Fludarabine Phosphate and Total-Body Radiation Followed by Donor Peripheral Blood Stem Cell Transplant and Immunosuppression in Treating Patients With Hematologic Malignancies

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT00014235
• Date of registration: 10/04/2001
• Prospective Registration: No
• Primary sponsor: Fred Hutchinson Cancer Research Center
• Public title: Fludarabine Phosphate and Total-Body Radiation Followed by Donor Peripheral Blood Stem Cell Transplant and Immunosuppression in Treating Patients With Hematologic Malignancies
• Scientific title: Nonmyeloablative PBSC Allografting From HLA Matched Related Donors Using Fludarabine and/or Low Dose TBI With Disease-Risk Based Immunosuppression
• Date of first enrolment: December 2000
• Target sample size: 160
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00014235
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: N/A

Countries of recruitment

Germany, Italy, United States

Contacts

• Name: David Maloney
• Affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Key inclusion & exclusion criteria

Inclusion Criteria:

- Patients with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) or
multiple myeloma who are not eligible for a curative autologous transplantation or who
have received a prior autologous transplantation; patients with NHL or CLL must have
failed prior therapy with an alkylating agent and/or fludarabine, or be at high risk
of relapse; patients with multiple myeloma must have stage II or III disease and
received prior chemotherapy

- Patients < 50 years of age with NHL, Hodgkin's disease (HD), CLL or multiple myeloma
at high risk of regimen related toxicity through prior autologous transplant or
through pre-existing medical conditions

- Patients < 75 years of age with other malignant diseases treatable by allogeneic bone
marrow transplant (BMT) whom through pre-existing chronic disease affecting kidneys,
liver, lungs, and heart are considered to be at high risk for regimen related toxicity
using standard high dose regimens; the following diseases are the likely candidates

- Myelodysplastic syndromes

- Myeloproliferative syndromes

- Acute Leukemia with < 10% blasts

- Amyloidosis

- Hodgkin's disease

- The Fred Hutchinson Cancer Research Center (FHCRC) Patient Care Conference (PCC) may
approve patients with other malignancies or patients declining standard allografts for
transplant following presentation and approval; centers outside the FHCRC that have a
PCC or equivalent should obtain their Institutional approval; if there is not a
comparable group at the Institution, please contact the FHCRC Principal Investigator
for FHCRC approval through PCC

- DONOR: Human leukocyte antigen (HLA) genotypically or phenotypically identical related
donor

- DONOR: Donor must consent to filgrastim (G-CSF) administration and leukapheresis

- DONOR: Donor must have adequate veins for leukapheresis or agree to placement of
central venous catheter (femoral, subclavian)

Exclusion Criteria:

- Eligible for a high-priority curative autologous transplant

- Patients with rapidly progressive aggressive NHL unless in minimal disease state

- Any current central nervous system (CNS) involvement with disease

- Fertile men or women unwilling to use contraceptive techniques during and for 12
months following treatment

- Females who are pregnant

- Patients who are human immunodeficiency virus (HIV) positive

- Cardiac ejection fraction < 40%; ejection fraction is required if the patient has a
history of anthracyclines or history of cardiac disease

- Receiving supplementary continuous oxygen

- Diffusing capacity of the lung for carbon monoxide (DLCO) < 30%

- Total lung capacity (TLC) < 30%

- Forced expiratory volume in one second (FEV1) < 30%

- Total bilirubin > 2x the upper limit of normal

- Serum glutamate pyruvate transaminase (SGPT) and serum glutamic oxaloacetic
transaminase (SGOT) 4x the upper limit of normal

- Karnofsky score < 50

- Patients with poorly controlled hypertension who are unable to have blood pressure
kept below 150/90 on standard medication

- Patients with renal failure are eligible, however patients with renal compromise
(serum creatinine greater than 2.0) will likely have further compromise in renal
function and may require hemodialysis (which may be permanent) due to the need to
maintain adequate serum cyclosporine levels

- The addition of cytotoxic agents for "cytoreduction" with the exception of hydroxyurea
and imatinib mesylate will not be allowed within two weeks of the initiation of
conditioning

- DONOR: Identical twin

- DONOR: Age less than 12 years

- DONOR: Pregnancy

- DONOR: Infection with HIV

- DONOR: Inability to achieve adequate venous access

- DONOR: Known allergy to G-CSF

- DONOR: Current serious systemic illness



Age minimum: N/A
Age maximum: 74 Years
Gender: All

Health Condition(s) or Problem(s) studied

Acute Myeloid Leukemia/Transient Myeloproliferative Disorder

Acute Undifferentiated Leukemia

Adult Acute Myeloid Leukemia With Del(5q)

