unrelated
donor umbilical cord blood transplantation.

Secondary

- Six month non-relapse mortality.

- Chimerism at days 7, 14, 21, 28, 56, and 80, at 6 months, and at 1 and 2 years.

- To determine the incidence of neutrophil engraftment at day 42.

- To determine the incidence of platelet engraftment at 6 months.

- To determine the incidence of grade II-IV and III-IV acute graft-versus-host-disease
(GVHD) at day 100.

- To determine the incidence of chronic GVHD at 1 year.

- To determine the incidence of clinically significant infections at 6 months and at 1
and 2 years.

- To determine the probability of progression-free survival at 1 and 2 years.

- To determine the probability of survival at 2 years.

- To determine the incidence of relapse or disease progression at 1 and 2 years.

OUTLINE: Patients are stratified according to disease status and prior therapy (hematologic
malignancy or other disease that was treated with an autologous stem cell transplant or ≥ 2
courses of multiagent chemotherapy within the past 3 months vs hematologic malignancy or
other disease that was treated with an autologous stem cell transplant > 12 months ago or
with ≤ 1 course of multiagent chemotherapy or immunosuppressive chemotherapy within the past
3 months vs refractory leukemia or lymphoma for which patient was rendered aplastic either
by induction chemotherapy or radioimmunoconjugated monoclonal antibody therapy).

- Conditioning regimen: Patients receive fludarabine phosphate IV over 1 hour on days -6
to -2 and cyclophosphamide IV on day -6. Patients also undergo total body irradiation
on day -1. Some patients also receive anti-thymocyte globulin IV on days -6 to -4.

- Umbilical cord blood transplantation (UCBT): Patients undergo UCBT on day 0.

- Immunosuppressive therapy (graft-versus-host disease prophylaxis): Patients receive
cyclosporine IV over 1 hour or orally (as tolerated) every 8 or 12 hours beginning on
day -3 and continuing for approximately 6 months. Patients also receive mycophenolate
mofetil IV every 8 hours on days -3 to 5 and then orally on days 6-30.

After completion of study treatment, patients are followed at 6 months and then annually
thereafter.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Diagnosis of advanced hematologic malignancy or other disease not curable by
conventional chemotherapy, including any of the following:

- Acute myeloid leukemia in complete remission (CR)* (as defined by hematologic
recovery, < 5% blasts in the bone marrow by morphology, and a cellularity of >
15%), meeting one of the following criteria:

- In first complete remission (CR1) AND has high-risk disease as evidenced by
any of the following:

- Preceding myelodysplastic syndromes (MDS)

- High-risk cytogenetics (e.g., monosomy 5 or 7, or as defined by
referring institution treatment protocol)

- Required > 2 courses of therapy to obtain CR

- Erythroblastic or megakaryocytic leukemia

- In second CR (CR2) or beyond

- Acute lymphoblastic leukemia in CR* (as defined by hematologic recovery, < 5%
blasts in the bone marrow by morphology, and a cellularity of > 15%), meeting
one of the following criteria:

- In CR1 AND has high-risk disease as evidenced by any of the following:

- t(9;22), t(1;19), t(4;11), or other MLL rearrangements

- Hyplodiploid

- Required > 1 course of therapy to obtain CR

- Beyond CR2

- Chronic myelogenous leukemia (CML)

- All types are allowed (except refractory blast crisis CML)

- Patients in chronic phase CML must have failed or been intolerant to prior
imatinib mesylate (Gleevec) or other tyrosine kinase inhibitors

- MDS

- Any subtype allowed (including refractory anemia [RA])

- Severe pancytopenia or complex cytogenetics

- Blasts must be < 5% (if blasts are ≥ 5%, pre-transplant induction therapy
is required to reduce blast count to < 5%)

- Large cell lymphoma, Hodgkin lymphoma, or multiple myeloma, meeting one of the
following criteria:

- Chemotherapy-sensitive disease that has failed prior therapy

- Patients with large cell lymphoma or Hodgkin lymphoma must not have
progressive disease during salvage therapy (stable disease allowed
provided it is non-bulky)

- Ineligible for an autologous stem cell transplant

- Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone
B-cell lymphoma, or follicular lymphoma that has progressed after ≥ 2 prior
therapies

- Patients with bulky disease should be considered for debulking chemotherapy
prior to transplant

- Patients with refractory disease are eligible provided disease is non-bulky
AND an estimated tumor doubling time is ≥ 1 month

- Lymphoplasmacytic lymphoma, mantle cell lymphoma, or prolymphocytic leukemia

- Chemotherapy-sensitive disease that was previously treated with initial
therapy

- Patients with mantle cell lymphoma must not have progressive disease
during salvage therapy (stable disease allowed provided it is
non-bulky)

- Mycosis fungoides and Sezary syndrome

- Bone marrow failure syndromes, except for Fanconi anemia

- Myeloproliferative syndromes NOTE: *Patients for whom adequate marrow/biopsy
specimens can not be obtained to determine remission status by morphologic
assessment must have fulfilled criteria of remission (< 5% blasts by flow
cytometry and recovery of peripheral blood counts with no circulating blasts)

- Ineligible for autologous stem cell transplant due to any of the following:

- Prior autologous stem cell transplant

- Inadequate autologous stem cell harvest

- Inability to withstand a myeloablative preparative regimen

- Clinically aggressive/high-risk disease

- No evidence of progressive disease by imaging modalities or biopsy (persistent PET
scan activity allowed provided there are no CT scan changes indicating progression)

- Acute leukemia that is refractory, persistent, or relapsed (defined as > 5% blasts in
normocellular bone marrow) allowed provided patient was rendered aplastic either by
induction chemotherapy or radioimmunoconjugated monoclonal antibody therapy

