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

NCT00045435 | Completed Phase 2 Results DMC

• 2 other identifiers: 1654.00NCI-2011-01307
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief 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

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 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); Secondary Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Overall Survival

  By 1 year after transplant

• Incidence of Relapse

  By 1 year after transplant

• Incidence of Rejection

  By 1 year after transplant

• Incidence of Acute and Chronic GVHD

  aGVHD: 100 days after transplant; cGVHD: 1 Year after transplant.

Study Arms (1)

Treatment (nonmyeloablative donor PBSC transplant)

EXPERIMENTAL

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.

Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation; Drug: fludarabine phosphate; Radiation: total-body irradiation; Drug: cyclosporine; Drug: mycophenolate mofetil; Procedure: peripheral blood stem cell transplantation

Interventions

nonmyeloablative allogeneic hematopoietic stem cell transplantation PROCEDURE

Undergo nonmyeloablative allogeneic PBSC transplant

Treatment (nonmyeloablative donor PBSC transplant)

fludarabine phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara

Treatment (nonmyeloablative donor PBSC transplant)

total-body irradiation RADIATION

Undergo TBI

Also known as: TBI

Treatment (nonmyeloablative donor PBSC transplant)

cyclosporine DRUG

Given PO

Also known as: ciclosporin, cyclosporin, cyclosporin A, CYSP, Sandimmune

Treatment (nonmyeloablative donor PBSC transplant)

mycophenolate mofetil DRUG

Given PO

Also known as: Cellcept, MMF

Treatment (nonmyeloablative donor PBSC transplant)

peripheral blood stem cell transplantation PROCEDURE

Undergo nonmyeloablative allogeneic PBSC transplant

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

Treatment (nonmyeloablative donor PBSC transplant)

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

OHSU Cancer Institute

Portland, Oregon, 97210, United States

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• 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.

  PMID: 32499241 DERIVED

MeSH Terms

Conditions

Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Congenital Abnormalities; Leukemia, Myelomonocytic, Acute; Leukemia, Erythroblastic, Acute

Interventions

fludarabine phosphate; Whole-Body Irradiation; Cyclosporine; Mycophenolic Acid; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Myeloproliferative Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Investigative Techniques; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. Brenda M. Sandmaier
• Organization: Fred Hutchinson Cancer Research Center

bsandmai@fhcrc.org

206-667-4961

Study Officials

• Brenda Sandmaier

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 6, 2002
• First Posted: January 27, 2003
• Study Start: April 1, 2002
• Primary Completion: January 1, 2009
• Study Completion: January 1, 2009
• Last Updated: January 29, 2020
• Results First Posted: March 16, 2017

Record last verified: 2020-01

Locations

US (2)