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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 12 December 2020
Main ID:  NCT00397813
Date of registration: 09/11/2006
Prospective Registration: Yes
Primary sponsor: Fred Hutchinson Cancer Research Center
Public title: Fludarabine Phosphate and Total Body Irradiation Followed by a Donor Peripheral Stem Cell Transplant in Treating Patients With Myelodysplastic Syndromes or Myeloproliferative Disorders
Scientific title: Low-Dose TBI Dose Escalation to Decrease Risks of Progression and Graft Rejection After Hematopoietic Cell Transplantation With Nonmyeloablative Conditioning as Treatment for Untreated Myelodysplastic Syndrome or Myeloproliferative Disorders - A Multi-Center Trial
Date of first enrolment: January 2006
Target sample size: 77
Recruitment status: Completed
URL:  https://clinicaltrials.gov/show/NCT00397813
Study type:  Interventional
Study design:  Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).  
Phase:  Phase 2
Countries of recruitment
Denmark Germany Italy United States
Contacts
Name:     Brenda Sandmaier
Address: 
Telephone:
Email:
Affiliation:  Fred Hutch/University of Washington Cancer Consortium
Key inclusion & exclusion criteria

Inclusion Criteria:

- Patients aged >= 50 and < 75 years (yrs) with CMML, or previously untreated MDS or MPD

- Patients aged < 50 yrs at high risk for regimen related toxicity using standard high
dose regimens; factors considered high risk include pre-existing conditions such as a
chronic disease affecting kidneys, liver, lungs, or heart or previous failed HCT

- An human leukocyte antigen (HLA)-identical related or an HLA-matched unrelated donor
(Fred Hutchinson Cancer Research Center [FHCRC] matching allowed will be Grade 1.0 to
2.1) is available

- Recovery from the effects of previous chemotherapy, with a minimum of 21 days from
initiation of last therapy; hydroxyurea or anagrelide may be used to manage elevated
cell counts in patients up to the time they begin therapy under this protocol

- Patients < 12 yrs of age must be discussed on a case by case basis with the primary
investigator (PI) of the protocol prior to registration

- A signed informed consent form or minor assent form

- MDS: MDS classifiable by the World Health Organization (WHO) system as RA, RARS,
refractory cytopenia with multilineage dysplasia (RCMD), RCMD and ringed sideroblasts
(RCMD-RS) or RAEB

- MDS: No previous myelosuppressive therapy; for the purpose of this protocol
myelosuppressive chemotherapy will be defined as chemotherapy given with the intent of
inducing a complete remission (e.g., standard 7+3, high dose intermittent ARA-C
[HIDAC], or Mylotarg)

- MDS: Patients must have < 10% marrow blasts; fewer than 10% marrow blasts must be
documented by marrow examination within 3 weeks of initiation of conditioning

- CMML: Patients with CMML1 who have not received myelosuppressive therapy must have <
10% marrow blasts; fewer than 10% marrow blasts must be documented by marrow
examination within 3 weeks of initiation of conditioning; OR patients with CMML who
have progressed beyond CMML1 and have received myelosuppressive chemotherapy must have
< 5% marrow blasts; fewer than 5% marrow blasts must be documented by marrow
examination within 3 weeks of initiation of conditioning

- MPD: Patients with polycythemia vera with persistent thrombotic or hemorrhagic
complications despite conventional therapy, or who have progressed to postpolycythemic
marrow fibrosis

- MPD: Patients with essential thrombocythemia with persistent thrombotic or hemorrhagic
complications despite conventional therapy, or who have progressed to myelofibrosis

- MPD: Chronic idiopathic myelofibrosis with peripheral blood cytopenias

- MPD: Patients must have < 10% marrow blasts; fewer than 10% marrow blasts must be
documented by marrow examination within 3 weeks of initiation of conditioning

- MPD: No previous myelosuppressive therapy; for the purpose of this protocol
myelosuppressive chemotherapy will be defined as chemotherapy given with the intent of
inducing a complete remission (e.g., standard 7+3, HIDAC, or Mylotarg)

- Atypical chronic myeloid leukemia (CML): Philadelphia chromosome-negative patients
with a diagnosis of atypical CML

- Atypical CML: Patients must have < 10% marrow blasts; fewer than 10% marrow blasts
must be documented by marrow examination within 3 weeks of initiation of conditioning

