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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2011-00439 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| 1315.00 | Other Identifier | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | |
| P30CA015704 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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This phase II trial studies the side effects and how well giving busulfan and etoposide followed by peripheral blood stem cell transplant (PBSCT) and low-dose aldesleukin works in treating patients with acute myeloid leukemia (AML). Drugs used in chemotherapy, such as busulfan and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. A PBSCT may be able to replace blood-forming cells that were destroyed by chemotherapy. This may allow more chemotherapy to be given so that more cancer cells are killed. Aldesleukin may stimulate the white blood cells to kill cancer cells. Giving busulfan and etoposide together followed by PBSCT and aldesleukin may be an effective treatment for AML.
PRIMARY OBJECTIVES:
I. To evaluate the toxicity and overall survival of high dose Bu (busulfan)/VP-16 (etoposide) followed by post-transplant low-dose interleukin (IL)-2 (aldesleukin) in patients with AML.
SECONDARY OBJECTIVES:
I. To estimate the rate of relapse associated with this regimen.
OUTLINE:
PREPARATIVE REGIMEN: Patients receive busulfan intravenously (IV) over 2 hours or orally (PO) every 6 hours on days -7 to -4 and etoposide IV on day -3.
STEM CELL INFUSION: Patients undergo autologous or syngeneic PBSC rescue on day 0.
POST-TRANSPLANT ALDESLEUKIN THERAPY: Beginning 30-100 days after transplant, patients receive low-dose aldesleukin subcutaneously (SC) daily for 12 weeks.
After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (chemo, stem cell rescue, interleukin therapy) | Experimental | PREPARATIVE REGIMEN: Patients receive busulfan IV over 2 hours or PO every 6 hours on days -7 to -4 and etoposide IV on day -3. STEM CELL INFUSION: Patients undergo autologous or syngeneic PBSC rescue on day 0. POST-TRANSPLANT ALDESLEUKIN THERAPY: Beginning 30-100 days after transplant, patients receive low-dose aldesleukin SC daily for 12 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| busulfan | Drug | Given PO or IV |
|
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival of Patients on Busulfan and Etoposide Followed by Stem Cell Rescue and Aldesleukin | Estimated by the method of Kaplan and Meier. | From date of transplant to date of death from any cause, assessed up to 178 months |
| Toxicity Associated With High-dose Busulfan and Etoposide Followed by Stem Cell Rescue | Toxicity is defined as any grade 3 or grade 4 toxicity per the Bearman toxicity grading criteria following Busulfan and Etoposide high-dose chemotherapy, stem cell transplant, and the inability to recover sufficiently by day 100 to start IL-2 therapy. | Day -7 of transplant to 100 days post transplant |
| Toxicity Associated With Aldesleukin Treatment After Stem Cell Rescue | Toxicity during IL-2 therapy of any of the following per NCI Common Toxicity version 3: grade 2, 3, 4, or 5 CNS (except grade 0-3 malaise, fatigue, anxiety and depression) toxicity; grade 3, 4, or 5 non-CNS or non-hematologic toxicity; any grade 4 or 5 hematologic toxicity. | IL-2 administration to one month after completion of IL-2 treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Patients Who Relapsed Associated With the Regimen | From date of transplant to date of death from any cause, assessed up to 178 months |
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Inclusion Criteria:
The patient must have AML that falls into one of the following categories:
AML in 1st complete remission (CR) with intermediate or high risk of relapse following conventional therapy; at least, one of the following features is needed:
AML beyond first CR
Any patient with an identical twin donor who also meets the criteria above
Patients with AML in 1st CR should receive at least two cycles of consolidation chemotherapy prior to mobilization and transplant
Patients must have an adequate number of stem cells previously collected (i.e., > 2 x 10^8 total nucleated cell [TNC] of bone marrow [BM]/kg or 4 x 10^6 [CD]34+ PBSC/kg, unless approved otherwise by Dr. Holmberg); prior to stem cell collection patients must be documented to be in remission and to have received two cycles of consolidation therapy after induction therapy
Pre-Study tests have been performed
Patient must sign an institutional review board (IRB) approved informed consent, conforming with federal and institutional guidelines
