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

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

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

Study Overview

• Status: Completed
• Conditions: 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 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); Secondary Acute Myeloid Leukemia; Adult Acute Myeloid Leukemia in Remission
• Intervention / Treatment: Drug: fludarabine phosphate; Radiation: total-body irradiation; Drug: mycophenolate mofetil; Drug: cyclosporine; Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97210
      • OHSU Cancer Institute
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (nonmyeloablative donor PBSC transplant); CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. TRANSPLANT: Patients undergo allogeneic PBSC transplant on day 0. IMMUNOSUPPRESSION: Patients receive CSP PO BID on days -3 to 56 with taper to day 77. Patients also receive MMF PO BID on days 0-27.

Drug: fludarabine phosphate; Given IV; Other Names: 2-F-ara-AMP; Beneflur; Fludara; Radiation: total-body irradiation; Undergo TBI; Other Names: TBI; Drug: mycophenolate mofetil; Given PO; Other Names: Cellcept; MMF; Drug: cyclosporine; Given PO; Other Names: ciclosporin; cyclosporin; cyclosporin A; CYSP; Sandimmune; Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation; Undergo nonmyeloablative allogeneic PBSC transplant; Procedure: peripheral blood stem cell transplantation; Undergo nonmyeloablative allogeneic PBSC transplant; Other Names: PBPC transplantation; PBSC transplantation; peripheral blood progenitor cell transplantation; transplantation, peripheral blood stem cell

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Percent patients surviving.	By 1 year after transplant
Incidence of Relapse	Percent patients with relapsed disease post-transplant.	By 1 year after transplant
Incidence of Rejection	Percent patients who developed infections post-transplant.	By 1 year after transplant
Incidence of Acute and Chronic GVHD	Percent patients with acute/chronic GVHD	aGVHD: 100 days after transplant; cGVHD: 1 Year after transplant.

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Cooper JP, Storer BE, Granot N, Gyurkocza B, Sorror ML, Chauncey TR, Shizuru J, Franke GN, Maris MB, Boyer M, Bruno B, Sahebi F, Langston AA, Hari P, Agura ED, Lykke Petersen S, Maziarz RT, Bethge W, Asch J, Gutman JA, Olesen G, Yeager AM, Hubel K, Hogan WJ, Maloney DG, Mielcarek M, Martin PJ, Flowers MED, Georges GE, Woolfrey AE, Deeg JH, Scott BL, McDonald GB, Storb R, Sandmaier BM. Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades. Haematologica. 2021 Jun 1;106(6):1599-1607. doi: 10.3324/haematol.2020.248187.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2002
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): January 1, 2009

Study Registration Dates

• First Submitted: September 6, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): January 29, 2020
• Last Update Submitted That Met QC Criteria: January 15, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Neoplastic Processes; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasm Metastasis; Leukemia, Myelomonocytic, Acute; Leukemia, Monocytic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Erythroblastic, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Fludarabine; Fludarabine phosphate; Mycophenolic Acid; Cyclosporine; Cyclosporins
• Other Study ID Numbers: 1654.00; NCI-2011-01307 (Registry Identifier: CTRP (Clinical Trial Reporting Program))