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LeukemiaPhase 2NCT02441803

Allogeneic Hematopoietic Stem Cell Transplantation (AlloSCT) Initial Salvage Therapy for Induction Failure Acute Myeloid Leukemia (AML)

A Phase 2 study testing Busulfan, Fludarabine and Clofarabine in people with Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Objectives: Primary Objectives: 1. To determine the safety and feasibility of allogeneic hematopoietic stem cell transplantation (AHSCT) as initial salvage treatment for patients with primary induction failure (PIF) acute myeloid leukemia (AML). 2. Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
Leukemia
What is being tested?
Busulfan, Fludarabine and Clofarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
1 siteUnited States
Study dates
14 Sep 2015to 22 Sep 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Patients age 18-60 years.
  • Patients with diagnosis of AML, judged primary refractory after up to 2 courses of AML induction therapy (> 5% blasts on day 21 (+/-7 days) bone marrow aspirate and/or biopsy from the beginning of induction chemotherapy, up to 42 days).
  • Eastern Cooperative Oncology Group (ECOG) Performance Status </= 2.
  • Adequate major organ function:, defined as: a) Serum creatinine </= 3 mg/dL; b) Total bilirubin </= 2.5 mg/dL; c) ALT (SGPT) </= 3 x ULN or </= 5 x ULN if related to disease; d) Cardiac ejection fraction >/= 40% (by either ECHO or MUGA).
  • Willingness to have an allogeneic transplant.
  • Patient or patient's legal representative able to provide written informed consent.
Show all 11Show fewer
  • Patients are required to meet the following criteria to proceed to AHSCT:
  • Donor criteria: Availability of a donor either an HLA matched sibling donor (MSD) or a haploidentical (5-9/10 HLA matched); alternatively a 8/8 HLA matched unrelated donor (MUD) by high resolution typing is immediately available;
  • Disease criteria: Day 21 (+/-7 days) bone marrow aspiration or biopsy from the beginning of salvage DCIA: a. In complete morphologic remission with <5% bone marrow blasts, or b. Aplastic (<10% bone marrow cellularity), and cytopenic with an absolute neutrophil count (ANC) less than 1,000/µL, or c. Low disease burden with < 30% BM blasts, with recovery of peripheral blood (PB) WBC (ANC>1,000/µL) and <5% circulating blasts.
  • Adequate organ function criteria: a. Serum creatinine clearance >/= 50 ml/min (calculated by Cockcroft-Gault formula); b. Total bilirubin </= 2 times upper limit of normal (x ULN) (3 x ULN if considered to be due to leukemic involvement or Gilbert's syndrome); c. Alanine aminotransferase (ALT) </= 3 x ULN (5.0 x ULN if considered to be due to leukemic involvement); d. LVEF >/= 40% on ECHO or MUGA; e. DLCO >/= 50% predicted after correction for hemoglobin (must be performed in patients with history of smoking or lung disease;); DLCO may be omitted in patients without history of pulmonary disease if approved by the Study Chair.
  • No active infection: Patients should be afebrile. If present, pulmonary infiltrates or other sites of infection must be improving on antibiotics. Patients should not require oxygen. Study Chair will be the arbiter of this criterion.

Who cannot join

  • HIV positive; active hepatitis B or C.
  • Uncontrolled active infections (viral, bacterial, and fungal); the Study Chair will be the final arbiter of this criterion.
  • Patients with active secondary malignancy unless approved by the Study Chair.
  • Liver cirrhosis.
  • Active CNS involvement within the previous 2 months.
  • Prior induction therapy with DAC + CIA.
Show all 10Show fewer
  • Positive pregnancy test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization.
  • Breast feeding women.
  • Men must agree not to father a child and agree to use a condom if his partner is of child bearing potential.
  • Inability to comply with medical therapy or follow-up.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Allogeneic Hematopoietic Stem Cell Transplantation as Initial Salvage Therapy for Patients With Primary Induction Failure Acute Myeloid Leukemia Refractory to High-Dose Cytarabine-Based Induction Chemotherapy

Objectives:

Primary Objectives:

Read more
  1. To determine the safety and feasibility of allogeneic hematopoietic stem cell transplantation (AHSCT) as initial salvage treatment for patients with primary induction failure (PIF) acute myeloid leukemia (AML).
  2. To determine efficacy of AHSCT following decitabine, clofarabine, idarubicin, and cytarabine (DCIA) salvage chemotherapy evaluated by overall response rate (RR), defined as complete response (CR) or CR without platelet recovery (CRp) or CR with insufficient hematological recovery (CRi).

