Fludarabine Phosphate, Melphalan, Total-Body Irradiation, Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Bone Marrow Failure Disorders

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT00856388
• Date of registration: 04/03/2009
• Prospective Registration: No
• Primary sponsor: Roswell Park Cancer Institute
• Public title: Fludarabine Phosphate, Melphalan, Total-Body Irradiation, Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Bone Marrow Failure Disorders
• Scientific title: A Pilot Trial Of Reduced Intensity Allogeneic Stem Cell Transplantation With Fludarabine, Melphalan, And Low Dose Total Body Irradiation
• Date of first enrolment: January 14, 2009
• Target sample size: 62
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00856388
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: N/A

Countries of recruitment

United States

Contacts

• Name: George Chen
• Affiliation: Roswell Park Cancer Institute

Key inclusion & exclusion criteria

Inclusion Criteria:

- Diagnosis of a histology documented hematologic malignancy or marrow disorder

- Bone marrow failure disorders and other non-malignant hematologic or immunologic
disorders:

- Acquired bone marrow failure disorders include aplastic anemia, paroxysmal
nocturnal hemoglobinuria (PNH):

- Primary allogeneic hematopoietic stem cell transplantation (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 not available

- Patients with PNH must have a history of thrombosis related to PNH

- Hereditary bone marrow failure disorders include Fanconi anemia or related
chromosomal breakage syndrome dyskeratosis congenita, Diamond-Blackfan anemia,
Shwachman-Diamond syndrome, Kostmann syndrome, congenital amegakaryocytic
thrombocytopenia:

- Fanconi anemia or related chromosomal breakage syndrome: positive chromosome
breakage analysis using diepoxybutane (DEB) or mitomycin C if applicable

- Dyskeratosis: diagnosis is supported by using either telomerase reverse
transcriptase (TERC) gene mutation in autosomal dominant Dyskeratosis
Congenita or Xlinked 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 immunodeficiencies (including but not limited to Severe
Combined Immunodeficiency Syndrome, Wiskott-Aldrick syndrome, CD40 ligand
deficiency, T-cell deficiencies)

- Acute leukemias:

- Subjects must be ineligible for conventional myeloablative transplantation;

- Resistant or recurrent disease after at least one standard combination
chemotherapy regime or first remission patients at high risk of relapse 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 features (e.g. Flt3-ITD mutation, mixed-lineage leukemia [MLL],
wildtype NPM1);

- Acute lymphocytic leukemia (ALL)- high or standard risk ALL

- Chronic Myeloid Leukemia (CML):

- 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

- Myeloproliferative and myelodysplastic syndromes (MDS):

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

- Advanced polycythemia vera not responding to standard therapy

- MDS with an international prostate symptom score (IPSS) score of Int-2 or higher

- MDS with lower IPSS scores Int-1 or less with severe clinical features such as
severe neutropenia or thrombocytopenia or high risk chromosome abnormalities such
as monosomy 7

- Secondary massively parallel signature sequencing (MPSS) with any IPSS scores

- Chronic myelomoncytic leukemia

- Lymphoproliferative disease:

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

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

- Waldenstroms 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

- Hodgkin disease:

- Relapsed or refractory after front-line therapy

- Failed or were not eligible for autologous transplantation

- Failed prior autotransplant

- Age >= 3 and =< 75 years for blood and bone marrow transplants and age >= 3, < 60 for
cord blood transplants

- No serious uncontrolled psychiatric illness

- No concomitant active malignancy other than non-melanoma skin cancer

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

- Patients may have received prior autologous bone marrow transplant (BMT) or prior
myeloablative allogeneic BMT (at least 60 days have elapsed)

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

- Informed consent

- DONOR: Permissible HLA matching: Related donors- single antigen mismatch at HLA A, B
or DRB 1; unrelated donors- a single antigen mismatch at HLA A, B, or C, +/-
additional single allele level mismatch at A, B, C or DRB1; cord blood >= 4 out of 6
antigen match at HLA A, B, DRB1)

- 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


Age minimum: 3 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Adult Nasal Type Extranodal NK/T-cell Lymphoma

Angioimmunoblastic T-cell Lymphoma

Aplastic Anemia

Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue

Accelerated Phase Chronic Myelogenous Leukemia

Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)

Anaplastic Large Cell Lymphoma

Childhood Nasal Type Extranodal NK/T-cell Lymphoma

Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable

Stage III Marginal Zone Lymphoma

Nodal Marginal Zone B-cell Lymphoma

Noncontiguous Stage II Adult Burkitt Lymphoma

Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma

Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma

Noncontiguous Stage II Mantle Cell Lymphoma

Recurrent Adult Grade III Lymphomatoid Granulomatosis

Recurrent Adult Hodgkin Lymphoma

Recurrent Childhood Anaplastic Large Cell Lymphoma

Adult Acute Myeloid Leukemia With Del(5q)

Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome

Childhood Chronic Myelogenous Leukemia

Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative

Childhood Immunoblastic Large Cell Lymphoma

Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma

Noncontiguous Stage II Adult Lymphoblastic Lymphoma

Stage IV Adult Lymphoblastic Lymphoma

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities

Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)

Adult Acute Lymphoblastic Leukemia in Remission

Chronic Neutrophilic Leukemia

Recurrent Adult Acute Lymphoblastic Leukemia

Recurrent Adult Acute Myeloid Leukemia

Childhood Acute Myeloid Leukemia in Remission

Chronic Phase Chronic Myelogenous Leukemia

Recurrent Adult Diffuse Small Cleaved Cell Lymphoma

Recurrent Adult Immunoblastic Large Cell Lymphoma

Childhood Diffuse Large Cell Lymphoma

Chronic Myelomonocytic Leukemia

Recurrent Childhood Grade III Lymphomatoid Granulomatosis

Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma

Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)

Childhood Acute Lymphoblastic Leukemia in Remission

Recurrent Childhood Large Cell Lymphoma

Recurrent Childhood Lymphoblastic Lymphoma

Recurrent Marginal Zone Lymphoma

Stage III Adult Immunoblastic Large Cell Lymphoma

Recurrent Adult Lymphoblastic Lymphoma

Recurrent Childhood Acute Lymphoblastic Leukemia

de Novo Myelodysplastic Syndromes

Juvenile Myelomonocytic Leukemia

Waldenström Macroglobulinemia

Recurrent Small Lymphocytic Lymphoma

Recurrent/Refractory Childhood Hodgkin Lymphoma

Noncontiguous Stage II Grade 1 Follicular Lymphoma

Noncontiguous Stage II Small Lymphocytic Lymphoma

Refractory Chronic Lymphocytic Leukemia

Stage III Mantle Cell Lymphoma

Refractory Multiple Myeloma

Secondary Myelodysplastic Syndromes

Paroxysmal Nocturnal Hemoglobinuria

Recurrent Adult Diffuse Mixed Cell Lymphoma

Noncontiguous Stage II Marginal Zone Lymphoma

Primary Myelofibrosis

Stage IV Adult Immunoblastic Large Cell Lymphoma

Recurrent Childhood Acute Myeloid Leukemia

Recurrent Grade 1 Follicular Lymphoma

Stage III Small Lymphocytic Lymphoma

Stage IV Grade 2 Follicular Lymphoma

Recurrent Mantle Cell Lymphoma

Stage III Adult Diffuse Small Cleaved Cell Lymphoma

Childhood Myelodysplastic Syndromes

Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma

Noncontiguous Stage II Grade 2 Follicular Lymphoma

Noncontiguous Stage II Grade 3 Follicular Lymphoma

Previously Treated Myelodysplastic Syndromes

Recurrent Adult Diffuse Large Cell Lymphoma

Recurrent Adult T-cell Leukemia/Lymphoma

Recurrent Childhood Small Noncleaved Cell Lymphoma

Recurrent Adult Burkitt Lymphoma

Recurrent Grade 2 Follicular Lymphoma

Relapsing Chronic Myelogenous Leukemia

Secondary Acute Myeloid Leukemia

Stage III Grade 2 Follicular Lymphoma

Stage IV Adult Diffuse Small Cleaved Cell Lymphoma

Stage IV Adult Burkitt Lymphoma

Stage IV Mantle Cell Lymphoma

Stage III Adult Lymphoblastic Lymphoma

Stage IV Grade 1 Follicular Lymphoma

Stage IV Marginal Zone Lymphoma

Stage IV Small Lymphocytic Lymphoma

Adult Acute Myeloid Leukemia in Remission

Chronic Eosinophilic Leukemia

Fanconi Anemia

Recurrent Grade 3 Follicular Lymphoma

Recurrent Mycosis Fungoides/Sezary Syndrome

Splenic Marginal Zone Lymphoma

Stage III Grade 1 Follicular Lymphoma

Stage III Grade 3 Follicular Lymphoma

Stage IV Grade 3 Follicular Lymphoma

Intervention(s)

Biological: anti-thymocyte globulin

Drug: melphalan

Procedure: allogeneic hematopoietic stem cell transplantation

Radiation: total-body irradiation

Drug: fludarabine phosphate

Primary Outcome(s)

Day 100 TRM [Time Frame: First 100 days]

Secondary Outcome(s)

Acute GVHD Grade III-IV [Time Frame: Up to day 100]

Rate of Complete Donor Chimerism - Blood [Time Frame: Day 30]

1 yr Extenstive Chronic GVHD [Time Frame: Up to 4.5 years]

3 yr Overall Survival [Time Frame: Up to 4.5 years]

Median Time to ANC Engraftment [Time Frame: Days 30]

Rate of Complete Donor Chimerism - Blood [Time Frame: Day 100]

Median Time to Platelet Engraftment [Time Frame: Day 100]

Secondary ID(s)

I 118807

NCI-2009-01508

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Cancer Institute (NCI)

Results

• Results available: Yes
• Date Posted: 13/06/2016
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00856388