- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00719888
Umbilical Cord Blood Transplant, Cyclophosphamide, Fludarabine, and Total-Body Irradiation in Treating Patients With Hematologic Disease
Transplantation of Umbilical Cord Blood for Patients With Hematological Diseases With Cyclophosphamide/Fludarabine/Total Body Irradiation or Cyclophosphamide/Fludarabine/Thiotepa/Total Body Irradiation Myeloablative Preparative Regimen
Study Overview
Status
Conditions
- Follicular Lymphoma
- Acute Myeloid Leukemia
- Myelofibrosis
- Burkitt Lymphoma
- Acute Lymphoblastic Leukemia
- Lymphoblastic Lymphoma
- Mantle Cell Lymphoma
- Marginal Zone Lymphoma
- Chronic Lymphocytic Leukemia
- Lymphoplasmacytic Lymphoma
- Non-Hodgkin Lymphoma
- Myelodysplastic Syndrome
- Plasma Cell Myeloma
- Prolymphocytic Leukemia
- Small Lymphocytic Lymphoma
- Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
- Chronic Myelogenous Leukemia, BCR-ABL1 Positive
- Acute Biphenotypic Leukemia
- Refractory Anemia
Intervention / Treatment
Detailed Description
OUTLINE: Patients are assigned to 1 of 2 arms.
ARM I: Patients receive myeloablative conditioning comprising fludarabine intravenously (IV) over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 and -6, and undergo high-dose TBI twice daily (BID) on days -4 to -1. Patients then undergo single- or double-unit UCBT on day 0.
ARM II: Patients receive myeloablative conditioning comprising fludarabine IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 2-4 hours on days -5 and -4, and middle-intensity TBI once daily (QD) on days -2 and -1. Patients then undergo single- or double-unit UCBT on day 0.
Patients receive GVHD prophylaxis comprising cyclosporine IV over 1 hour every 8 or 12 hours, then cyclosporine orally (PO) (if tolerated), on days -3 to 100 with taper on day 101. Patients also receive mycophenolate mofetil IV every 8 hours on days 0 to 7 and then PO (if tolerated) three times daily (TID) on days 8-30. Mycophenolate mofetil is tapered to BID on day 30 or 7 days after engraftment if there is no acute GVHD, and then tapered over 2-3 weeks beginning on day 45 (or 15 days after engraftment if engraftment occurred > day 30) after engraftment if there continues to be no evidence of acute GVHD.
After completion of study treatment, patients are followed up at 6 months, 1 year, and 2 years.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Colorado
-
Aurora, Colorado, United States, 80045
- University of Colorado Hospital
-
-
Washington
-
Seattle, Washington, United States, 98109
- Fred Hutch/University of Washington Cancer Consortium
-
Seattle, Washington, United States, 98101
- VA Puget Sound Health Care System
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
GRAFT CRITERIA:
- UCB units will be selected according to current umbilical cord blood graft selection algorithm; one or 2 UCB units may be used to achieve the required cell dose
- The UCB graft is matched at 4-6 human leukocyte antigen (HLA)-A, B, DRB1 antigens with the recipient; this may include 0-2 antigen mismatches at the A or B or DRB1 loci; unit selection based on cryopreserved nucleated cell dose and HLA-A,B, 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 4-6 antigen match to the recipient
Age and Disease Criteria:
- High-dose TBI regimen: 6 months to =< 45 years
- Middle-intensity TBI regimen: 6 months to =< 65 years
- Conditioning regimen selection should be based on the underlying disease, presence of minimum residual disease (MRD), age, co-morbidities, and attending physician
Acute myeloid leukemia, including biphenotypic acute leukemia or mixed-lineage leukemia:
- All patients must be in complete remission (CR) as defined by hematologic recovery and < 5% blasts by morphology/flow cytometry in a representative bone marrow sample with cellularity >= 15% for age; patients who do not have high-risk features (for example preceding myelodysplastic syndrome [MDS], high-risk cytogenetics, >= 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia or >= CR2) must be discussed with the principal investigator (PI) prior to enrollment and at the Patient Care Conference or equivalent group such as the pediatric leukemia board as an alternative
- Patients in whom 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 PI prior to enrollment; patients persistently aplastic for greater than one month since completing last chemotherapy are also eligible with PI approval
