Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00014235
Other study ID # 1596.00
Secondary ID NCI-2012-0067115
Status Completed
Phase N/A
First received
Last updated
Start date December 2000

Study information

Verified date January 2020
Source Fred Hutchinson Cancer Research Center
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This clinical trial studies fludarabine phosphate and total-body radiation followed by donor peripheral blood stem cell transplant and immunosuppression in treating patients with hematologic malignancies. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy 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 total-body irradiation together with fludarabine phosphate, cyclosporine, and mycophenolate mofetil before transplant may stop this from happening.


Description:

PRIMARY OBJECTIVES:

I. To estimate the rate of grade III/IV graft-versus-host disease (GVHD) in patients treated with low-dose total body irradiation (TBI), fludarabine (fludarabine phosphate), PBSC infusion and immunosuppression with mycophenolate mofetil and a disease risk-based cyclosporine taper.

II. To estimate the risk of graft rejection, GVHD, disease response, non-relapse mortality and the incidence and severity of infectious complications using this treatment strategy.

OUTLINE: Patients are assigned to 1 of 2 treatment groups.

ARM I (indolent disease):

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2 and undergo TBI on day 0.

TRANSPLANTATION: Patients undergo donor peripheral blood stem cell transplantation (PBSCT) on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) or IV every 8-12 hours on days -3 to 56 with a taper to day 180 and mycophenolate mofetil PO BID or IV every 8-12 hours on days 0 to 27.

ARM II (aggressive disease):

CONDITIONING REGIMEN: Patients receive fludarabine phosphate and undergo TBI as in Arm I.

TRANSPLANTATION: Patients undergo donor PBSCT on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID or IV every 8-12 hours on days -3 to 56 with a taper to day 70 and mycophenolate mofetil as in Arm I.

After completion of study treatment, patients are followed up for 5 years.


Recruitment information / eligibility

Status Completed
Enrollment 160
Est. completion date
Est. primary completion date February 2005
Accepts healthy volunteers No
Gender All
Age group N/A to 74 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms

  • Acute Myeloid Leukemia/Transient Myeloproliferative Disorder
  • Acute Undifferentiated 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 Nasal Type Extranodal NK/T-cell Lymphoma
  • Amyloidosis
  • Anaplastic Large Cell Lymphoma
  • Angioimmunoblastic T-cell Lymphoma
  • Blastic Plasmacytoid Dendritic Cell Neoplasm
  • Burkitt Lymphoma
  • Childhood Acute Lymphoblastic Leukemia in Remission
  • Childhood Acute Myeloid Leukemia in Remission
  • Childhood Burkitt Lymphoma
  • Childhood Diffuse Large Cell Lymphoma
  • Childhood Immunoblastic Large Cell Lymphoma
  • Childhood Myelodysplastic Syndromes
  • Childhood Nasal Type Extranodal NK/T-cell Lymphoma
  • Chronic Myelomonocytic Leukemia
  • Cutaneous B-cell Non-Hodgkin Lymphoma
  • de Novo Myelodysplastic Syndromes
  • Disease
  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Hepatosplenic T-cell Lymphoma
  • Hodgkin Disease
  • Immunoglobulin Light-chain Amyloidosis
  • Intraocular Lymphoma
  • Juvenile Myelomonocytic Leukemia
  • Leukemia
  • Leukemia, Hairy Cell
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Leukemia, Mast-Cell
  • Leukemia, Myeloid
  • Leukemia, Myeloid, Acute
  • Leukemia, Myelomonocytic, Acute
  • Leukemia, Myelomonocytic, Chronic
  • Leukemia, Myelomonocytic, Juvenile
  • Leukemia, T-Cell
  • Leukemia-Lymphoma, Adult T-Cell
  • Lymphoma
  • Lymphoma, B-Cell
  • Lymphoma, B-Cell, Marginal Zone
  • Lymphoma, Extranodal NK-T-Cell
  • Lymphoma, Follicular
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Large-Cell, Anaplastic
  • Lymphoma, Large-Cell, Immunoblastic
  • Lymphoma, Mantle-Cell
  • Lymphoma, Non-Hodgkin
  • Lymphoma, T-Cell
  • Lymphoma, T-Cell, Cutaneous
  • Lymphoma, T-Cell, Peripheral
  • Lymphomatoid Granulomatosis
  • Lymphoproliferative Disorders
  • Mast Cell Leukemia
  • Multiple Myeloma
  • Mycoses
  • Mycosis Fungoides
  • Myelodysplastic Syndromes
  • Myelodysplastic-Myeloproliferative Diseases
  • Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
  • Myeloproliferative Disorders
  • Neoplasms
  • Neoplasms, Plasma Cell
  • Nodal Marginal Zone B-cell Lymphoma
  • Noncutaneous Extranodal Lymphoma
  • Peripheral T-cell Lymphoma
  • Plasmablastic Lymphoma
  • Post-transplant Lymphoproliferative Disorder
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Preleukemia
  • Previously Treated Myelodysplastic Syndromes
  • Primary Systemic Amyloidosis
  • 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
  • Sezary Syndrome
  • Small Intestine Lymphoma
  • Splenic Marginal Zone Lymphoma
  • Stage II Multiple Myeloma
  • Stage III Multiple Myeloma
  • Syndrome
  • T-cell Large Granular Lymphocyte Leukemia
  • Testicular Lymphoma
  • Untreated Adult Acute Lymphoblastic Leukemia
  • Untreated Adult Acute Myeloid Leukemia
  • Untreated Childhood Acute Lymphoblastic Leukemia
  • Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies
  • Waldenstrom Macroglobulinemia
  • Waldenström Macroglobulinemia