Secondary Objectives:

  1. To determine the percentage of patients with PIF AML eligible for AHSCT after up to 2 courses of induction chemotherapy.
  2. To determine the early treatment-related mortality (TRM) (within first 4 weeks of first salvage chemotherapy regimen with DCIA and day 100 TRM after AHSCT.
  3. To determine the efficacy DCIA regimen as salvage chemotherapy for patients with PIF AML (% of patients who achieve </=5% bone marrow blasts prior to AHSCT.
  4. To determine the TRM at 1 year, relapse rate (RR), overall survival (OS) and event-free survival (EFS) for patients with PIF AML treated with DCIA followed by early AHSCT.
Read the detailed description

Salvage Chemotherapy Before Transplant:

Study Drug Administration:

On Days 1-5, you will receive decitabine 1 time each day by vein over about 1-3 hours.

On Days 6-10:

  • You will receive cytarabine 1 time a day by vein over about 1-3 hours.
  • On Days 6-8 only, you will receive idarubicin 1 time a day by vein over about 30 minutes.
  • On Days 6-9 only, you will receive clofarabine 1 time a day by vein over about 1-2 hours.

Study Visits:

After your last study drug dose:

  • Blood (about 2 teaspoons) will be drawn to check your kidney and liver function.
  • You will have an echocardiogram (ECHO) or multigated acquisition (MUGA) scan to check your heart function.
  • You will have a lung function test.

On Day 21 (+/- 7 days), you will have a bone marrow biopsy/aspirate to check the status of the disease. To collect a bone marrow biopsy/aspirate, an area of the hip is numbed with anesthetic, and a small amount of bone and bone marrow is withdrawn through a large needle.

If the results of your bone marrow biopsy/aspirate, blood tests, and heart and lung function tests show that you are eligible to receive an allogeneic stem cell transplant, you will be asked to sign a separate informed consent for the transplant.

If the results of your bone marrow aspirate/biopsy, blood tests, and heart and lung function tests show that you are not eligible to receive an allogeneic stem cell transplant you will not receive it. The study staff will call you and ask how you are feeling and about any other drugs you may be taking every 3 months for 2 years after your last study drug dose. These calls should last about 5 minutes each.

If you are found to NOT be eligible to receive an allogeneic stem cell transplant, your doctor will discuss other treatment options with you.

Stem Cell Transplant:

Study Drug Administration, Pharmacokinetic (PK) Testing, and Stem Cell Transplant:

For a stem cell transplant, the days before you receive your stem cells are called minus days. The day you receive the stem cells is called Day 0. The days after you receive the stem cells are called plus days.

You will receive a dose of busulfan by vein over about 45 minutes to 1 hour as an outpatient or as an inpatient on Day -8. With the first busulfan infusion, blood (about 1 teaspoon each time) will be drawn for pharmacokinetic (PK) testing about 11 times over 11 hours before and after you receive your first dose of busulfan. PK testing measures the amount of study drug in the body at different time points. The study staff will tell you the blood testing schedule. Test doses are used to study how your body breaks down busulfan and decide the dose of busulfan that you will receive on Days -6 through -3.

A heparin lock line will be placed in your vein before the PK testing to lower the number of needle sticks needed for these draws. If for any reason it is not possible for the PK tests to be performed, you will receive the standard dose of busulfan.

On Day -7, you will rest.

On Days -6 through -3, you will receive fludarabine by vein over 1 hour, clofarabine by vein over 1 hour, and then busulfan by vein over 3 hours.

On Days -3 and -2, if you will receive stem cells from a matched unrelated donor, you will receive ATG by vein over 4 hours each day.

On Day -2, if you will receive stem cells from a haploidentical donor, you will receive total body irradiation (TBI) one time. TBI involves the delivery of high doses of radiation designed to destroy cancer cells and/or lower the immune system in order to lower the risk of the body rejecting the new stem cells.

On Day -2, you will receive tacrolimus by vein over 24 hours every day until you are able to take it by mouth. Tacrolimus is designed to weaken the immune system and lower the risk of graft-versus-host-disease (GVHD - a reaction of the donor's immune cells against your body). After you are able to take tacrolimus by mouth, you will take it every day for about 6 months, or until the doctor thinks it is safe to stop.

On Day -1, you will rest. If you will receive stem cells from a matched sibling donor, you will rest on Days -2 and -1.

On Day 0, you will receive the donor's stem cells by vein. The infusion will last anywhere from about 30 minutes to several hours.

If you will receive stem cells from a haploidentical donor:

After the stem cell infusion, you will receive tacrolimus to help lower the risk of GVHD. Tacrolimus will be given by vein non-stop for about 2 weeks. After the 2 weeks of taking tacrolimus by vein, you will take tacrolimus by mouth as a pill for at least 4 months after the transplant.

