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Pilot Study Of Multiple Umbilical Cord Blood Unit Transplantation Following Non-Myeloablative Conditioning In Patients With Hematologic Disorders Or Severe Aplastic Anemia


Phase 1
N/A
N/A
Not Enrolling
Both
Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases

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Trial Information

Pilot Study Of Multiple Umbilical Cord Blood Unit Transplantation Following Non-Myeloablative Conditioning In Patients With Hematologic Disorders Or Severe Aplastic Anemia


OBJECTIVES:

- Determine the incidence and severity of acute toxicity in patients with hematologic
malignancies or severe aplastic anemia treated with a non-myeloablative conditioning
regimen followed by umbilical cord blood transplantation.

- Determine the incidence and severity of acute and chronic graft-versus-host-disease in
patients treated with this regimen.

- Determine the incidence of relapse, disease-free survival, and overall survival of
patients treated with this regimen.

- Determine the survival rate at 100 days post-transplantation in patients treated with
this regimen.

- Determine the incidence of regimen-related complications (infection, hepatic
veno-occlusive disease, and interstitial pneumonitis) in patients treated with this
regimen.

- Determine the incidence of primary and secondary graft failure in patients treated with
this regimen.

- Determine the rates and kinetics of donor-derived lymphoid, myeloid, neutrophil, RBC,
and platelet engraftment in patients treated with this regimen.

OUTLINE: Patients receive a non-myeloablative conditioning regimen comprising fludarabine IV
over 30 minutes on days -8 to -4, cyclophosphamide IV over 2 hours on days -3 to -2, and
anti-thymocyte globulin (ATG) IV over at least 4 hours on days -2 to -1. Patients unable to
tolerate ATG may receive methylprednisolone IV over 1 hour on days -3 to -1.

Patients undergo multiple unit umbilical cord blood transplantation on days 0-1. Patients
receive filgrastim (G-CSF) subcutaneously beginning on day 7 and continuing until blood
counts recover.

Patients are followed monthly for 6 months; at 9, 12, 14, 16, 18, and 24 months; and then
annually thereafter.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study within 2 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- One of the following histologically confirmed diagnoses:

- Acquired severe aplastic anemia

- Meets at least 2 of the following criteria:

- Granulocyte count less than 500/mm^3

- Platelet count less than 20,000/mm^3

- Absolute reticulocyte count less than 20,000/mm^3 (after correction
for hematocrit)

- Unresponsive to OR recurrent disease after prior treatment with
anti-thymocyte globulin and/or cyclosporine

- Acute myeloid leukemia (AML), meeting 1 of the following criteria:

- Failed induction therapy

- In first complete remission (CR) with any of the following high-risk
features:

- Stem cell or biphenotype classification (M0)

- Erythroleukemia (M6)

- Acute megakaryocytic leukemia (M7)

- Cytogenetic markers indicative of poor prognosis

- t(15;17) translocation and failed first-line induction therapy OR
there is molecular evidence of persistent disease

- t(8;21) and inv(16) translocations and failed first-line induction
therapy

- In early relapse*

- In second or subsequent remission

- Recurrent disease after prior autologous stem cell transplantation (SCT)
NOTE: *No refractory relapse

- Acute lymphoblastic leukemia, meeting 1 of the following criteria:

- In early relapse*

- In second or subsequent remission

- In first CR with the following high-risk features:

- t(4;11) or t(9;22) translocation

- Hyperleukocytosis (initial WBC greater than 30,000/mm^3)

- Failed to achieve CR by day 28 of standard induction therapy

- Recurrent disease after prior autologous SCT NOTE: *No refractory relapse

- Chronic myelogenous leukemia

- Chronic or accelerated phase that has failed medical management

- Blastic phase allowed after reinduction chemotherapy induces chronic phase

- Myelodysplastic syndromes meeting 1 of the following criteria:

- Refractory to medical management

- Presence of cytogenetic abnormalities predictive of transformation to acute
leukemia, including the following:

= 5q- = 7q-

- Monosomy 7 and trisomy 8

- Evidence of evolution to AML (e.g., refractory anemia with excess blasts [RAEB], or
RAEB in transformation)

- Chronic lymphocytic leukemia

- Refractory to treatment including fludarabine-based therapy

- Recurrent disease after prior autologous SCT

- Multiple myeloma

- Recurrent disease after prior autologous SCT

- Beyond first CR or failed induction therapy

- Disease is sensitive to pretransplantation cytoreduction

- Hodgkin's lymphoma

- Beyond first CR or failed induction therapy

- Disease is sensitive to pretransplantation cytoreduction

- Non-Hodgkin's lymphoma (NHL)

- Recurrent disease after prior autologous SCT

- Beyond first CR or failed induction therapy

- Disease is sensitive to pretransplantation cytoreduction

- Mantle zone NHL allowed after induction therapy

- Myeloproliferative disorders

- Refractory to medical management

- Allografting required unless grade 3 or greater myelofibrosis by bone
marrow biopsy

