CompletedNCT00547196Updated Jun 14, 2024Results posted

AlloHCT From Matched Unrelated Donors in Pts w/ Advanced Hematologic Malignancies & Disorders

An interventional study of filgrastim and Busulfan in Leukemia, Lymphoma and Myelodysplastic Syndromes, sponsored by City of Hope Medical Center. Completed at 2 sites in United States. Open to participants aged 0 Years to 120 Years. Per ClinicalTrials.gov, last updated 2024-06-14.

Sponsored by City of Hope Medical Center · Not applicable, Interventional, and Treatment

From the registry’s dates

Registered 2 years 2 months after the study started (first participant enrolled Aug 2005, registered Oct 2007).

Phase: Not applicable
Study type: Interventional
Enrollment: 10
Allocation: Non-randomized
Ages: 0 Years to 120 Years
Sex: All

Study summary

RATIONALE: Giving chemotherapy with or without total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening.

PURPOSE: This clinical trial is studying how well four different chemotherapy regimens given with or without total-body irradiation before umbilical cord blood transplant work in treating patients with relapsed or refractory hematologic cancer.

Read the detailed description

OBJECTIVES:

Primary

To determine the survival at day 100 of patients with relapsed, refractory, or poor-risk hematological malignancies treated with four different preparative regimens followed by allogeneic hematopoietic stem cell transplantation (HSCT) using two unrelated umbilical cord blood (UCB) units.

Secondary

To determine the incidence and timing of neutrophil engraftment in patients treated with these regimens.
To determine the incidence and timing of platelet engraftment in patients treated with these regimens.
To determine the incidence and severity of acute and chronic graft-versus-host-disease (GVHD) in patients treated with these regimens.
To determine the survival at day 180 in patients treated with these regimens.
To determine the disease-free survival in patients treated with these regimens.
To determine the incidence of primary and secondary engraftment failure in patients treated with these regimens.
To determine the incidence of transplantation-related complications (e.g., infection, veno-occlusive disease of the liver, or organ toxicity) in these patients.
To determine the incidence of post-transplantation-related lymphoproliferative disease, secondary myelodysplastic syndromes, or other secondary malignancies in these patients.
To determine the incidence of relapse in patients treated with these regimens.
To determine post-transplantation chimerism in patients treated with these regimens.
To determine immune reconstitution in patients treated with these regimens.

OUTLINE: This is a multicenter study.

Preparative regimens: Patients are assigned to 1 of 4 preparative regimens.
- Regimen 1 (for patients \< 50 years of age and no contraindication to fractionated total-body irradiation (FTBI): Patients undergo FTBI 2-3 times a day on days -9 to -6 for a total of 11 fractions. Patients also receive cyclophosphamide IV over 2 hours on days -5 and -4 and fludarabine phosphate IV on days -5 to -2.
- Regimen 2 (for patients \< 50 years of age and unable to tolerate FTBI due to prior dose-limiting radiotherapy or significant cardiotoxicity): Patients receive a test dose of busulfan on day -10 and then dose adjusted busulfan IV 3-4 times daily on days -9 to -6, melphalan IV on days -5 and -4, and fludarabine phosphate IV on days -5 to -2.
- Regimen 3* (for patients unable to tolerate regimen 1 or 2; no age exclusion): Patients receive fludarabine phosphate IV on days -8 to -4 and cyclophosphamide IV over 2 hours on day -3 and undergo TBI (single dose) on day -2.
- Regimen 4* (for patients unable to tolerate regimen 1 or 2): Patients receive fludarabine phosphate IV on days -7 to -3 and melphalan IV on day -2.

NOTE: *Treating physician decides the choice between regimen 3 and 4

Umbilical cord blood (UCB) transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover.
Graft-versus-host-disease prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated).

After completion of study therapy, patients are followed periodically.

Conditions studied

Leukemia
Lymphoma
Myelodysplastic Syndromes

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Keywords

refractory chronic lymphocytic leukemia
adult acute myeloid leukemia in remission
recurrent adult acute myeloid leukemia
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute lymphoblastic leukemia in remission
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult grade III lymphomatoid granulomatosis
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
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
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
relapsing chronic myelogenous leukemia
recurrent cutaneous T-cell non-Hodgkin lymphoma
secondary acute myeloid leukemia

In context

Lymphoma

5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.

This study's enrollment of 10 is below the median of 40 across 4,509 interventional studies indexed under Lymphoma.

Browse Lymphoma studies →

Lead sponsor

City of Hope Medical Center is the lead sponsor of 670 studies on the registry; 181 are open to participants now.