Intervention

Drug:
fludarabine phosphate
Given IV
Radiation:
total-body irradiation
Undergo TBI
Procedure:
peripheral blood stem cell transplantation
Undergo PBSCT
allogeneic hematopoietic stem cell transplantation
Undergo PBSCT
Drug:
cyclosporine
Given PO or IV
mycophenolate mofetil
Given IV or PO
Other:
laboratory biomarker analysis
Correlative studies

Locations

Country Name City State
Germany Universitaet Leipzig Leipzig
Italy University of Torino Torino
United States Baylor University Medical Center Dallas Texas
United States City of Hope Medical Center Duarte California
United States Froedtert Hospital Milwaukee Wisconsin
United States OHSU Knight Cancer Institute Portland Oregon
United States Huntsman Cancer Institute/University of Utah Salt Lake City Utah
United States LDS Hospital Salt Lake City Utah
United States Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle Washington
United States Stanford University Hospitals and Clinics Stanford California
United States University of Arizona Health Sciences Center Tucson Arizona

Sponsors (3)

Lead Sponsor Collaborator
Fred Hutchinson Cancer Research Center National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

United States,  Germany,  Italy, 

Outcome

Type Measure Description Time frame Safety issue
Primary Probability of severe (grade III/IV) GVHD in each arm 95% confidence interval will be calculated. Up to day 84
Primary Probability of severe (grade III/IV) GVHD in each arm 95% confidence intervals will be calculated. Up to 5 years
Secondary Incidence of graft rejection Chimerism analysis by fluorescent in situ hybridization (FISH) or variable number tandem repeat (VNTR). Examined and reported in a descriptive manner. Confidence intervals will be presented. Day 28
Secondary Incidence of graft rejection Chimerism analysis by FISH or VNTR. Examined and reported in a descriptive manner. Confidence intervals will be presented. Day 56
Secondary Incidence of graft rejection Chimerism analysis by FISH or VNTR. Examined and reported in a descriptive manner. Confidence intervals will be presented. Day 84
Secondary Incidence of graft rejection Chimerism analysis by FISH or VNTR. Examined and reported in a descriptive manner. Confidence intervals will be presented. Day 180
Secondary Incidence of graft rejection Chimerism analysis by FISH or VNTR. Examined and reported in a descriptive manner. Confidence intervals will be presented. Day 365
Secondary Incidence of non-relapse mortality Examined and reported in a descriptive manner. Confidence intervals will be presented. Up to 5 years
Secondary Incidence of infectious complications Examined and reported in a descriptive manner. Confidence intervals will be presented. Up to 5 years
Secondary Severity of infectious complications Examined and reported in a descriptive manner. Confidence intervals will be presented. Up to 5 years