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Leona Holmberg | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle | Washington | 98109 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42080799 | Derived | Lee Y, Kay MC, Palipana A, Askew S, Berger MB, Miller HN, Bennett GG, Yang Q. Identifying DASH Adherence Patterns and Their Association With Dietary Behaviors Among Adults With Hypertension. Res Nurs Health. 2026 May 4. doi: 10.1002/nur.70078. Online ahead of print. | |
| 34400362 | Derived | Miller HN, Berger MB, Askew S, Kay MC, Hopkins CM, Iragavarapu MS, de Leon M, Freed M, Barnes CN, Yang Q, Tyson CC, Svetkey LP, Bennett GG, Steinberg DM. The Nourish Protocol: A digital health randomized controlled trial to promote the DASH eating pattern among adults with hypertension. Contemp Clin Trials. 2021 Oct;109:106539. doi: 10.1016/j.cct.2021.106539. Epub 2021 Aug 13. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment (Chemo, Stem Cell Rescue, Interleukin Therapy) | PREPARATIVE REGIMEN: Patients receive busulfan IV over 2 hours or PO every 6 hours on days -7 to -4 and etoposide IV on day -3. STEM CELL INFUSION: Patients undergo autologous or syngeneic PBSC rescue on day 0. POST-TRANSPLANT ALDESLEUKIN THERAPY: Beginning 30-100 days after transplant, patients receive low-dose aldesleukin SC daily for 12 weeks. busulfan: Given PO or IV etoposide: Given IV aldesleukin: Given SC peripheral blood stem cell transplantation: Undergo autologous or syngeneic stem cell rescue |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| etoposide | Drug | Given IV |
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| aldesleukin | Biological | Given SC |
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| peripheral blood stem cell transplantation | Procedure | Undergo autologous or syngeneic stem cell rescue |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment (Chemo, Stem Cell Rescue, Interleukin Therapy) | PREPARATIVE REGIMEN: Patients receive busulfan IV over 2 hours or PO every 6 hours on days -7 to -4 and etoposide IV on day -3. STEM CELL INFUSION: Patients undergo autologous or syngeneic PBSC rescue on day 0. POST-TRANSPLANT ALDESLEUKIN THERAPY: Beginning 30-100 days after transplant, patients receive low-dose aldesleukin SC daily for 12 weeks. busulfan: Given PO or IV etoposide: Given IV aldesleukin: Given SC peripheral blood stem cell transplantation: Undergo autologous or syngeneic stem cell rescue |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Median | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Overall Survival of Patients on Busulfan and Etoposide Followed by Stem Cell Rescue and Aldesleukin | Estimated by the method of Kaplan and Meier. | Posted | Count of Participants | Participants | From date of transplant to date of death from any cause, assessed up to 178 months |
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| Primary | Toxicity Associated With High-dose Busulfan and Etoposide Followed by Stem Cell Rescue | Toxicity is defined as any grade 3 or grade 4 toxicity per the Bearman toxicity grading criteria following Busulfan and Etoposide high-dose chemotherapy, stem cell transplant, and the inability to recover sufficiently by day 100 to start IL-2 therapy. | Posted | Count of Participants | Participants | Day -7 of transplant to 100 days post transplant |
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| Primary | Toxicity Associated With Aldesleukin Treatment After Stem Cell Rescue | Toxicity during IL-2 therapy of any of the following per NCI Common Toxicity version 3: grade 2, 3, 4, or 5 CNS (except grade 0-3 malaise, fatigue, anxiety and depression) toxicity; grade 3, 4, or 5 non-CNS or non-hematologic toxicity; any grade 4 or 5 hematologic toxicity. | 29 patients underwent autologous transplant and 21 of these patients after transplant went on to get IL-2 treatment . Toxicity for IL-2 therapy thus was only analyzed in these later 21 patients. | Posted | Count of Participants | Participants | IL-2 administration to one month after completion of IL-2 treatment |
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| Secondary | Proportion of Patients Who Relapsed Associated With the Regimen | Posted | Count of Participants | Participants | From date of transplant to date of death from any cause, assessed up to 178 months |
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Day -7 pre transplant to approximately 212 days post transplant
Transplant (TX) toxicities grade ≥3 per Bearman toxicity grading measured day -7 to the start of IL-2 therapy.