- No HLA-matched sibling donor available

- Ineligible for a myeloablative conditioning regimen due to advanced
age (over 55), extensive prior therapy, and/or other comorbidities

- If under age 55, must meet at least 1 of the following criteria:

- Received extensive prior therapy

- Organ toxicity or infection precluding eligibility for allogeneic
transplantation with full ablation conditioning

- Availability of 2-5 umbilical cord blood units that are at least a 4/6 HLA
match

- No active CNS disease

- No primary or grade 3 or 4 myelofibrosis

PATIENT CHARACTERISTICS:

Age

- Any age

Performance status

- Karnofsky 70-100% (for patients 16 years of age and older)

- Lansky 50-100% (for patients under 16 years of age)

Life expectancy

- At least 3 months

Hematopoietic

- See Disease Characteristics

Hepatic

- ALT/AST less than 4 times normal

- Bilirubin less than 2.0 mg/dL (unless due to hepatic infiltration by primary
malignancy)

Renal

- Creatinine clearance greater than 40 mL/min

Cardiovascular

- Shortening fraction or ejection fraction greater than 40% of normal value for age by
echocardiogram or radionuclide scan

Pulmonary

- FVC and FEV_1 greater than 60% of predicted

- DLCO greater than 60% of predicted (adult patients)

- Clearance by pulmonologist required if patient cannot perform pulmonary function
tests

Other

- Not pregnant or nursing

- No uncontrolled active infection (viral, bacterial, or fungal)

- HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

- See Disease Characteristics

- More than 3 months since prior autologous stem cell transplantation

Chemotherapy

- See Disease Characteristics

- At least 4 weeks since prior chemotherapy

Endocrine therapy

- Not specified

Radiotherapy

- Not specified

Surgery

- Not specified

Other

- Recovered from prior therapy

- No other concurrent investigational agents that would preclude study participation or
increase risk to patient

- Investigational diagnostic procedures allowed

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Event-free survival by disease assessment

Outcome Time Frame:

at 28 and 100 days and then at 6, 9, 12, 18, and 24 months

Safety Issue:

No

Principal Investigator

Brenda Cooper, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

CWRU6Y01

NCT ID:

NCT00054236

Start Date:

May 2002

Completion Date:

March 2011

Related Keywords:

  • Chronic Myeloproliferative Disorders
  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Diseases
  • refractory anemia with excess blasts in transformation
  • refractory anemia with excess blasts
  • adult acute myeloid leukemia in remission
  • childhood acute myeloid leukemia in remission
  • recurrent adult acute myeloid leukemia
  • recurrent childhood acute myeloid leukemia
  • adult erythroleukemia (M6a)
  • childhood acute erythroleukemia (M6)
  • adult acute minimally differentiated myeloid leukemia (M0)
  • childhood acute minimally differentiated myeloid leukemia (M0)
  • adult acute megakaryoblastic leukemia (M7)
  • childhood acute megakaryocytic leukemia (M7)
  • adult acute lymphoblastic leukemia in remission
  • childhood acute lymphoblastic leukemia in remission
  • recurrent adult acute lymphoblastic leukemia
  • recurrent childhood acute lymphoblastic leukemia
  • accelerated phase chronic myelogenous leukemia
  • chronic phase chronic myelogenous leukemia
  • previously treated myelodysplastic syndromes
  • refractory chronic lymphocytic leukemia
  • stage I multiple myeloma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • recurrent/refractory childhood Hodgkin lymphoma
  • polycythemia vera
  • primary myelofibrosis
  • essential thrombocythemia
  • refractory multiple myeloma
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent adult diffuse large cell lymphoma
  • recurrent adult diffuse mixed cell lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • recurrent adult Burkitt lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • recurrent adult lymphoblastic lymphoma
  • recurrent mantle cell lymphoma
  • recurrent childhood large cell lymphoma
  • recurrent childhood lymphoblastic lymphoma
  • recurrent childhood small noncleaved cell lymphoma
  • childhood diffuse large cell lymphoma
  • childhood immunoblastic large cell lymphoma
  • Burkitt lymphoma
  • anaplastic large cell lymphoma
  • recurrent adult Hodgkin lymphoma
  • childhood chronic myelogenous leukemia
  • chronic eosinophilic leukemia
  • chronic neutrophilic leukemia
  • myelodysplastic/myeloproliferative disease, unclassifiable
  • atypical chronic myeloid leukemia
  • recurrent marginal zone lymphoma
  • recurrent 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 t(8;21)(q22;q22)
  • adult acute myeloid leukemia with t(16;16)(p13;q22)
  • adult acute myeloid leukemia with inv(16)(p13;q22)
  • adult acute myeloid leukemia with 11q23 (MLL) abnormalities
  • adult acute myeloid leukemia with t(15;17)(q22;q12)
  • childhood myelodysplastic syndromes
  • Anemia
  • Anemia, Aplastic
  • Neoplasms
  • Leukemia
  • Lymphoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Lymphoma, Large-Cell, Immunoblastic
  • Myelodysplastic-Myeloproliferative Diseases

Name

Location

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer CenterCleveland, Ohio  44106-5065