- Patients with stable disease are eligible provided the largest residual nodal mass is
approximately < 5 cm (largest residual mass must represent a 50% reduction and be
approximately < 7.5 cm for patients who have responded to prior therapy)

- No active CNS malignancy

- Umbilical cord blood (UCB) donor available

- UCB graft matched at 4/6 HLA-A, -B, and -DRB1 antigens with the recipient

- May include 0-2 antigen mismatches at the A, B, or DRB1 loci

- Unit selection based on cryopreserved nucleated cell dose and HLA-A, -B,
and -DRB1 using intermediate resolution A, B antigen and DRB1 allele typing

- If 2 UCB units are required to reach the target cell dose, each unit must be a
3/6 HLA-A, -B, and -DRB1 antigen match to each other, as well as a 4/6 antigen
match to the recipient

- No 5-6/6 HLA-A, -B, and -DRB1 matched sibling donor available

PATIENT CHARACTERISTICS:

- Karnofsky performance status (PS) 60-100% OR Lansky PS 50-100%

- Creatinine ≤ 2.0 mg/dL (adults) OR creatinine clearance > 40 mL/min (pediatrics)

- Adult patients with a creatinine > 1.2 mg/dL or a history of renal dysfunction
must have an estimated creatinine clearance of > 40 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- LVEF ≥ 35%

- DLCO > 30% predicted

- No requirement for O_2

- No decompensated congestive heart failure

- No uncontrolled arrhythmia

- None of the following liver diseases or conditions:

- Fulminant liver failure

- Cirrhosis with evidence of portal hypertension or bridging fibrosis

- Alcoholic hepatitis

- Esophageal varices

- History of bleeding esophageal varices, hepatic encephalopathy, or correctable
hepatic synthetic dysfunction as evidenced by prolongation of the prothrombin
time

- Ascites related to portal hypertension

- Bacterial or fungal abscess

- Biliary obstruction

- Chronic viral hepatitis with total serum bilirubin > 3 mg/dL

- Symptomatic biliary disease

- Recent mold infection (e.g., Aspergillus) allowed provided patient received ≥ 30 days
of appropriate treatment AND infection is controlled and cleared by Infectious
Disease

- No evidence of HIV infection or known HIV-positive serology

- No uncontrolled viral or bacterial infection

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- At least 3 months since prior myeloablative stem cell transplantation

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Probability of survival at 1 year

Outcome Time Frame:

1 year

Safety Issue:

No

Principal Investigator

Colleen Delaney, MD, MSC

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center

Authority:

United States: Federal Government

Study ID:

2012.00

NCT ID:

NCT00719849

Start Date:

November 2005

Completion Date:

December 2009

Related Keywords:

  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Diseases
  • chronic myelogenous leukemia
  • acute lymphoblastic leukemia
  • acute myeloid leukemia
  • atypical chronic myeloid leukemia
  • chronic myelomonocytic leukemia
  • anaplastic large cell lymphoma
  • splenic marginal zone lymphoma
  • nodal marginal zone B-cell lymphoma
  • recurrent adult Hodgkin lymphoma
  • recurrent adult diffuse large cell lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • recurrent childhood large cell lymphoma
  • recurrent mycosis fungoides/Sezary syndrome
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent mantle cell lymphoma
  • recurrent marginal zone lymphoma
  • recurrent small lymphocytic lymphoma
  • recurrent/refractory childhood Hodgkin lymphoma
  • childhood diffuse large cell lymphoma
  • childhood immunoblastic large cell lymphoma
  • refractory multiple myeloma
  • de novo myelodysplastic syndromes
  • previously treated myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • myelodysplastic/myeloproliferative disease
  • childhood myelodysplastic syndromes
  • recurrent childhood anaplastic large cell lymphoma
  • refractory anemia
  • refractory anemia with excess blasts
  • refractory anemia with ringed sideroblasts
  • refractory cytopenia with multilineage dysplasia
  • stage III adult diffuse large cell lymphoma
  • stage IV adult diffuse large cell lymphoma
  • stage III adult immunoblastic large cell lymphoma
  • stage IV adult immunoblastic large cell lymphoma
  • stage III childhood anaplastic large cell lymphoma
  • stage III childhood large cell lymphoma
  • stage IV childhood anaplastic large cell lymphoma
  • stage IV childhood large cell lymphoma
  • stage III adult Hodgkin lymphoma
  • stage III childhood Hodgkin lymphoma
  • stage IV adult Hodgkin lymphoma
  • stage IV childhood Hodgkin lymphoma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • stage III chronic lymphocytic leukemia
  • stage IV chronic lymphocytic leukemia
  • stage III small lymphocytic lymphoma
  • stage IV small lymphocytic lymphoma
  • stage III marginal zone lymphoma
  • stage IV marginal zone 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
  • Waldenstrom macroglobulinemia
  • stage III mantle cell lymphoma
  • stage IV mantle cell lymphoma
  • stage III mycosis fungoides/Sezary syndrome
  • stage IV mycosis fungoides/Sezary syndrome
  • juvenile myelomonocytic leukemia
  • chronic eosinophilic leukemia
  • chronic idiopathic myelofibrosis
  • chronic neutrophilic leukemia
  • essential thrombocythemia
  • polycythemia vera
  • Neoplasms
  • Leukemia
  • Lymphoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Lymphoma, Large-Cell, Immunoblastic
  • Lymphoma, Large-Cell, Anaplastic
  • Myelodysplastic-Myeloproliferative Diseases

Name

Location

Fred Hutchinson Cancer Research CenterSeattle, Washington  98109