On Days +3 and +4, you will receive cyclophosphamide by vein over 3 hours. Cyclophosphamide is given to lower the immune system in order to lower the risk of GVHD.

If you receive stem cells from a matched sibling or matched unrelated donor:

On Days +1, +3, +6, and +11, you will receive methotrexate by vein over 30 minutes. Methotrexate is given to help prevent GVHD.

Study Testing:

Before you are sent home from the hospital and/or clinic, you will receive additional written instructions. These instructions will include how often you will come to the hospital/clinic, which standard drugs you will take at home, and what side effects you may have and what to do for them.

After finishing the chemotherapy and transplant, your follow-up care will be routine standard of care follow-up that all patients receiving allogeneic stem cell transplantation receive. At each visit, you will have a physical exam. You will be asked about any side effects you may have had. Blood (about 1 tablespoon) will be drawn for routine tests. If the doctor thinks it is needed, you will have a bone marrow aspiration to check the status of the disease. To collect a bone marrow aspirate, an area of the hip or other site is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle.

Length of Treatment:

After 2 years, your participation in this study will be over. You may be taken off study early if the disease gets worse, if your transplant does not "take" (graft failure), if you are unable to follow study directions, if your doctor thinks it is in your best interest, if the study is stopped, or if you choose to leave the study early.

If for any reason you want to leave the study early, you must talk to the study doctor. It may be life-threatening to leave the study after you have started to receive the study drugs but before you receive the stem cell transplant because your blood cell counts will be dangerously low.

Conditions
Leukemia
Being tested
Busulfan, Fludarabine, Clofarabine, Total Body Irradiation (TBI), Thymoglobulin
Keywords
Leukemia, Acute myeloid leukemia, AML, Refractory, Allogeneic hematopoietic stem cell transplantation, AHSCT, Busulfan, Busulfex, Myleran, Fludarabine, Fludarabine Phosphate, Fludara, Clofarabine, Clofarex, Clolar, Total body irradiation, TBI, XRT, Thymoglobulin, ATG (Rabbit)
Medical subject headings
Leukemia, Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BusulfanDrug

    Also called Busulfex, Myleran

    Test dose Busulfan 32 mg/m2 given by vein on Day -8. Busulfan AUC 5,000 by vein on Days -6 to -3.

  • FludarabineDrug

    Also called Fludarabine Phosphate, Fludara

    Fludarabine 10 mg/m2 by vein on Days -6 to -3.

  • ClofarabineDrug

    Also called Clofarex, Clolar

    Salvage Chemotherapy Before Transplant: Clofarabine 15 mg/m2 by vein on Days 6 - 9.

    Stem Cell Transplant: Clofarabine 40 mg/m2 by vein on Days -6 to -3.

  • Total Body Irradiation (TBI)Radiation

    Also called TBI, XRT

    Total body irradiation (TBI) delivered at 2Gy on Day -2.

  • ThymoglobulinDrug

    Also called ATG (Rabbit), Rabbit Antithymocyte Globulin, Rabbit Antilymphocyte Globulin, Rabbit ATG

    Thymoglobulin 2.0 mg/Kg by vein on Days -3 and -2.

  • Stem Cell InfusionBiological

    Fresh or cryopreserved bone marrow or peripheral blood (PB) progenitor cells infused on Day 0. Goal is to infuse 4 X 106 CD34+ cells/kg if PB or >3.0 X 108 marrow mononuclear cells/kg if bone marrow.

  • CyclophosphamideDrug

    Also called Cytoxan, Neosar

    Cyclophosphamide 50 mg/kg by vein on Days +3 and +4.

  • TacrolimusDrug

    Also called Prograf

    Tacrolimus 0.015 mg/kg/day by vein or mouth on Day +5.

  • Mycophenolate mofetilDrug

    Also called MMF, CellCept

    Mycophenolate mofetil 15 mg/kg/dose by vein or by mouth three times a day from Day +5 to Day+100.

  • DecitabineDrug

    Also called Dacogen

    20 mg/m2 by vein on Days 1 - 5.

  • CytarabineDrug

    Also called Ara-C, Cytosar, DepoCyt, Cytosine Arabinosine Hydrochloride

    1 g/m2 by vein on Days 6 - 10.

  • IdarubicinDrug

    Also called Idamycin

    10 mg/m2 by vein on Days 6 - 8.

