Reduced Intensity Donor Peripheral Blood Stem Cell Transplant in Treating Patients With De Novo or Secondary Acute Myeloid Leukemia in Remission

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Clinical Trial

Official title:

Nonmyeloablative Allogeneic Peripheral Blood Stem Cell Transplantation From HLA Matched Related Donors for Treatment of Older Patients With De Novo or Secondary Acute Myeloid Leukemia in First Complete Remission

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00045435
• Other study ID #: 1654.00
• Secondary ID: NCI-2011-01307
• Status: Completed
• Phase: Phase 2
• Start date: April 2002
• Est. completion date: January 2009

Study information

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

Clinical Trial Summary

This phase II trial studies how well reduced intensity donor peripheral blood stem cell (PBSC) transplant works in treating patients with de novo or secondary acute myeloid leukemia (AML) in remission. Giving low doses of chemotherapy, such as fludarabine phosphate, and total-body irradiation (TBI) before a donor PBSC transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening

Description:

PRIMARY OBJECTIVES:

I. To determine if a one-year disease free survival of >= 35% can be achieved among patients >= 55 years old with de novo and secondary AML in first complete remission (CR1) who undergo nonmyeloablative hematopoietic stem cell transplant (HSCT) from human leukocyte antigen (HLA) identical related donors.

II. To determine if a day +200 nonrelapse related mortality of < 15% can be achieved among patients >= 55 years old with de novo and secondary AML in CR1 who undergo nonmyeloablative HSCT from HLA identical related donors.

OUTLINE:

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

TRANSPLANT: Patients undergo allogeneic PBSC transplant on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine (CSP) orally (PO) twice daily (BID) on days -3 to 56 with taper to day 77. Patients also receive mycophenolate mofetil (MMF) PO BID on days 0-27.

After completion of study treatment, patients are followed up on days 28, 56, and 84; months 6, 12, 18, and 24; and then yearly for 5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: January 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

Inclusion Criteria:

• Patients with de novo AML (French-American-British [FAB] MO-M2, M4-M7) or secondary AML who achieve CR1 after induction chemotherapy and one or two cycles of consolidation chemotherapy

• Transplant conditioning must occur within 6 months of diagnosis

• Patient enrollment must be approved by the Fred Hutchinson Cancer Research Center (FHCRC) principal investigator (PI) or the PI's designee

• DONOR: Related donor who is genotypically or phenotypically identical

• DONOR: Age >= 12 years

• 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:

• AML FAB M3

• AML involvement of the central nervous system (CNS) as defined by a positive cytospin of cerebral spinal fluid at the time of enrollment

• Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology

• Human immunodeficiency virus (HIV) seropositivity

• Fungal infections with radiographic progression after receipt of amphotericin B or active triazole for greater than one month

• Diffusion capacity of carbon monoxide (DLCO) corrected < 40%

• Total lung capacity (TLC) < 40%

• Forced expiratory volume in one second (FEV1) < 40% or requiring supplementary oxygen

• The FHCRC principal investigator of the study must approve enrollment of all patients with pulmonary nodules

• Cardiac ejection fraction < 40%

• Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension; patients will be excluded if they are 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 evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3mg/dL, or symptomatic biliary disease

• Karnofsky Performance Score < 70

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

• Females who are pregnant or breastfeeding

• No intensive chemotherapy can be given within three weeks (or the interval in which a cycle of standard chemotherapy would be administered in a non-transplant setting) prior to initiating the nonmyeloablative transplant conditioning

• Patients with active non-hematologic malignancies (except non-melanoma skin cancers)

• Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a > 20% risk of disease recurrence

• Patients with active bacterial or fungal infections unresponsive to medical therapy

• DONOR: Identical twin

• DONOR: Pregnancy

• DONOR: HIV seropositivity

• DONOR: Inability to achieve adequate venous access

• DONOR: Known allergy to G-CSF

• DONOR: Current serious systemic illness

Related Conditions & MeSH terms

• Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome
• Adult Acute Megakaryoblastic Leukemia (M7)
• Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
• Adult Acute Monoblastic Leukemia (M5a)
• Adult Acute Monocytic Leukemia (M5b)
• Adult Acute Myeloblastic Leukemia With Maturation (M2)
• Adult Acute Myeloblastic Leukemia Without Maturation (M1)
• 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(16;16)(p13;q22)
• Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
• Adult Acute Myelomonocytic Leukemia (M4)
• Adult Erythroleukemia (M6a)
• Adult Pure Erythroid Leukemia (M6b)
• Leukemia
• Leukemia, Erythroblastic, Acute
• Leukemia, Megakaryoblastic, Acute
• Leukemia, Monocytic, Acute
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Myelomonocytic, Acute
• Myelodysplastic Syndromes
• Neoplasm Metastasis
• Secondary Acute Myeloid Leukemia

Intervention

Procedure:
• nonmyeloablative allogeneic hematopoietic stem cell transplantation
Undergo nonmyeloablative allogeneic PBSC transplant

Drug:
• fludarabine phosphate
Given IV

Radiation:
• total-body irradiation
Undergo TBI

Drug:
• cyclosporine
Given PO
• mycophenolate mofetil
Given PO

Procedure:
• peripheral blood stem cell transplantation
Undergo nonmyeloablative allogeneic PBSC transplant

Locations

Country	Name	City	State
United States	OHSU Cancer Institute	Portland	Oregon
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free Survival-incidence of Survival Without Relapse	Sufficient evidence will be taken to be an observed rate of DFS at one year after transplant that corresponds to a one-sided 95% confidence interval with an upper limit lower than 35%.	By 1 year after transplant
Primary	Nonrelapse Mortality (NRM)-Incidence of Nonrelapse Death	Defined as death without morphologic evidence of disease. Sufficient evidence will be taken to be an observed rate of NRM within 200 days of transplant that corresponds to a one-sided 80% confidence interval with a lower limit greater than 15%.	200 days after transplant
Secondary	Overall Survival	Percent patients surviving.	By 1 year after transplant
Secondary	Incidence of Relapse	Percent patients with relapsed disease post-transplant.	By 1 year after transplant
Secondary	Incidence of Rejection	Percent patients who developed infections post-transplant.	By 1 year after transplant
Secondary	Incidence of Acute and Chronic GVHD	Percent patients with acute/chronic GVHD	aGVHD: 100 days after transplant; cGVHD: 1 Year after transplant.