- Atypical CML: No previous myelosuppressive therapy; for the purpose of this protocol
myelosuppressive chemotherapy will be defined as chemotherapy given with the intent of
inducing a complete remission (e.g., standard 7+3, HIDAC, or Mylotarg)

- Paroxysmal nocturnal hemoglobinuria (PNH): Patients with the non-aplastic form of PNH
(cellular bone marrow) who have had a history of life-threatening complications of
their disease including thrombotic events, severe hemolysis or Budd Chiari syndrome
are eligible; other patients may be considered following approval at PCC and approval
by the Principal investigator

- Matched Related Donor: Related to the patient and is genotypically or phenotypically
HLA-identical

- Matched Related Donor: Donor age < 75 yrs unless cleared by institutional PI

- Matched Related Donor: Capable of giving written, informed consent

- Matched Related Donor: Donor must consent to PBSC mobilization with G-CSF and
apheresis

- Unrelated Donor: FHCRC matching allowed will be grades 1.0 to 2.1: Unrelated donors
who are prospectively:

1. Matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing;

2. Only a single allele disparity will be allowed for HLA-A, B, or C as defined by
high resolution typing

- Unrelated Donor: Patient and donor pairs homozygous at a mismatched allele in the
graft rejection vector are considered a two-allele mismatch, i.e., the patient is
A*0101 and the donor is A*0102, and this type of mismatch is not allowed

- HLA Matched Related Donor: G-CSF mobilized peripheral blood mononuclear cell (PBMC)
only will be permitted as a hematopoietic stem cell (HSC) source on this protocol

- HLA Matched Unrelated Donor: Donor must consent to PBSC mobilization with G-CSF and
apheresis; bone marrow unrelated donors are not eligible for this protocol

Exclusion Criteria:

- Organ dysfunction as defined by the following:

- Symptomatic coronary artery disease or cardiac ejection fraction < 35% (or, if
unable to obtain ejection fraction, shortening fraction of < 26%); if shortening
fraction is < 26% a cardiology consult is required with the principal
investigator (PI) having final approval of eligibility; ejection fraction is
required if age > 50 years or there is a history of anthracycline exposure or
history of cardiac disease

- Diffusing capacity of the lung for carbon monoxide (DLCO) < 35%, TLC < 35%,
forced expiratory volume (FEV)1 < 35% and/or receiving supplementary continuous
oxygen; the FHCRC PI of the study must approve of enrollment of all patients with
pulmonary nodules

- Liver function abnormalities: Patient 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, bridging fibrosis, and the degree of portal
hypertension; the patient will be excluded if he/she is found to have fulminant
liver failure, cirrhosis of the liver with evidence of portal hypertension,
alcoholic hepatitis, esophageal varices, a history of bleeding esophageal
varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction <



Age minimum: 50 Years
Age maximum: 75 Years
Gender: All
Health Condition(s) or Problem(s) studied
Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative
Chronic Myelomonocytic Leukemia
de Novo Myelodysplastic Syndrome
Essential Thrombocythemia
Myeloproliferative Neoplasm
Paroxysmal Nocturnal Hemoglobinuria
Polycythemia Vera
Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase
Primary Myelofibrosis
Refractory Anemia
Refractory Anemia With Excess Blasts
Refractory Anemia With Ring Sideroblasts
Refractory Cytopenia With Multilineage Dysplasia
Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts
Intervention(s)
Drug: Cyclosporine
Drug: Fludarabine Phosphate
Drug: Mycophenolate Mofetil
Other: Laboratory Biomarker Analysis
Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Procedure: Peripheral Blood Stem Cell Transplantation
Radiation: Total-Body Irradiation
Primary Outcome(s)
Number of Patients With HCT Failure. [Time Frame: 200 days]
Secondary Outcome(s)
Number of Patients Who Engrafted [Time Frame: 1 year]
Number of Patients Who Had Infections [Time Frame: 1 year]
Number of Patients With Progression-free Survival [Time Frame: 1 year]
Number of Patients With Relapse/Progression [Time Frame: 1 year]
Secondary ID(s)
2056.00
NCI-2010-00237
P01CA018029
P30CA015704
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Ethics review
Results
Results available: Yes
Date Posted: 24/10/2018
Date Completed:
URL: https://clinicaltrials.gov/ct2/show/results/NCT00397813
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