Clinical trial NCT00630565: Stem Cell Transplant in Treating Patients With Acute Myeloid Leukemia
Official title: Autologous Peripheral Blood Stem Cell Transplant for Acute Non-Lymphocytic Leukemia (ANLL)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Leukemia
Keywords: adult acute myeloid leukemia in remission
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(8;21)(q22;q22)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with t(16;16)(p13;q22)
childhood acute myeloid leukemia in remission
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2008-03-07
Enrollment: 12
Sex: ALL
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Giving chemotherapy and colony-stimulating factors, such as G-CSF, may increase the number of stem cells in the blood. The stem cells are collected from the patient's blood and stored. Chemotherapy or radiation therapy is given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and radiation therapy.

PURPOSE: This clinical trial is studying how well an autologous stem cell transplant works in treating patients with acute myeloid leukemia.

Detailed description: OBJECTIVES:

* To assess whether sufficient peripheral blood stem cells (PBSC) can be collected from patients with acute myeloid leukemia (AML) using cyclophosphamide, etoposide, and granulocyte-colony stimulating factor (G-CSF) mobilization.
* To assess the rate of myeloid, platelet, and erythroid recovery following autologous PBSC transplant.
* To assess the disease-free survival rate of patients with AML receiving PBSC auto grafts.

OUTLINE:

* Chemotherapy and filgrastim (G-CSF) priming for PBSC collection: Patients receive cyclophosphamide IV on day 0; etoposide IV over 3 hours on days 0 and 1; and oral dexamethasone twice daily on days 0 and 1. Patients also receive G-CSF subcutaneously (SC) beginning on day 3 and continuing until apheresis is complete. After blood counts recover, apheresis is performed in 4-6 daily planned collections until the minimum CD34+ cell dose of \> 2.5 x 10\^6 cells/kg is achieved. If the minimum CD34+ cell dose is not achieved after 6 apheresis collections, patients undergo bone marrow examination including a bone marrow biopsy and aspiration, at the termination of the PBSC collection to confirm remission. If remission is confirmed, and if peripheral counts and marrow cellularity are sufficient, the patient remains off G-CSF for 7 days and receives sargramostim (GM-CSF) for 5 days to increase the marrow cellularity, after which a bone marrow harvest is performed.
* Bone marrow harvest without prior PBSC collection: Children will undergo primed bone marrow harvest comprising GM-CSF IV or SC for 5 days prior to harvest to increase cellularity and then marrow is harvested. Marrow and blood specimens are also obtained with the initial bone marrow evaluation and at the time of harvest if a cytogenetic abnormality was previously described. Other patients who are unable to undergo PBSC collection may proceed with a bone harvest at the discretion of the protocol chairperson.
* Cytoreductive regimen:

  * Patients over 2 years old: Patients undergo total body irradiation (TBI) twice daily on days -7 to -4 (total of 8 fractions), cyclophosphamide IV over 2 hours on days -3 and -2, followed by a 1-day rest period on day -1.
  * Patients under 2 years old and patients who cannot undergo TBI: Patients receive busulfan IV or orally every 6 hours on days -7 to -4, cyclophosphamide IV over 2 hours on days -3 to -2, followed by a 1-day rest period on day -1.
* Stem cell transplantation: All patients undergo autologous PBSC and/or bone marrow infusion on day 0. Patients also receive G-CSF IV or SC beginning on day 1 and continuing until blood counts recover.

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

Eligibility criteria: Inclusion Criteria:

Children under the age of two are eligible for this protocol, but will not receive total body irradiation. Instead, children under the age of two will receive Busulfan/Cyclophosphamide (Bu/Cy) conditioning as the preparative regimen in order to obviate deleterious effects of radiation at this age. Patients who cannot receive total body irradiation (TBI) (for example those with prior radiation therapy) will also receive the Bu/CY conditioning.

* Acute myeloid leukemia (AML)

  * All children and adults less than the age of 70 with AML who have achieved a first or second bone marrow remission are eligible for this protocol. Patients must undergo peripheral blood stem cell collection or marrow harvest while in remission and must not be expected to have better outcomes with allogeneic transplantation.
  * Patients with cytogenetic abnormalities suggesting an improved prognosis \[t(8:21), t(15;17) and inv(16)\] will be eligible for transplantation in first remission.
* Allogeneic transplant with an HLA-identical sibling will be recommended for patients \<55 years. If the patient refuses allogeneic transplant, they may still be eligible for this protocol.

Exclusion Criteria:

* Patients can also be deemed not eligible for transplant because of specific organ toxicity. Specifically, patients with pre-existing compromise to the heart, lungs, kidney, CNS or liver may be excluded:

  * Eastern Cooperative Oncology Group (ECOG) Performance status: 0 or 1
  * Heart - The patient must be free of symptoms of uncontrolled cardiac disease, and must not have compromised cardiac function detected by ECHO or by gated cardiac blood flow scan (MUGA) LVEF \>45%).
  * Kidney - The patient must have a corrected creatinine clearance \>50% of normal.
  * Liver - The total serum bilirubin \< 2.5 mg/dL; ALT \<2 x upper limit of normal.
  * Lung - Patients must have no significant obstructive airways disease or resting hypoxemia (PO2 \<80), and must have acceptable diffusion capacity (DLCO \> 50% of predicted).
  * Central Nervous System (CNS): Patients must be free of active or ongoing ischemic or degenerative CNS disease and no active or resistant CNS leukemia.

Primary outcomes:
measure: Percentage of Participants With Engraftment
timeFrame: 30 Days Post Transplant
Secondary outcomes:
measure: Percentage of Participants With Disease Response
timeFrame: 2 years Post Transplant
measure: Treatment Failure
timeFrame: 2 years Post Transplant
measure: Percent of Patients With Various Late Effects
timeFrame: 2 years Post Transplant
measure: Disease-free Survival
timeFrame: 2 years Post Transplant
measure: Percentage of Patients With Adequate Cells Collected
timeFrame: Pre-Transplant
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center, University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Daniel J. Weisdorf, MD
role: PRINCIPAL_INVESTIGATOR
References: