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Transplantation of Umbilical Cord Blood in Patients With Hematological Malignancies Using a Treosulfan Based Preparative Regimen


Phase 2
N/A
65 Years
Open (Enrolling)
Both
Accelerated Phase Chronic Myelogenous Leukemia, Adult Acute Lymphoblastic Leukemia in Remission, Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Blastic Phase Chronic Myelogenous Leukemia, Childhood Acute Lymphoblastic Leukemia in Remission, Childhood Acute Myeloid Leukemia in Remission, Childhood Chronic Myelogenous Leukemia, Childhood Myelodysplastic Syndromes, Chronic Phase Chronic Myelogenous Leukemia, de Novo Myelodysplastic Syndromes, Meningeal Chronic Myelogenous Leukemia, Myelodysplastic Syndrome With Isolated Del(5q), Previously Treated Myelodysplastic Syndromes, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia, Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Refractory Anemia, Refractory Anemia With Excess Blasts, Refractory Anemia With Excess Blasts in Transformation, Refractory Anemia With Ringed Sideroblasts, Refractory Cytopenia With Multilineage Dysplasia, Relapsing Chronic Myelogenous Leukemia, Secondary Myelodysplastic Syndromes, Untreated Adult Acute Lymphoblastic Leukemia, Untreated Adult Acute Myeloid Leukemia, Untreated Childhood Acute Lymphoblastic Leukemia, Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

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Trial Information

Transplantation of Umbilical Cord Blood in Patients With Hematological Malignancies Using a Treosulfan Based Preparative Regimen


PRIMARY OBJECTIVES:

I. Combined incidence of primary graft failure/rejection and secondary graft failure in Arm
1 and Arm 2.

II. Day 200 non-relapse mortality in Arm 1 and Arm 2.

SECONDARY OBJECTIVES:

I. Incidence of platelet engraftment by six months.

II. Incidence of grade II-IV and III-IV acute graft-versus-host disease (GVHD) at day 100
and one year.

III. Incidence of one year chronic GVHD.

IV. Incidence of clinically significant infections at 6 months, 1 year, 2 years.

V. Probability of one and two year survival.

VI. Incidence of one and two year relapse or disease progression.

VII. Kinetics of immune reconstitution, with both functional and quantitative assays (Fred
Hutchinson Cancer Research Center [FHCRC] only).

VIII. Examination of possible immunologic factors leading to emergence of a dominant unit
(FHCRC only).

OUTLINE:

ARM I (low risk for graft failure): Patients receive a conditioning regimen comprising
fludarabine phosphate intravenously (IV) over 1 hour once daily on days -6 to -2 and
treosulfan IV over 120 minutes on days - 6 to -4. Patients undergo TBI on day -1. Patients
then undergo donor UCBT on day 0. Patients receive GVHD prophylaxis comprising cyclosporine
IV or orally (PO) 2-3 times daily on days -3 to 100, followed by a taper in the absence of
GVHD. Patients also receive mycophenolate mofetil IV 3 times daily on days 0 to 40, followed
by a taper in the absence of GVHD.

ARM II (high risk for graft failure): Patients receive a conditioning regimen, TBI, donor
UCBT, GVHD prophylaxis, and mycophenolate mofetil as in arm I.

After completion of the study treatment, patients are followed up periodically.


Inclusion Criteria:



- Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL): Must have < 20%
morphologic marrow blasts in an evaluable marrow sample (> 25% of normal cellularity
for age) collected less than one month prior to start of conditioning; patients in
which adequate marrow/biopsy specimens cannot be obtained to determine remission
status by morphologic assessment, but have fulfilled criteria of remission by flow
cytometry, recovery of peripheral blood counts with no circulating blasts, and/or
normal cytogenetics (if applicable) may still be eligible; reasonable attempts must
be made to obtain an adequate specimen for morphologic assessment, including possible
repeat procedures; these patients must be discussed with the Principal Investigator
prior to enrollment; patients persistently aplastic for greater than one month since
completing last chemotherapy are also eligible

- Myelodysplastic syndrome (MDS): Any 2001 World Health Organization (WHO)
classification subtype; refractory anemia with excess blasts (RAEB)-2 patients may
proceed directly to transplant but may also be considered for induction chemotherapy
before transplant; patients with >= 20% morphologic marrow blasts require induction
therapy to reduce morphologic marrow blasts below 5% before transplant

- Chronic myelogenous leukemia: All types, except refractory blast crisis; chronic
phase patients must have failed or been intolerant to Gleevec or other tyrosine
kinase inhibitors

- Patients =< 50 must have performance status score: Karnofsky (for adults) >= 70;
Lansky (for children) score >= 50

- Patients > 50 must have Karnofsky performance score >= 70 and comorbidity index < 5

- Adequate cardiac function defined as absence of decompensated congestive heart
failure or uncontrolled arrhythmia AND left ventricular ejection fraction >= 35% OR
fractional shortening > 22%