Post-TX IL-2 therapy toxicities graded per NCI Common Toxicity version 3 measured from the start of IL-2 to one month after completion of IL-2: grade 2-5 CNS (except grade 0-3 malaise, fatigue, anxiety and depression) toxicity; grade 3- 5 non-CNS or non-hematologic toxicity; any grade 4 or 5 hematologic toxicity. 29 patients got TX and 21 patients got IL-2 after transplant.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment | PREPARATIVE REGIMEN: Patients receive busulfan IV over 2 hours or PO every 6 hours on days -7 to -4 and etoposide IV on day -3. STEM CELL INFUSION: Patients undergo autologous or syngeneic PBSC rescue on day 0. POST-TRANSPLANT ALDESLEUKIN THERAPY: Beginning 30-100 days after transplant, patients receive low-dose aldesleukin SC daily for 12 weeks. busulfan: Given PO or IV etoposide: Given IV aldesleukin: Given SC peripheral blood stem cell transplantation: Undergo autologous or syngeneic stem cell rescue | 0 | 29 | 5 | 29 | 29 | 29 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hospitalization for pulmonary embolus (likely from Hickman line) | Vascular disorders | Systematic Assessment | Transplant toxicity. Note: No SAEs in IL-2 portion of the study. |
| |
| Prolonged Hospitalization (34 days) for hyperbilirubinemia | Investigations | Systematic Assessment | Transplant toxicity. Note: No SAEs in IL-2 portion of the study. Possible autoimmune hemolysis or syngeneic GVHD and severe skin desquamation |
| |
| Hospitalization for infection | Infections and infestations | Systematic Assessment | Transplant toxicity. Note: No SAEs in IL-2 portion of the study. |
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| Stroke | Nervous system disorders | Systematic Assessment | Transplant toxicity. Note: No SAEs in IL-2 portion of the study. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Myelosuppression | Blood and lymphatic system disorders | Systematic Assessment | Transplant toxicity |
| |
| Hematologic | Blood and lymphatic system disorders | Systematic Assessment | NCI Common Toxicity Version 3 - Toxicity to IL-2 Therapy. Only 21 of 29 transplanted patients got IL-2 therapy. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Leona A. Holmberg | Fred Hutchinson Cancer Research Center | 206-667-6447 | lholmber@fredhutch.org |
| ID | Term |
|---|---|
| D000013 | Congenital Abnormalities |
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| D002066 | Busulfan |
| D005047 | Etoposide |
| C082598 | aldesleukin |
| D007376 | Interleukin-2 |
| D036102 | Peripheral Blood Stem Cell Transplantation |
| ID | Term |
|---|---|
| D002072 | Butylene Glycols |
| D006018 | Glycols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D008698 | Mesylates |
| D000476 | Alkanesulfonates |
| D017738 | Alkanesulfonic Acids |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
| D006838 | Hydrocarbons |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D013457 | Sulfur Compounds |
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D011083 | Polycyclic Compounds |
| D005960 | Glucosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D007378 | Interleukins |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D008222 | Lymphokines |
| D011506 | Proteins |
| D001685 | Biological Factors |
| D018380 | Hematopoietic Stem Cell Transplantation |
| D033581 | Stem Cell Transplantation |
| D017690 | Cell Transplantation |
| D064987 | Cell- and Tissue-Based Therapy |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D014180 | Transplantation |
| D013514 | Surgical Procedures, Operative |
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