Of its 30 completed or terminated interventional studies of FDA-regulated products, 12 (40%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 0 Years to 120 Years
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

DISEASE CHARACTERISTICS:

Histologically confirmed hematological or lymphatic malignancy, including any of the following:
- Acute myeloid leukemia
  - Relapsed or primary refractory disease with \< 10% blasts on peripheral blood smear
  - In first remission with poor risk factors and molecular prognosis [i.e., AML with -5, -7, t(6;9), tri8, -11] (preparative regimen 3 or 4)
- Acute lymphocytic leukemia
  - In second complete remission or higher OR in first remission with poor risk factors, including any of the following (preparative regimen 1 or 2):
    - BCR/ABL by fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction
    - t(9;22)(q34;q11) detected by cytogenetics
    - Chromosomes \< 44 by cytogenetics
    - DNA index \< 0.81 by flow cytometry
    - Any rearrangement of chromosome 11 that results in disruption of MLL gene (11q23) by cytogenetics and SER
  - In first remission with poor risk factors and molecular prognosis [ALL with Philadelphia chromosome-positive t(9;22), t(4;22), (q34;q11)] (preparative regimen 3 or 4)
- Chronic myelogenous leukemia
  - In accelerated phase or greater (preparative regimen 1 or 2)
  - In accelerated or second chronic phase (preparative regimen 3 or 4)
- Myelodysplastic syndromes
  - With deletion of chromosome 7 or short arm of chromosome 5 (preparative regimen 1 or 2)
  - In high and high-intermediate risk categories (preparative regimen 3 or 4)
- Non-Hodgkin lymphoma in relapse with marrow involvement
- Refractory chronic lymphocytic leukemia
Patients deemed ineligible for conventional high-dose chemotherapy programs (i.e., regimens 1 or 2) due to any of the following concurrent medical conditions may be eligible for regimens 3 or 4 at the discretion of the treating physician and principal investigator (preparative regimen 3 or 4):
- LVEF \< 50% and > 40%
- FEV1, FVC, or DLCO \< 50%
- Bilirubin > 3 mg/dL
- Creatinine > 2 mg/dL
Two partially HLA-matched umbilical cord blood (UCB) units available
- HLA-matched minimally at 4 of 6 HLA-A, HLA-B, and -DRB1 loci with the patient
  - DRB1 matched by high resolution DNA typing
  - HLA-A and HLA-B matched by low resolution at the "serological match" level
- Two pooled units with a nucleated cell number > 2.5 x 10\^7/kg
No available HLA-identical sibling or 1 antigen-mismatched related donor
No available HLA-matched unrelated bone marrow donor

PATIENT CHARACTERISTICS:

See Disease Characteristics
Karnofsky performance status (PS) 60-100% OR Lansky PS 60-100% OR Zubrod PS 0-1
Physiological age 60 or less (at any chronological age)
Weight > 50 kg
Creatinine normal for age OR creatinine clearance by 24-hour urine collection or glomerular filtration rate > 60 mL/min
Bilirubin ≤ 1.5 mg/dL
LVEF ≥ 50%
DLCO ≥ 60% of predicted
No HIV-1 infection
No active uncontrolled infection
Not pregnant
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Recovered from prior intensive chemotherapy

Study design

Phase: Not applicable
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 10 participants (actual)

Study arms

Experimental
Regimen I (FTBI, Cyclophosphamide, Fludarabine)
Patients undergo FTBI 2-3 times a day on days -9 to -6 for a total of 11 fractions. Patients also receive cyclophosphamide IV over 2 hours on days -5 and -4 and fludarabine phosphate IV on days -5 to -2. UCB transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover. GVHD prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated).
Biological: filgrastim · Drug: Cyclophosphamide · Drug: Cyclosporine · Drug: Fludarabine phosphate · Drug: Mycophenolate Mofetil · Procedure: allogeneic hematopoietic stem cell transplantation · Procedure: umbilical cord blood transplantation · Radiation: Fractionated total body irradiation
Experimental
Regimen II (Busulfan, Fludarabine, Melphalan)
Patients receive a test dose of busulfan on day -10 and then dose adjusted busulfan IV 3-4 times daily on days -9 to -6, melphalan IV on days -5 and -4, and fludarabine phosphate IV on days -5 to -2. UCB transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover. GVHD prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated).
Biological: filgrastim · Drug: Busulfan · Drug: Cyclosporine · Drug: Fludarabine phosphate · Drug: Melphalan · Drug: Mycophenolate Mofetil · Procedure: allogeneic hematopoietic stem cell transplantation · Procedure: umbilical cord blood transplantation
Experimental
Regimen III (TBI, Cyclophosphamide, Fludarabine)
Patients receive fludarabine phosphate IV on days -8 to -4 and cyclophosphamide IV over 2 hours on day -3 and undergo TBI (single dose) on day -2. UCB transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover. GVHD prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated).
Biological: filgrastim · Drug: Cyclophosphamide · Drug: Cyclosporine · Drug: Fludarabine phosphate · Drug: Mycophenolate Mofetil · Procedure: allogeneic hematopoietic stem cell transplantation · Procedure: umbilical cord blood transplantation · Radiation: total-body irradiation
Experimental
Regimen IV (Fludarabine, Melphalan)
Patients receive fludarabine phosphate IV on days -7 to -3 and melphalan IV on day -2. UCB transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover. GVHD prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated).
Biological: filgrastim · Drug: Cyclosporine · Drug: Fludarabine phosphate · Drug: Melphalan · Drug: Mycophenolate Mofetil · Procedure: allogeneic hematopoietic stem cell transplantation · Procedure: umbilical cord blood transplantation