- Very high risk pediatric/young adult patients with acute myeloid leukemia (AML): Patients =< 25 years, however, are eligible with (M2 marrow) with =< 25% blasts in marrow after having failed one or more cycles of chemotherapy; this group of patients will be analyzed separately
Acute lymphoblastic leukemia, including biphenotypic acute leukemia or mixed-lineage leukemia:
- All patients must be in CR as defined by < 5% blasts by morphology; flow cytometry in a representative bone marrow sample with cellularity >= 15% for age; patients who do not have high-risk disease (high risk CR1, greater than one cycle to obtain CR or >= CR2) must be discussed with the PI prior to enrollment and at the Patient Care Conference or equivalent group such as the pediatric leukemia board as an alternative
- Patients in whom 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 Ann Dahlberg prior to enrollment; patients persistently aplastic for greater than one month since completing last chemotherapy are also eligible with PI approval
- Chronic myelogenous leukemia excluding refractory blast crisis; to be eligible in first chronic phase (CP1) patient must have failed or be intolerant to imatinib mesylate
- Advanced myelofibrosis
- Myelodysplasia (MDS) International Prognostic Scoring System (IPSS) intermediate (Int)-2 or high risk (i.e., refractory anemia with excess blasts [RAEB], RAEB in transformation [RAEBt]) or refractory anemia with severe pancytopenia or high risk cytogenetics; blasts must be < 10% by a representative bone marrow aspirate morphology
- Lymphoblastic lymphoma, Burkitt's lymphoma, and other high-grade non-Hodgkin lymphoma (NHL) after initial therapy if stage III/IV in first partial response (PR1) or after progression if stage I/II < 1 year; stage III/IV patients are eligible after progression in CR/PR
- Chronic lymphocytic leukemia /small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, lymphoplasmacytic lymphoma or follicular lymphoma that have progressed after at least two different prior therapies; patients with bulky disease (nodal mass greater than 5 cm) should be considered for debulking chemotherapy before transplant; these patients must be presented at primary care center (PCC) prior to enrollment, given potential competing eligibility on autotransplant protocols
- Mantle-cell lymphoma, prolymphocytic leukemia: Eligible after initial therapy in >= CR1 or >= PR1
Large cell NHL > CR2/> second partial response (PR2):
- Patients in CR2/PR2 with initial short remission (< 6 months) are eligible
- These patients must be presented at PCC prior to enrollment, given potential competing eligibility on autotransplant protocols
- Multiple myeloma beyond PR2: Patients with chromosome 13 abnormalities, first response lasting less than 6 months, or beta-2 microglobulin > 3 mg/L, may be considered for this protocol after initial therapy
- Performance status score: Karnofsky (for adults) >= 70% or Eastern Cooperative Oncology Group (ECOG) 0-1 or Lansky (for children) >= 50%
- Creatinine < 2.0 mg/dL (for adults) or creatinine clearance > 60 ml/min (for children)
- 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 > 3 mg/dL, and symptomatic biliary disease will be excluded
- Diffusion capacity for carbon monoxide corrected (DLCOcorr) > 50% normal or a pediatric patient who is unable to perform pulmonary function tests (PFTs) but has adequate pulmonary function
- Left ventricular ejection fraction > 45% or shortening fraction > 26%
Exclusion Criteria:
- Uncontrolled viral or bacterial infection at the time of study enrollment
- Active or recent (prior 6 month) invasive fungal infection without interdisciplinary (ID) consult and approval
- History of human immunodeficiency virus (HIV) infection
- Pregnant or breastfeeding
- Chemotherapy refractory large cell and high grade NHL (i.e., progressive disease after > 2 salvage regimens)
- Patients with history of prior myeloablative transplant containing full dose TBI (greater than 8 gray [Gy]) will not be eligible for Regimen A; however, they may still enroll on Regimen B if they otherwise meet inclusion and exclusion criteria
- Any prior myeloablative transplant within the last 6 months
- Patients >= 45 years: comorbidity score of 5 or higher
- Patients who have received Y-90 ibritumomab (Zevalin) or I-131 tostumomab (Bexxar), as part of their salvage therapy are not eligible for Regimen A
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (myeloablative UCBT)