See also
  Status Clinical Trial Phase
Enrolling by invitation NCT04093570 - A Study for Participants Who Participated in Prior Clinical Studies of ASTX727 (Standard Dose), With a Food Effect Substudy at Select Study Centers Phase 2
Active, not recruiting NCT03289910 - Topotecan Hydrochloride and Carboplatin With or Without Veliparib in Treating Advanced Myeloproliferative Disorders and Acute Myeloid Leukemia or Chronic Myelomonocytic Leukemia Phase 2
Recruiting NCT06159491 - Pacritinib in CMML Phase 1/Phase 2
Completed NCT01427881 - Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies Phase 2
Recruiting NCT01133886 - Use of Decitabine in Myelodysplastic Syndrome (MDS) Following Azacitidine (AZA) Failure Phase 2
Completed NCT01169012 - PK Study of Oral and IV Clofarabine in High Risk Myelodysplasia+Acute Leukemias Phase 1
Completed NCT01233921 - Palifermin in Preventing Chronic Graft-Versus-Host Disease in Patients Who Have Undergone Donor Stem Cell Transplant for Hematologic Cancer N/A
Completed NCT01093586 - Donor Umbilical Cord Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies Phase 2
Terminated NCT00509249 - Aflibercept in Treating Patients With Myelodysplastic Syndromes Phase 2
Terminated NCT00387426 - Sunitinib in Treating Patients With Idiopathic Myelofibrosis Phase 2
Completed NCT00096122 - Idarubicin, Cytarabine, and Tipifarnib in Treating Patients With Newly Diagnosed Myelodysplastic Syndromes or Acute Myeloid Leukemia Phase 1/Phase 2
Completed NCT00171912 - Imatinib Mesylate in Patients With Various Types of Malignancies Involving Activated Tyrosine Kinase Enzymes Phase 2
Completed NCT00078858 - Mycophenolate Mofetil and Cyclosporine in Reducing Graft-Versus-Host Disease in Patients With Hematologic Malignancies or Metastatic Kidney Cancer Undergoing Donor Stem Cell Transplant Phase 1/Phase 2
Completed NCT00052520 - Biological Therapy in Treating Patients With Advanced Myelodysplastic Syndrome, Acute or Chronic Myeloid Leukemia, or Acute Lymphoblastic Leukemia Who Are Undergoing Stem Cell Transplantation Phase 1/Phase 2
Recruiting NCT03683433 - Enasidenib and Azacitidine in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia and IDH2 Gene Mutation Phase 2
Recruiting NCT04980404 - Inqovi Maintenance Therapy in Myeloid Neoplasms Phase 1
Active, not recruiting NCT03588078 - Study of the Safety and Efficacy of APR-246 in Combination With Azacitidine Phase 1/Phase 2
Withdrawn NCT06085638 - Phase I/II Study of SY-1425 (Tamibarotene) in Combination With Azacitidine and Venetoclax for Patients With Chronic Myelomonocytic Leukemia Phase 1/Phase 2
Recruiting NCT03999723 - Combining Active and Passive DNA Hypomethylation Phase 2
Terminated NCT00852709 - Phase I Dose-Escalation Trial of Clofarabine Followed by Escalating Doses of Fractionated Cyclophosphamide in Children With Relapsed or Refractory Acute Leukemias Phase 1