NCT00963872 · REGISTRY CONDITION SEARCH

Donor Umbilical Cord Blood Transplant After Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation in Treating Patients With High-Risk Hematologic Cancer

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1, PHASE2
Status at capture: TERMINATED
Registry last update: 2017-12-28

RATIONALE: Giving low doses of chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). PURPOSE: This phase I trial is studying the safety of donor umbilical cord blood transplant after fludarabine phosphate, cyclophosphamide, and total-body irradiation in treating patients with high-risk hematologic cancer (now closed). The Phase II part of this trial is studying whether priming one of two UCB units with C3a facilitates engraftment of the treated unit.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number of Patients With the Complement 3a (C3a) Unit Predominating

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outcome · POSTED

Neutrophil Engraftment

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outcome · POSTED

Donor Chimerism in Blood

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outcome · POSTED

Incidence of Grades II-IV Graft-vs-host Disease

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outcome · POSTED

Non-Relapse Mortality

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outcome · POSTED

Overall Survival

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outcome · POSTED

Bone Marrow Chimerism

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outcome · POSTED

Chronic Graft-Versus-Host Disease

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outcome · POSTED

Relapse of Disease

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outcome · POSTED

Disease Progression

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outcome · POSTED

Platelet Recovery

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outcome · POSTED

Donor Chimerism in Blood

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outcome · POSTED

Incidence of Grades III-IV Graft-vs-host Disease

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outcome · POSTED

Non-relapse Mortality

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outcome · POSTED

Overall Survival at Day 720

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outcome · POSTED

Relapse of Disease

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outcome · POSTED

Disease Progression

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outcome · POSTED

Donor Chimerism

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outcome · POSTED

Donor Chimerism

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outcome · POSTED

Donor Chimerism

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Disease Criteria * Acute Leukemias: Must be in remission by morphology (\<5% blasts). Note cytogenetic relapse or persistent disease without morphologic relapse is acceptable. Also a small percentage of blasts that is equivocal between marrow regeneration vs. early relapse are acceptable provided there are no associated cytogenetic markers consistent with relapse. (See exclusion criteria for more detailed definition) * Acute myeloid leukemia: high risk CR1 (as evidenced by preceding myelodysplastic syndrome (MDS), high risk cytogenetics such as those associated with MDS or complex karyotype, \> 2 cycles to obtain complete remission (CR) or erythroblastic and megakaryocytic); second or greater CR. * Acute lymphoblastic leukemia/lymphoma: high risk CR1 as evidenced by high risk cytogenetics (e.g. t(9;22, t(1;19), t(4;11), other MLL rearrangements) or \> 1 cycle to obtain CR; second or greater CR. * Burkitt's lymphoma in CR2 or subsequent CR * Natural Killer cell malignancies * Myeloproliferative syndromes/diseases: Chronic myelogenous leukemia (CML) in chronic or accelerated phase but patients must have failed or been intolerant to Imatinib mesylate. EXCLUDED: CML in refractory blast crisis, myelofibrosis, polycythemia vera, and essential thrombocytosis. * Myelodysplastic Syndrome: any subtype including refractory anemia (RA) if severe pancytopenia, high risk complex cytogenetics or International Prognostic Scoring System (IPSS) ≥ intermediate-2 (Int-2). Blasts must be less than 5%. If 5% or more requires therapy pre-transplant to reduce blast count to ≤5%. Patients who receive single agent 5-azacytidine, decitabine or immunomodulating drugs are eligible. * Large-cell lymphoma, Hodgkin's lymphoma and multiple myeloma: patients with chemotherapy sensitive disease that has failed or who are ineligible for an autologous transplant. Patients are eligible for umbilical cord blood (UCB) transplantation if there is no evidence of progressive disease by imaging modalities and/or biopsy. Persistent PET activity, though possibly