Patients receive myeloablative conditioning comprising fludarabine IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 and -6, and undergo high-dose TBI BID on days -4 to -1. Patients then undergo single- or double-unit UCBT on day 0. Patients receive GVHD prophylaxis comprising cyclosporine IV over 1 hour every 8 or 12 hours, then cyclosporine PO (if tolerated), on days -3 to 100 with taper on day 101. Patients also receive mycophenolate mofetil IV every 8 hours on days 0 to 7 and then PO (if tolerated) TID on days 8-30. Mycophenolate mofetil is tapered to BID on day 30 or 7 days after engraftment if there is no acute GVHD, and then tapered over 2-3 weeks beginning on day 45 (or 15 days after engraftment if engraftment occurred > day 30) after engraftment if there continues to be no evidence of acute GVHD. |
Correlative studies
Given IV
Other Names:
Given IV
Other Names:
Given IV and PO
Other Names:
Undergo double-unit UCBT
Given IV and PO
Other Names:
Undergo high-dose or moderate-intensity TBI
Other Names:
Undergo UCBT
Other Names:
|
Experimental: Arm II (myeloablative UCBT)
Patients receive myeloablative conditioning comprising fludarabine IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 2-4 hours on days -5 and -4, and middle-intensity TBI QD on days -2 and -1. Patients then undergo single- or double-unit UCBT on day 0. Patients receive GVHD prophylaxis comprising cyclosporine IV over 1 hour every 8 or 12 hours, then cyclosporine PO (if tolerated), on days -3 to 100 with taper on day 101. Patients also receive mycophenolate mofetil IV every 8 hours on days 0 to 7 and then PO (if tolerated) TID on days 8-30. Mycophenolate mofetil is tapered to BID on day 30 or 7 days after engraftment if there is no acute GVHD, and then tapered over 2-3 weeks beginning on day 45 (or 15 days after engraftment if engraftment occurred > day 30) after engraftment if there continues to be no evidence of acute GVHD. |
Correlative studies
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV and PO
Other Names:
Undergo double-unit UCBT
Given IV and PO
Other Names:
Undergo high-dose or moderate-intensity TBI
Other Names:
Undergo UCBT
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival
Time Frame: 1 year
|
A non-statistical comparison with historical controls will be made.
Monitoring will take place separately for the single and double umbilical cord blood transplantation (UCBT) cohorts.
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in level of chimerism at multiple time points
Time Frame: Baseline up to 2 years
|
Cumulative incidence estimates will be used.
|
Baseline up to 2 years
|
Incidence of transplant-related mortality
Time Frame: At 6 months
|
Monitoring will take place separately for the single and double UCBT cohorts.
|
At 6 months
|
Incidence of neutrophil engraftment
Time Frame: At day 42
|
Monitoring will take place separately for the single and double UCBT cohorts.
|
At day 42
|
Incidence of platelet recovery
Time Frame: At 6 months
|
Monitoring will take place separately for the single and double UCBT cohorts.
|
At 6 months
|
Incidence of grade II-IV and III-IV acute graft-versus-host disease (GVHD)
Time Frame: At day 100
|
Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level.
Monitoring will take place separately for the single and double UCBT cohorts.
|
At day 100
|
Incidence of chronic GVHD
Time Frame: Up to 2 years
|
Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level.
|
Up to 2 years
|
Incidence of clinically significant infections
Time Frame: Up to 2 years
|
Monitoring will take place separately for the single and double UCBT cohorts.
|
Up to 2 years
|
Incidence of relapse
Time Frame: Up to 2 years
|
Cumulative incidence estimates will be used to summarize the time-to-event outcomes.
|
Up to 2 years
|
Progression-free survival
Time Frame: Up to 2 years
|
A non-statistical comparison with historical controls will be made.
Cumulative incidence estimates will be used to summarize the time-to-event outcomes.
Monitoring will take place separately for the single and double UCBT cohorts.
|
Up to 2 years
|
Single unit umbilical cord blood (UCB) transplants with historical controls
Time Frame: Up to 2 years
|
Single unit UCB transplants with historical controls will be compared.
|
Up to 2 years
|
Single unit UCB transplants with double unit UCB transplants
Time Frame: Up to 2 years
|
Single unit UCB transplants with double unit UCB transplants will be compared.