Study groups in NCT02441803
Study groupRoleWhat they receive
Matched Sibling Donor GroupExperimentalSalvage Chemotherapy Before Transplant: Decitabine 20 mg/m2 by vein on Days 1 - 5. Cytarabine 1 g/m2 by vein on Days 6 - 10. Idarubicin 10 mg/m2 by vein on Days 6 - 8. Clofarabine 15 mg/m2 by vein on Days 6 - 9. Stem Cell Transplant: Test dose Busulfan 32 mg/m2 by vein on Day -8. Busulfan AUC 5,000 by vein on Days -6 to -3. Fludarabine 10 mg/m2 by vein on Days -6 to -3. Clofarabine 40 mg/m2 by vein on Days -6 to -3. Stem cell infusion performed on Day 0.
Receives: Drug: Busulfan; Drug: Fludarabine; Drug: Clofarabine; Biological: Stem Cell Infusion; Drug: Decitabine; Drug: Cytarabine; Drug: Idarubicin
Haploidentical Donor GroupExperimentalSalvage Chemotherapy Before Transplant: Decitabine 20 mg/m2 by vein on Days 1 - 5. Cytarabine 1 g/m2 by vein on Days 6 - 10. Idarubicin 10 mg/m2 by vein on Days 6 - 8. Clofarabine 15 mg/m2 by vein on Days 6 - 9. Stem Cell Transplant: Test dose Busulfan 32 mg/m2 given by vein on Day -8. Busulfan AUC 5,000 by vein on Days -6 to -3. Fludarabine 10 mg/m2 by vein on Days -6 to -3. Clofarabine 40 mg/m2 by vein on Days -6 to -3. Total body irradiation (TBI) delivered at 2Gy on Day -2. Stem cell infusion performed on Day 0. Cyclophosphamide 50 mg/kg by vein on Days +3 and +4. Tacrolimus 0.015 mg/kg/day by vein or mouth on Day +5. Mycophenolate mofetil 15 mg/kg/dose by vein or by mouth three times a day from Day +5 to Day+100.
Receives: Drug: Busulfan; Drug: Fludarabine; Drug: Clofarabine; Radiation: Total Body Irradiation (TBI); Biological: Stem Cell Infusion; Drug: Cyclophosphamide; Drug: Tacrolimus; Drug: Mycophenolate mofetil; Drug: Decitabine; Drug: Cytarabine; Drug: Idarubicin
Matched Unrelated Donor GroupExperimentalSalvage Chemotherapy Before Transplant: Decitabine 20 mg/m2 by vein on Days 1 - 5. Cytarabine 1 g/m2 by vein on Days 6 - 10. Idarubicin 10 mg/m2 by vein on Days 6 - 8. Clofarabine 15 mg/m2 by vein on Days 6 - 9. Stem Cell Transplant: Test dose Busulfan 32 mg/m2 given by vein on Day -8. Busulfan AUC 5,000 by vein on Days -6 to -3. Fludarabine 10 mg/m2 by vein on Days -6 to -3. Clofarabine 40 mg/m2 by vein on Days -6 to -3. Thymoglobulin 2.0 mg/Kg by vein on Days -3 and -2. Stem cell infusion performed on Day 0.
Receives: Drug: Busulfan; Drug: Fludarabine; Drug: Clofarabine; Drug: Thymoglobulin; Biological: Stem Cell Infusion; Drug: Decitabine; Drug: Cytarabine; Drug: Idarubicin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response (OR) Post Transplant

    Number of participants classified as achieving overall response of complete remission(CR: < 5% blast in a bone marrow/and platelet >100/and ANC >1) or CR without platelet recovery (CRp: < 5% blast in a bone marrow/and platelet <100/and ANC >1) or CR with insufficient hematological recovery (CRi: < 5% blast in a bone marrow/and platelet >100/and ANC <1) post transplant.

    Measured: 4 months after initial treatment/3 months after transplant

  2. Treatment-Related Mortality (TRM)

    Number of participants died from treatment-related death within 4 months post initial treatment/3 months post transplant.

    Measured: 4 months post initial treatment/3 months post transplant

Secondary outcomes (1)

  1. Overall Survival (OS)

    Number of participants alive and disease free in 1 year post transplant.

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 May 2015 (estimated)
  2. Study start14 Sep 2015
  3. Primary completion22 Sep 2020
  4. Study completion22 Sep 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02441803
Sponsor's protocol ID
2014-0358
Other IDs
NCI-2015-00849
Status last verified
Feb 2024
First submitted
5 May 2015
Last updated
22 Feb 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Busulfan, Fludarabine and Clofarabine in people with Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response (OR) Post Transplant (time frame: 4 months after initial treatment/3 months after transplant). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02441803.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2024.

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