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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.
Last refreshed on: 12 December 2020
Main ID:  NCT01529827
Date of registration: 06/02/2012
Prospective Registration: Yes
Primary sponsor: Roswell Park Cancer Institute
Public title: Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
Scientific title: A Phase II Trial of Reduced Intensity Allogeneic Stem Cell Transplantation With Fludarabine, Melphalan and Low Dose Total Body Irradiation
Date of first enrolment: February 28, 2012
Target sample size: 94
Recruitment status: Completed
Study type:  Interventional
Study design:  Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).  
Phase:  Phase 2
Countries of recruitment
United States
Name:     George Chen
Affiliation:  Roswell Park Cancer Institute
Key inclusion & exclusion criteria

Inclusion Criteria:

- Diagnosis of a histology documented hematologic malignancy or marrow disorder


- Acquired bone marrow failure disorders include aplastic anemia, paroxysmal nocturnal
hemoglobinuria (PNH) * Primary allogeneic HSCT is appropriate for selected patients
with severe aplastic anemia; however, patients with aplastic anemia must have failed
at least one cycle of standard immunosuppressive therapy with calcineurin inhibitor
plus anti-thymocyte globulin (ATG) if a fully matched donor is available * Patients
with PNH should not be eligible for a myeloablative HSCT

- Hereditary bone marrow failure disorders include Diamond-Blackfan Anemia,
Shwachman-Diamond Syndrome, Kostmann Syndrome, congenital Amegakaryocytic
Thrombocytopenia; Fanconi Anemia or related chromosomal breakage syndrome,
Dyskeratosis Congenital are excluded from this study die to their poor
deoxyribonucleic acid (DNA) repair capacity * Fanconi anemia or related chromosomal
breakage syndrome: positive chromosome breakage analysis using diepoxybutane (DEB) or
mitomycin C if applicable * Dyskeratosis Congenita: diagnosis is supported by using
either telomerase RNA component (TERC) gene mutation in autosomal dominant
Dyskeratosis Congenita or X-linked DKC1 gene mutation

- Other non-malignant hematologic or immunologic disorders that require transplantation
* Quantitative or qualitative congenital platelet disorders (including but not limited
to congenital amegakaryocytopenia, absent-radii syndrome, Glanzmann's thrombasthenia)
* Quantitative or qualitative congenital neutrophil disorders (including but not
limited to chronic granulomatous disease, congenital neutropenia) *Congenital primary
immunodeficiency syndrome, Wiskott-Aldrich syndrome, CD40 ligand deficiency, T-cell


- Subjects must be ineligible for or unable to receive a conventional myeloablative

- Resistant or recurrent disease after at least one standard combination chemotherapy OR
first remission patients at high risk of relapse * Acute myeloid leukemia (AML)

- antecedent myelodysplastic syndrome, secondary AML, high risk cytogenetic
abnormalities or normal cytogenetics with high-risk molecular mutations (e.g.,
fms-like tyrosine kinase3-internal tandem duplication [Flt3-ITD] mutation) * Acute
lymphocytic leukemia (ALL)

- high or standard risk ALL


- Chronic phase (intolerant or unresponsive to imatinib and/or other tyrosine kinase
inhibitors), second chronic phase or accelerated phase who are ineligible for
conventional myeloablative transplantation


- Myelofibrosis (with/without splenectomy) with intermediate to high risk features

- Advanced polycythemia vera nor responding to standard therapy

- MDS with lower International Prognostic Scoring System (IPSS) score of intermediate
(Int)-2 or higher

- MDS with lower IPSS score Int-1 or less with severe clinical features such as severe
neutropenia or thrombocytopenia or high risk chromosome abnormalities such as monosomy

- Secondary MDS with any IPSS scores

- Chronic myelomonocytic leukemia


- Chronic lymphocytic leukemia (CLL), low-grade non-Hodgkin lymphoma (NHL) (recurrent or
persistent) fludarabine refractory or with less than 6 months duration or complete
remission (CR) between courses of conventional therapy

- Multiple myeloma (progressive disease after autologous stem cell transplant, tandem
allogeneic transplant after prior autologous stem cell transplant)

- Waldenstrom's macroglobulinemia (failed one standard regimen)

- High grade NHL and diffuse large B-cell lymphoma (DLBCL)

- Not eligible for conventional myeloablative HSCT OR failed autologous HSCT

- First remission lymphoblastic lymphoma, or small, non-cleaved cell lymphoma or mantle
cell lymphoma


- Received and failed front-line therapy

- Failed or were not eligible for autologous transplantation DONOR: Permissible human
leukocyte antigen (HLA) matching: related donors

- single antigen mismatch at HLA A, B, or DRB1; unrelated donors

- a single antigen mismatch at HLA A, B, or C, +/- additional single allele level
mismatch at A, B, V or DRB1

- Minimum goal for peripheral blood stem cells (PBSC) dose is 2 x 10^6 CD34+ cells/kg of
recipient weight; minimum goal for the marrow dose is 1 x 10^8 nucleated cells/kg of
recipient weight