|
Up to 2 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Ann E. Dahlberg, Fred Hutch/University of Washington Cancer Consortium
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Virus Diseases
- Infections
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Disease Attributes
- Bone Marrow Diseases
- Hematologic Diseases
- Hemorrhagic Disorders
- Myeloproliferative Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- DNA Virus Infections
- Anemia
- Tumor Virus Infections
- Neoplasms, Plasma Cell
- Leukemia, Lymphoid
- Epstein-Barr Virus Infections
- Herpesviridae Infections
- Leukemia, B-Cell
- Lymphoma, B-Cell
- Chronic Disease
- Lymphoma
- Myelodysplastic Syndromes
- Multiple Myeloma
- Leukemia
- Leukemia, Myeloid
- Burkitt Lymphoma
- Lymphoma, Mantle-Cell
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Waldenstrom Macroglobulinemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Leukemia, Myeloid, Chronic-Phase
- Leukemia, Prolymphocytic
- Leukemia, Biphenotypic, Acute
- Anemia, Refractory
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Dermatologic Agents
- Anti-Bacterial Agents
- Antibiotics, Antineoplastic
- Antifungal Agents
- Antitubercular Agents
- Antibiotics, Antitubercular
- Calcineurin Inhibitors
- Cyclophosphamide
- Fludarabine
- Mycophenolic Acid
- Thiotepa
- Cyclosporine
- Cyclosporins
Other Study ID Numbers
- 2010.00
- 2010 (Fred Hutch/University of Washington Cancer Consortium)
- NCI-2010-00190 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- RG2807002 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Follicular Lymphoma
-
Joseph TuscanoNational Cancer Institute (NCI); Genentech, Inc.; Pharmacyclics LLC.RecruitingAnn Arbor Stage II Follicular Lymphoma | Ann Arbor Stage III Follicular Lymphoma | Ann Arbor Stage IV Follicular Lymphoma | Grade 1 Follicular Lymphoma | Grade 2 Follicular Lymphoma | Grade 3a Follicular LymphomaUnited States
-
National Cancer Institute (NCI)RecruitingRecurrent Follicular Lymphoma | Refractory Follicular Lymphoma | Grade 1 Follicular Lymphoma | Grade 2 Follicular Lymphoma | Grade 3a Follicular LymphomaUnited States
-
Memorial Sloan Kettering Cancer CenterFox Chase Cancer Center; Pharmacyclics LLC.TerminatedFollicular Lymphoma | Follicular Lymphoma, Grade 1 | Follicular Lymphoma, Grade 2 | Follicular Lymphoma Grade IIIaUnited States
-
National Cancer Institute (NCI)TerminatedStage 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 LymphomaUnited States
-
Robert LowskyNational Cancer Institute (NCI); Janssen, LP; The Leukemia and Lymphoma Society; Rising Tide FoundationCompletedMantle Cell Lymphoma | Marginal Zone Lymphoma | Recurrent Follicular Lymphoma | Refractory Follicular Lymphoma | Grade 1 Follicular Lymphoma | Grade 2 Follicular Lymphoma | Grade 3a Follicular LymphomaUnited States
-
Olivia Newton-John Cancer Research InstituteBristol-Myers Squibb; Barwon Health; Austin Health; Eastern Health; Fiona Stanley... and other collaboratorsRecruitingFollicular Lymphoma Stage II | Follicular Lymphoma Stage III | Follicular Lymphoma Stage IVAustralia
-
Fondazione Italiana Linfomi ONLUSCompletedFollicular Lymphoma, Grade 1 | Follicular Lymphoma, Grade 2 | Follicular Lymphoma Grade 3AItaly
-
Massachusetts General HospitalTG TherapeuticsActive, not recruitingLymphoma | Follicular Lymphoma | Marginal Zone Lymphoma | Follicular Lymphoma, Grade 1 | Follicular Lymphoma Grade IIIa | Marginal Zone B Cell Lymphoma | Follicular Lymphoma Grade 2United States
-
Epizyme, Inc.RecruitingFollicular Lymphoma | Relapsed/Refractory Follicular Lymphoma | Refractory Follicular LymphomaUnited States, China, Spain, France, Taiwan, United Kingdom, Australia, Korea, Republic of, Canada, Italy, Hungary, Poland, Belgium, Germany
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingGrade 3a Follicular Lymphoma | Ann Arbor Stage III Grade 1 Follicular Lymphoma | Ann Arbor Stage III Grade 2 Follicular Lymphoma | Ann Arbor Stage IV Grade 1 Follicular Lymphoma | Ann Arbor Stage IV Grade 2 Follicular Lymphoma | Ann Arbor Stage III Grade 3 Follicular Lymphoma | Ann Arbor Stage...United States
Clinical Trials on Laboratory Biomarker Analysis
-
Children's Oncology GroupNational Cancer Institute (NCI)Completed
-
ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)CompletedProstate Cancer
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Active, not recruitingLeukemia | Acute Lymphoblastic Leukemia | Acute Promyelocytic LeukemiaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedUntreated Adult Acute Lymphoblastic Leukemia | Untreated Childhood Acute Lymphoblastic LeukemiaUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Lymphoblastic Leukemia in Remission | Recurrent Childhood Acute Lymphoblastic LeukemiaUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)CompletedLung CancerUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
Children's Oncology GroupNational Cancer Institute (NCI)WithdrawnClear Cell Renal Cell Carcinoma | Rhabdoid Tumor of the Kidney | Congenital Mesoblastic Nephroma | Childhood Kidney NeoplasmUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)WithdrawnBreast Carcinoma | BRCA1 Mutation Carrier | BRCA2 Mutation CarrierUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedWilms Tumor and Other Childhood Kidney TumorsUnited States