Interventions

Biologicalfilgrastim
DrugBusulfan
Also known as: Busilvex
DrugCyclophosphamide
Also known as: CTX
DrugCyclosporine
Also known as: CsA
DrugFludarabine phosphate
Also known as: Fludara
DrugMelphalan
Also known as: Alkeran
DrugMycophenolate Mofetil
Also known as: MMF
Procedureallogeneic hematopoietic stem cell transplantation
Also known as: AlloHCT
Procedureumbilical cord blood transplantation
Radiationtotal-body irradiation
Also known as: TBI
RadiationFractionated total body irradiation
Also known as: FTBI

What researchers measure

Primary outcomes

Survival Rate at Day 100 After Allogeneic Transplant From Umbilical Cord Blood (UCB)
Number of surviving patients at Day 100 post-transplant divided by number of patients undergone transplantation.
Time frame: From transplant to Day 100 post-transplant

Secondary outcomes

Survival Rate at Day 180 After Allogeneic Transplant From Umbilical Cord Blood (UCB)
Number of surviving patients at Day 180 post-transplant divided by number of patients undergone transplantation.
Time frame: From transplant up to Day 180 post-transplant

Results

Posted Apr 13, 2023

Participant flow

Participant flow — Overall Study
Milestone	Regimen I (FTBI, Cyclophosphamide, Fludarabine)	Regimen III (TBI, Cyclophosphamide, Fludarabine)	Regimen IV (Fludarabine, Melphalan)	Unassigned
Started	5	1	2	2
Completed	5	1	2	2
Not completed	0	0	0	0

Outcome measures

PrimarySurvival Rate at Day 100 After Allogeneic Transplant From Umbilical Cord Blood (UCB)

Number of surviving patients at Day 100 post-transplant divided by number of patients undergone transplantation.

Time frame:: From transplant to Day 100 post-transplant
Reported as:: Number · percentage of surviving patients

Survival Rate at Day 100 After Allogeneic Transplant From Umbilical Cord Blood (UCB)
percentage of surviving patients	Regimen I (FTBI, Cyclophosphamide, Fludarabine)	Regimen II (Busulfan, Fludarabine, Melphalan)	Regimen III (TBI, Cyclophosphamide, Fludarabine)	Regimen IV (Fludarabine, Melphalan)
Survival Rate at Day 100 After Allogeneic Transplant From Umbilical Cord Blood (UCB)	100	—	100	100

SecondarySurvival Rate at Day 180 After Allogeneic Transplant From Umbilical Cord Blood (UCB)

Number of surviving patients at Day 180 post-transplant divided by number of patients undergone transplantation.

Time frame:: From transplant up to Day 180 post-transplant
Reported as:: Number · percentage of surviving patients

Survival Rate at Day 180 After Allogeneic Transplant From Umbilical Cord Blood (UCB)
percentage of surviving patients	Regimen I (FTBI, Cyclophosphamide, Fludarabine)	Regimen II (Busulfan, Fludarabine, Melphalan)	Regimen III (TBI, Cyclophosphamide, Fludarabine)	Regimen IV (Fludarabine, Melphalan)
Survival Rate at Day 180 After Allogeneic Transplant From Umbilical Cord Blood (UCB)	60	—	100	50

Adverse events

Collected over Adverse Events monitored/assessed up to 100 days post-transplant. All-Cause Mortality monitored/assessed up to 9 years post-transplant.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Regimen I (FTBI, Cyclophosphamide, Fludarabine)	3/5 (60%)	2/5 (40%)	3/5 (60%)
Regimen II (Busulfan, Fludarabine, Melphalan)	—	—	—
Regimen III (TBI, Cyclophosphamide, Fludarabine)	1/1 (100%)	1/1 (100%)	1/1 (100%)
Regimen IV (Fludarabine, Melphalan)	2/2 (100%)	1/2 (50%)	1/2 (50%)