- No serious uncontrolled psychiatric illness

- No concomitant active malignancy that would be expected to require chemotherapy within
3 years of transplant (other than non-melanoma skin cancer)

- Non-pregnant and non-nursing woman; (women or men with reproductive potential should
agree to use an effective means of birth control)

- Patients who have failed a prior autologous or allogeneic transplant are eligible;
however, at least 90 days must have elapsed between the start of this reduced
intensity conditioning regimen and the last transplant if patient had a prior
autologous or myeloablative allogeneic bone marrow transplant (BMT)

- At least 2 weeks since prior chemotherapy, radiation treatment and/or surgery

- Informed consent

DONOR: Compatibility at the four most informative HLA loci:

A, B, C and DRB1 are important for reducing the risk of GVHD and successful transplant
outcomes; the A, B, C and DRB1 loci comprise 8 possible alleles (a haplotype being
inherited from each parent); one additional locus, HLA-DQ, is also typed to ascertain
haplotypes and assist in the search for a compatible donor; however mismatching at DQ has
not been shown to be associated with adverse outcomes; high resolution molecular typing (at
the allele level) is now the standard of care for unrelated donor searches and allows
greater refinement of the search strategy

DONOR: Matched related donor:

a single antigen mismatch at A, B, or the DR transplant from a family member is associated
with a higher risk of GVHD but similar overall survival when compared to full identity at
these 3 regions; related donor/recipient pairs must be matched at 5 of 6 HLA antigens (A,
B, DRB1)

DONOR: Unrelated Donor:

When evaluating patients for unrelated donor transplant, the higher degree of matching, the
lower risk of GvHD; the A, B, C, DRB1 and DQB1 loci, compri

Age minimum: 3 Years
Age maximum: 75 Years
Gender: All
Health Condition(s) or Problem(s) studied
Accelerated Phase Chronic Myelogenous Leukemia
Adult Acute Lymphoblastic Leukemia in Remission
Adult Acute Myeloid Leukemia in Remission
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
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 Grade III Lymphomatoid Granulomatosis
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Aplastic Anemia
Burkitt Lymphoma
Childhood Acute Lymphoblastic Leukemia in Remission
Childhood Acute Myeloid Leukemia in Remission
Childhood Chronic Myelogenous Leukemia
Childhood Diffuse Large Cell Lymphoma
Childhood Grade III Lymphomatoid Granulomatosis
Childhood Immunoblastic Large Cell Lymphoma
Childhood Myelodysplastic Syndromes
Childhood Nasal Type Extranodal NK/T-cell Lymphoma
Chronic Myelomonocytic Leukemia
Chronic Phase Chronic Myelogenous Leukemia
Congenital Amegakaryocytic Thrombocytopenia
Diamond-Blackfan Anemia
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Hepatosplenic T-cell Lymphoma
Juvenile Myelomonocytic Leukemia
Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
Nodal Marginal Zone B-cell Lymphoma
Paroxysmal Nocturnal Hemoglobinuria
Peripheral T-cell Lymphoma
Polycythemia Vera
Post-transplant Lymphoproliferative Disorder
Previously Treated Myelodysplastic Syndromes
Primary Myelofibrosis
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Acute Myeloid Leukemia
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 Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Acute Myeloid Leukemia
Recurrent Childhood Anaplastic Large Cell Lymphoma
Recurrent Childhood Grade III Lymphomatoid Granulomatosis
Recurrent Childhood Large Cell Lymphoma
Recurrent Childhood Lymphoblastic Lymphoma
Recurrent Childhood Small Noncleaved Cell Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin 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 Mycosis Fungoides/Sezary Syndrome
Recurrent Small Lymphocytic Lymphoma
Recurrent/Refractory Childhood Hodgkin Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Hairy Cell Leukemia
Refractory Multiple Myeloma
Secondary Acute Myeloid Leukemia
Secondary Myelodysplastic Syndromes
Secondary Myelofibrosis
Severe Combined Immunodeficiency
Severe Congenital Neutropenia
Shwachman-Diamond Syndrome
Splenic Marginal Zone Lymphoma
T-cell Large Granular Lymphocyte Leukemia
Waldenstrom Macroglobulinemia
Wiskott-Aldrich Syndrome
Drug: fludarabine phosphate
Drug: melphalan
Drug: methotrexate
Drug: mycophenolate mofetil
Drug: tacrolimus
Other: laboratory biomarker analysis
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Radiation: total-body irradiation
Primary Outcome(s)
Transplant Related Mortality (TRM) [Time Frame: In the first 100 days from day 0 of transplant]
Secondary Outcome(s)
Clinical Response [Time Frame: In the first 100 days from day 0 of transplant]
Median Time to Neutrophil Engraftment [Time Frame: Day 100]
Progression Free Survival (PFS) at One Year [Time Frame: day of transplant until progression up to 5 years]
Secondary ID(s)
I 177110
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Ethics review
Results available: Yes
Date Posted: 02/07/2017
Date Completed:
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