- Adequate hepatic function; patients with clinical or laboratory evidence of liver
disease will be evaluated for the cause of liver disease, its clinical severity in
terms of liver function, histology, and the degree of portal hypertension; patients
with fulminant liver failure, cirrhosis with evidence of portal hypertension or
bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding
esophageal varices, hepatic encephalopathy, or correctable hepatic synthetic
dysfunction 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 > 3mg/dL, and symptomatic biliary disease will
be excluded

- Adequate renal function defined as creatinine =< 2.0 mg/dl (adults) or creatinine
clearance > 40 ml/min (pediatrics); all adults with a creatinine > 1.2 or a history
of renal dysfunction must have estimated creatinine clearance > 40 ml/min

- If recent mold infection, e.g., Aspergillus, must be cleared by infectious disease to
proceed

- Second hematopoietic cell transplant: must be >= 3 months after prior myeloablative
transplant

Exclusion Criteria:

- Patients =< 65 years with an available 5-6/6 human leukocyte antigen (HLA)-A, B, DRB1
matched sibling donor

- Pregnancy or breastfeeding

- Evidence of human immunodeficiency virus (HIV) infection or known HIV positive
serology

- Uncontrolled viral or bacterial infection at the time of study enrollment

- Active or recent (prior 6 month) invasive fungal infection without ID consult and
approval

- Central nervous system (CNS) leukemic involvement not clearing with intrathecal
chemotherapy and/or cranial radiation prior to initiation of conditioning (day -6)

- AML in first complete response (CR1) with favorable prognostic cytogenetics (t8;21,
t15;17, inv16) and low risk MDS (International Prognostic Scoring System [IPSS] score
0)

- Impaired pulmonary function as evidenced by oxygen partial pressure (pO2) < 70 mm Hg
and diffusing capacity of the lung for carbon monoxide (DLCO) corrected < 70% or pO2
< 80 mm Hg and DLCO corrected < 60%; or receiving supplementary continuous oxygen

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Incidence of graft failure/rejection

Outcome Description:

For both arms we will accept a graft failure rate of 5%. Arm 1 will be terminated if graft failure rates exceed 10% after maximum dose escalation. Arm 2 will be terminated if graft failure rates exceed 15% after maximum dose escalation.

Outcome Time Frame:

By day 42

Safety Issue:

No

Principal Investigator

Colleen Delaney

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Food and Drug Administration

Study ID:

2275.00

NCT ID:

NCT00796068

Start Date:

October 2008

Completion Date:

Related Keywords:

  • Accelerated Phase Chronic Myelogenous Leukemia
  • Adult Acute Lymphoblastic Leukemia in Remission
  • Adult Acute Myeloid Leukemia in Remission
  • Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
  • Adult Acute Myeloid Leukemia With Del(5q)
  • Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
  • Blastic Phase Chronic Myelogenous Leukemia
  • Childhood Acute Lymphoblastic Leukemia in Remission
  • Childhood Acute Myeloid Leukemia in Remission
  • Childhood Chronic Myelogenous Leukemia
  • Childhood Myelodysplastic Syndromes
  • Chronic Phase Chronic Myelogenous Leukemia
  • de Novo Myelodysplastic Syndromes
  • Meningeal Chronic Myelogenous Leukemia
  • Myelodysplastic Syndrome With Isolated Del(5q)
  • Previously Treated Myelodysplastic Syndromes
  • Recurrent Adult Acute Lymphoblastic Leukemia
  • Recurrent Adult Acute Myeloid Leukemia
  • Recurrent Childhood Acute Lymphoblastic Leukemia
  • Recurrent Childhood Acute Myeloid Leukemia
  • Refractory Anemia
  • Refractory Anemia With Excess Blasts
  • Refractory Anemia With Excess Blasts in Transformation
  • Refractory Anemia With Ringed Sideroblasts
  • Refractory Cytopenia With Multilineage Dysplasia
  • Relapsing Chronic Myelogenous Leukemia
  • Secondary Myelodysplastic Syndromes
  • Untreated Adult Acute Lymphoblastic Leukemia
  • Untreated Adult Acute Myeloid Leukemia
  • Untreated Childhood Acute Lymphoblastic Leukemia
  • Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies
  • Congenital Abnormalities
  • Anemia
  • Anemia, Refractory
  • Anemia, Refractory, with Excess of Blasts
  • Blast Crisis
  • Neoplasms
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myeloid, Accelerated Phase
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Leukemia, Myeloid, Chronic-Phase
  • Myelodysplastic Syndromes
  • Preleukemia
  • Anemia, Aplastic

Name

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle, Washington  98109
Oregon Health and Science University Portland, Oregon  97201
University of Colorado Cancer Center - Anschutz Cancer Pavilion Aurora, Colorado  80045