Most frequent serious events

Most frequent serious events
Event	Regimen I (FTBI, Cyclophosphamide, Fludarabine)	Regimen II (Busulfan, Fludarabine, Melphalan)	Regimen III (TBI, Cyclophosphamide, Fludarabine)	Regimen IV (Fludarabine, Melphalan)
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L)Infections and infestations	1/5	—	1/1	0/2
Infection, Bacterial (COH)Infections and infestations	0/5	—	1/1	0/2
Hemorrhage, GUBlood and lymphatic system disorders	0/5	—	0/1	1/2
CreatinineInvestigations	0/5	—	0/1	1/2
ALT, SGPT (serum glutamic pyruvic transaminase)Investigations	1/5	—	0/1	0/2
AST, SGOT(serum glutamic oxaloacetic transaminase)Investigations	1/5	—	0/1	0/2
Dyspnea (shortness of breath)Respiratory, thoracic and mediastinal disorders	1/5	—	0/1	0/2

Most frequent other events

Showing 10 of 62

Most frequent other events
Event	Regimen I (FTBI, Cyclophosphamide, Fludarabine)	Regimen II (Busulfan, Fludarabine, Melphalan)	Regimen III (TBI, Cyclophosphamide, Fludarabine)	Regimen IV (Fludarabine, Melphalan)
Hemorrhage, GUBlood and lymphatic system disorders	1/5	—	1/1	0/2
HypertensionCardiac disorders	3/5	—	1/1	1/2
HypotensionCardiac disorders	1/5	—	1/1	1/2
Cushingoid appearance (e.g., moon face, buffalo hump, centripetal obesity, cutaneous striae)Endocrine disorders	0/5	—	1/1	0/2
DiarrheaGastrointestinal disorders	2/5	—	1/1	1/2
NauseaGastrointestinal disorders	3/5	—	1/1	1/2
VomitingGastrointestinal disorders	3/5	—	1/1	1/2
Fatigue (asthenia, lethargy, malaise)General disorders	0/5	—	1/1	0/2
PainGeneral disorders	3/5	—	1/1	1/2
Weight gainGeneral disorders	2/5	—	1/1	1/2

Baseline characteristics

No subject in Regimen II.

Age, Continuous
Age, Continuous(years)	Regimen I (FTBI, Cyclophosphamide, Fludarabine)	Regimen II (Busulfan, Fludarabine, Melphalan)	Regimen III (TBI, Cyclophosphamide, Fludarabine)	Regimen IV (Fludarabine, Melphalan)	Unassigned	Total
Median	14 (11 to 18)	—	58 (58 to 58)	35 (16 to 54)	18.5 (9 to 28)	15 (9 to 58)

Sex: Female, Male
Sex: Female, Male(Participants)	Regimen I (FTBI, Cyclophosphamide, Fludarabine)	Regimen II (Busulfan, Fludarabine, Melphalan)	Regimen III (TBI, Cyclophosphamide, Fludarabine)	Regimen IV (Fludarabine, Melphalan)	Unassigned	Total
Female	1	—	1	1	0	3
Male	4	—	0	1	2	7

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Regimen I (FTBI, Cyclophosphamide, Fludarabine)	Regimen II (Busulfan, Fludarabine, Melphalan)	Regimen III (TBI, Cyclophosphamide, Fludarabine)	Regimen IV (Fludarabine, Melphalan)	Unassigned	Total
American Indian or Alaska Native	0	—	0	0	0	0
Asian	1	—	1	0	0	2
Native Hawaiian or Other Pacific Islander	0	—	0	0	0	0
Black or African American	1	—	0	0	1	2
White	3	—	0	2	1	6
More than one race	0	—	0	0	0	0
Unknown or Not Reported	0	—	0	0	0	0

Region of Enrollment
Region of Enrollment(participants)	Regimen I (FTBI, Cyclophosphamide, Fludarabine)	Regimen II (Busulfan, Fludarabine, Melphalan)	Regimen III (TBI, Cyclophosphamide, Fludarabine)	Regimen IV (Fludarabine, Melphalan)	Unassigned	Total
United States	5	—	1	2	2	10

Study locations

2 sites

Banner Good Samaritan Medical Center
Phoenix, Arizona 85006, United States
City of Hope Medical Center
Duarte, California 91010-3000, United States

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jun 14, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00547196
Lead sponsor: City of Hope Medical Center
Collaborators: National Cancer Institute (NCI)
Responsible party: Sponsor
First posted: Oct 22, 2007
Start date: Aug 16, 2005
Primary completion: Nov 11, 2009
Completion: May 28, 2024
Results posted: Apr 13, 2023
Last update: Jun 14, 2024

Study contacts

Anna Pawlowska, MD

principal investigator · City of Hope Medical Center

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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