related to lymphoma, IS NOT an exclusion criterion in the absence of computated tomography (CT) changes in size indicating progression. Large-cell and Hodgkin's lymphoma that is progressive on salvage therapy is NOT eligible. Patients with stable disease are eligible for transplantation if the largest residual nodal mass is \< 5 cm (approximately). For patients who have responded to preceding therapy, the largest residual mass must represent a 50% reduction and be \< 7.5 cm (approximately). * Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, follicular lymphoma which have progressed after at least two prior therapies. Patients with bulky disease should be considered for debulking chemotherapy before transplant. Patients with refractory disease are eligible, unless has bulky disease and an estimated tumor doubling time of less than one month. Patients with stable disease are eligible for transplantation if the largest residual nodal mass is \< 5 cm (approximately). For patients who have responded to preceding therapy, the largest residual mass must represent a 50% reduction and be \< 7.5 cm (approximately). * Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligible after initial therapy if chemotherapy sensitive. Mantle-cell lymphoma that is progressive on salvage therapy is NOT eligible. Patients with stable disease are eligible for transplantation if the largest residual nodal mass is \< 5 cm (approximately). For patients who have responded to preceding therapy, the largest residual mass must represent a 50% reduction and be \< 7.5 cm (approximately). * Umbilical Cord Blood Graft Selection - Two UCB units will be compose the graft, and each unit must be a 4-6 HLA-A, B, DRB1 antigen match to each other, as well as a 4-6 antigen match to the recipient. The combined cryopreserved nucleated cell dose of the 2 units must be ≥ 3 X 10\^7/kg with each unit having a minimum cell dose of 1.5 X 10\^7/kg. UCB units will be selected according to a common umbilical cord blood graft selection algorithm * Performance Status - adequate performance status defined as Karnofsky score ≥ 60 * Age 18 to 70 years of age; patients ≥ 70 but ≤ 75 years are eligible if the co-morbidity score is ≤ 2 * Organ Function * Cardiac: Left ventricular ejection fraction \> 35%; absence of decompensated congestive heart failure; absence of uncontrolled arrhythmia * Pulmonary: DLCO \> 30% of predicted; absence of O2 requirements * Hepatic: ALT, AST, alkaline phosphatase and bilirubin \< 5 x upper limit of normal * Renal: Creatinine ≤ 2 mg/dl (patients with a creatinine \> 1.2 or history of renal dysfunction must have calculated glomerular filtration rate (GFR) \> 40 mL/min/1.73m2) * If recent mold infection e.g. Aspergillus - must have minimum of 30 days of appropriate treatment before transplant and infection controlled and be cleared by Infectious Disease. * The following conditions must be met: * If prior myeloablative autologous transplant, must be \> 3 months but ≤ 12 months from transplant OR have received at least 2 cycles of multi-agent or highly immunosuppressive chemotherapy (i.e. induction for acute leukemia) within the 3 months preceding this study. OR * If neither prior myeloablative autologous transplant ≤ 12 months from transplant nor have received at least 2 cycles of multi-agent or highly immunosuppressive chemotherapy (i.e. induction for acute leukemia) within the 3 months preceding this study, patients are eligible as long as they receive equine anti-thymocyte globulin as part of the conditioning regimen. Exclusion Criteria: * Patients who have an available, medically suitable, 5-6/6 HLA-A, B, DRB1 matched sibling donor * Patients who are eligible for autologous transplantation * Prior allogeneic transplant * Acquired or inherited bone marrow failure syndromes such as aplastic anemia and Fanconi anemia * Pregnant or breast feeding * Evidence of HIV infection or known HIV positive serology * Current uncontrolled serious infection * Active central nervous system malignancy
healthy Volunteers: false
maximum Age: 75 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the smaller cell dose following preparation regimen and radiation.
intervention Names
Drug: cyclophosphamide
Drug: fludarabine phosphate
Radiation: Total body irradiation
Biological: Umbilical cord blood unit with C3a fragment
Biological: Unmanipulated UCB Unit
label
Complement Fragment 3A - Small Cell Dose
type
EXPERIMENTAL
description
Patients who received complement fragment 3a (C3a) priming of the UCB unit with the larger cell dose.
intervention Names
Drug: cyclophosphamide
Drug: fludarabine phosphate
Radiation: Total body irradiation
Biological: Umbilical cord blood unit with C3a fragment
Biological: Unmanipulated UCB Unit
label
Complement Fragment A - Larger Cell Dose
type
EXPERIMENTAL