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

Childhood Acute Lymphoblastic Leukemia in Remission

Childhood Burkitt Lymphoma

Adult Acute Lymphoblastic Leukemia in Remission

Adult Nasal Type Extranodal NK/T-cell Lymphoma

Childhood Nasal Type Extranodal NK/T-cell Lymphoma

Cutaneous B-cell Non-Hodgkin Lymphoma

Chronic Myelomonocytic Leukemia

Primary Systemic Amyloidosis

Hepatosplenic T-cell Lymphoma

Recurrent Adult Acute Lymphoblastic Leukemia

Recurrent Adult Diffuse Small Cleaved Cell Lymphoma

Recurrent Childhood Lymphoblastic Lymphoma

Recurrent Grade 2 Follicular Lymphoma

Recurrent Mantle Cell Lymphoma

Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma

Recurrent Small Lymphocytic Lymphoma

Splenic Marginal Zone Lymphoma

Stage III Multiple Myeloma

Adult Acute Myeloid Leukemia in Remission

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

T-cell Large Granular Lymphocyte Leukemia

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities

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

Childhood Myelodysplastic Syndromes

de Novo Myelodysplastic Syndromes

Childhood Acute Myeloid Leukemia in Remission

Juvenile Myelomonocytic Leukemia

Childhood Immunoblastic Large Cell Lymphoma

Mast Cell Leukemia

Nodal Marginal Zone B-cell Lymphoma

Noncutaneous Extranodal Lymphoma

Recurrent Childhood Large Cell Lymphoma

Refractory Hairy Cell Leukemia

Recurrent Adult Diffuse Mixed Cell Lymphoma

Recurrent Childhood Acute Myeloid Leukemia

Post-transplant Lymphoproliferative Disorder

Previously Treated Myelodysplastic Syndromes

Recurrent Grade 3 Follicular Lymphoma

Recurrent Mycosis Fungoides/Sezary Syndrome

Recurrent Adult Diffuse Large Cell Lymphoma

Recurrent Adult Immunoblastic Large Cell Lymphoma

Untreated Adult Acute Myeloid Leukemia

Untreated Childhood Acute Lymphoblastic Leukemia

Anaplastic Large Cell Lymphoma

Peripheral T-cell Lymphoma

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

Childhood Diffuse Large Cell Lymphoma

Angioimmunoblastic T-cell Lymphoma

Blastic Plasmacytoid Dendritic Cell Neoplasm

Recurrent Adult Lymphoblastic Lymphoma

Recurrent Adult T-cell Leukemia/Lymphoma

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

Recurrent Adult Acute Myeloid Leukemia

Recurrent Adult Grade III Lymphomatoid Granulomatosis

Recurrent Adult Hodgkin Lymphoma

Recurrent Childhood Acute Lymphoblastic Leukemia

Recurrent Childhood Grade III Lymphomatoid Granulomatosis

Recurrent Childhood Small Noncleaved Cell Lymphoma

Recurrent Grade 1 Follicular Lymphoma

Recurrent Adult Burkitt Lymphoma

Recurrent Childhood Anaplastic Large Cell Lymphoma

Recurrent/Refractory Childhood Hodgkin Lymphoma

Refractory Chronic Lymphocytic Leukemia

Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

Recurrent Marginal Zone Lymphoma

Intraocular Lymphoma

Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable

Refractory Multiple Myeloma

Small Intestine Lymphoma

Stage II Multiple Myeloma

Untreated Adult Acute Lymphoblastic Leukemia

Testicular Lymphoma

Waldenström Macroglobulinemia

Intervention(s)

Drug: mycophenolate mofetil

Other: laboratory biomarker analysis

Procedure: allogeneic hematopoietic stem cell transplantation

Radiation: total-body irradiation

Procedure: peripheral blood stem cell transplantation

Drug: fludarabine phosphate

Drug: cyclosporine

Primary Outcome(s)

Probability of severe (grade III/IV) GVHD in each arm [Time Frame: Up to 5 years]

Probability of severe (grade III/IV) GVHD in each arm [Time Frame: Up to day 84]

Secondary Outcome(s)

Incidence of graft rejection [Time Frame: Day 84]

Incidence of graft rejection [Time Frame: Day 56]

Severity of infectious complications [Time Frame: Up to 5 years]

Incidence of graft rejection [Time Frame: Day 28]

Incidence of graft rejection [Time Frame: Day 180]

Incidence of graft rejection [Time Frame: Day 365]

Incidence of infectious complications [Time Frame: Up to 5 years]

Incidence of non-relapse mortality [Time Frame: Up to 5 years]

Secondary ID(s)

1596.00

NCI-2012-00671

P30CA015704

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Heart, Lung, and Blood Institute (NHLBI)

National Cancer Institute (NCI)