interventions

arm Group Labels
Complement Fragment 3A - Small Cell Dose
Complement Fragment A - Larger Cell Dose
description
50 mg/kg intravenously (IV) over 2 hours on Day -6.
name
cyclophosphamide
other Names
Cytoxan
type
DRUG
arm Group Labels
Complement Fragment 3A - Small Cell Dose
Complement Fragment A - Larger Cell Dose
description
40 mg/m\^2 over 1 hour on Days -6 through -2.
name
fludarabine phosphate
other Names
Fludara
type
DRUG
arm Group Labels
Complement Fragment 3A - Small Cell Dose
Complement Fragment A - Larger Cell Dose
description
200 cGy on Day -1
name
Total body irradiation
type
RADIATION
arm Group Labels
Complement Fragment 3A - Small Cell Dose
Complement Fragment A - Larger Cell Dose
description
On Day 0, the C3a primed UCB unit will be infused intravenously SECOND, within 30 minutes of the completion of the infusion of the unmanipulated UCB unit, through a central line without in-line filtration in a manner identical to the unmanipulated UCB unit.
name
Umbilical cord blood unit with C3a fragment
type
BIOLOGICAL
arm Group Labels
Complement Fragment 3A - Small Cell Dose
Complement Fragment A - Larger Cell Dose
description
On Day 0, the unmanipulated UCB unit will be infused FIRST through a central line without in-line filtration per institutional guidelines.
name
Unmanipulated UCB Unit
type
BIOLOGICAL

Study design

allocation

RANDOMIZED

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 31
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Efficacy of the pre-incubation of one of two umbilical cord blood (UCB) units with C3a as part of a unrelated donor double UCB nonmyeloablative transplantation in patients with high-risk hematological malignancies.
measure
Number of Patients With the Complement 3a (C3a) Unit Predominating
time Frame
Day 180

secondary Outcomes

description
Achieving 500 neutrophils/uL by day 42.
measure
Neutrophil Engraftment
time Frame
Day 42
description
Percentage of donor DNA present in the peripheral blood
measure
Donor Chimerism in Blood
time Frame
Day 28
description
Development of graft-versus-host disease through day 100.
measure
Incidence of Grades II-IV Graft-vs-host Disease
time Frame
Day 0 through Day 100
description
Deaths not due to relapse.
measure
Non-Relapse Mortality
time Frame
Day 180
description
Survival (alive) from transplantation to last follow-up.
measure
Overall Survival
time Frame
Day 360
description
Percentage of donor DNA in the bone marrow.
measure
Bone Marrow Chimerism
time Frame
Day 21
description
Patients who developed chronic graft-versus-host disease.
measure
Chronic Graft-Versus-Host Disease
time Frame
Day 360
description
Patients who developed disease relapse after transplantation.
measure
Relapse of Disease
time Frame
Day 360
description
Patients who developed disease progression after transplantation.
measure
Disease Progression
time Frame
Day 360
description
Number of patients with \>20,000 platelets/uL by day 180
measure
Platelet Recovery
time Frame
Day 180
description
Percentage of donor DNA present in the peripheral blood
measure
Donor Chimerism in Blood
time Frame
Day 60
description
Development of graft-versus-host disease by day 100.
measure
Incidence of Grades III-IV Graft-vs-host Disease
time Frame
0 to 100 days

Full study description

brief Summary: RATIONALE: Giving low doses of chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). PURPOSE: This phase I trial is studying the safety of donor umbilical cord blood transplant after fludarabine phosphate, cyclophosphamide, and total-body irradiation in treating patients with high-risk hematologic cancer (now closed). The Phase II part of this trial is studying whether priming one of two UCB units with C3a facilitates engraftment of the treated unit.
detailed Description: OUTLINE: * Nonmyeloablative preparative regimen: Patients receive fludarabine phosphate IV over 1 hour on days -6 to -2 and cyclophosphamide IV over 2 hours on day -6. Patients then undergo total-body irradiation on day -1. Some patients also receive anti-thymocyte globulin IV every 12 hours on days -6, -5, and -4. * Umbilical cord blood (UCB) transplantation: Patients undergo unmanipulated UCB transplantation followed by complement 3a fragment primed UCB transplantation on day 0. Treatment for graft-vs-host disease prophylaxis is also given. After completion of study therapy, patients are followed up periodically for up to 2 years.

Source references

Source notices and limitations

Discovery and provenance

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Preserved source evidence · Not medical advice