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Adult Acute Megakaryoblastic Leukemia (M7)Phase 1NCT01801046

Donor Stem Cell Transplant in Treating Patients With High Risk Acute Myeloid Leukemia

A Phase 1 study testing mitoxantrone hydrochloride, cytarabine and peripheral blood stem cell transplantation in people with Adult Acute Megakaryoblastic Leukemia (M7) and Adult Acute Monoblastic Leukemia (M5a), run by University of Southern California at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase I trial studies the side effects of donor stem cell transplant in treating patients with high risk acute myeloid leukemia. Giving low doses of chemotherapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. Read more about this study

Who is it for?
Any age
What is being tested?
mitoxantrone hydrochloride, cytarabine and peripheral blood stem cell transplantation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteUnited States
Study dates
6 Mar 2013to 20 Aug 2017
Phase
Phase 1
Are there results?
None posted in the registry

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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Patients must have a histologically and cytological confirmed acute myeloid leukemia, high risk AML defined as:
  • Age > 60, or
  • Presence of complex cytogenetic abnormalities (with > 3 cytogenetic abnormalities), del (7q, -5, -7), t(9,22), 11q(23) or high risk mutations by FISH eg MLL, FLT-3 +
  • Secondary AML, or
  • A white blood cell count of > 50 x10^9/L
  • Patients must be medically ineligible for allogeneic stem cell transplant (alloSCTx) or not have a known fully HLA matched sibling for planned sibling transplant.
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  • Patients must have measurable or evaluable disease
  • Diagnosis of AML according to World Health Organization (WHO) diagnostic criteria (at least 20% blasts in the peripheral blood or bone marrow), with French-American-British Cooperative group (FAB) classification other than M3 (acute promyelocytic leukemia), documented by bone marrow aspiration and biopsy performed within 14 days prior to administration of 1st dose of remission induction chemotherapy; if a bone marrow aspirate and biopsy were obtained within 28 days prior to the first dose of remission induction therapy then these tests may be submitted for review at University of Southern California (USC) and a repeat screening bone marrow does not need to be conducted;
  • Cohort A: newly diagnosed AML, no prior cytotoxic chemotherapy
  • Cohort B: newly diagnosed AML, failed to achieve Complete remission (CR) with single standard Induction chemo.
  • Patient has at least one medically fit family member expected to be HLA mismatched at 1-9/10; more commonly and preferred: 4-6/10 loci (parent, sibling, niece/nephew, etc but adult children preferred)
  • Absolute neutrophil count (ANC) > 1500, unless due to direct bone marrow involvement of disease
  • Platelets > 75,000, unless due to direct bone marrow involvement of disease
  • Hemoglobin > 8.0 gm/dL, transfusion allowed
  • Serum creatinine < 2.0 x the upper limits of institutional normal (ULN)
  • Total bilirubin < 1.5 x the upper limits of institutional normal
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT )< 2.5 x the upper limits of institutional normal (=< 5 x ULN for patients with liver involvement of leukemia)
  • Cardiac left ventricular ejection fraction (LVEF) > 45%
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Estimated survival of at least 3 months
  • Patients must be able to understand and agree to sign an Institutional Review Board (IRB)-approved informed consent form
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry, for the duration of study, and for two months after study participation
  • DONOR: Donor screening; all donors will meet the standard blood donor criteria established by the participating local blood center, American Association of Blood Banks (AABB)
  • DONOR: Donors will be selected from among the subject's relatives, adult children preferred
  • DONOR: Infectious disease testing will be done per Hemacare policy and AAAB guidelines
  • DONOR: Donor and intended recipient red cell type and compatibility will be determined
  • DONOR: Donors will be pre-selected on the basis of HLA haploidentity
  • DONOR: If patient is cytomegalovirus (CMV)-negative, donors who are CMV-negative will be preferred; CMV serology of the donor will be tested prior to the allogeneic cell donation; donations from CMV-positive donors to CMV-negative recipients will be given if no CMV negative donor is available, and CMV surveillance and pre-emptive treatment given

Who cannot join

  • Cohort A: Patients who have received prior cytotoxic chemotherapy, such as anthracyclines and cytarabine not permitted; but prior treatment with demethylating agents (azacytidine or decitabine, lenalidomide, etc) ALLOWED.
  • Cohort B: Patients who have received prior fludarabine, clorarabine or drugs known to target T cells not permitted; but prior standard induction with anthracylines and cytarabine ALLOWED including after demethylating agents.
  • Have uncontrolled systemic infections, coagulation disorders, or other major medical illnesses of the cardiovascular or respiratory systems
  • Pregnant and/or lactating
  • Patients who have had non-biopsy surgery in the last 10 days
  • Active central nervous system (CNS) disease; patients with previously treated leptomeningeal disease without evidence of remaining leukemia cells by spinal fluid will be eligible
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  • Known active autoimmune disorder
  • Known to be human immunodeficiency virus (HIV)-positive or have active hepatitis B or C
  • Patients concurrently taking the following drugs are excluded: mycophenolate, cyclosporine, prednisone > 20mg/day, or immunosuppressive agents
  • DONOR: Personal or family history of severe sickle cell disease or variant (unless donor has tested negative); testing for the presence of hemoglobin S is not required
  • DONOR: Positive infectious disease test as dictated by blood collection center's standard operating procedure (SOP)
  • DONOR: Current uncontrolled hypertension
  • DONOR: Diabetes mellitus
  • DONOR: Active peptic ulcer disease
  • DONOR: Pregnant or breast-feeding
  • DONOR: Currently taking lithium therapy
  • DONOR: History of autoimmune disease
  • DONOR: History of coronary disease

Trial locations and contacts

1 site in 1 country.

United States1 site

  • USC Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

Other trials in United States

About this study

Official title: HLA-mismatched Allogeneic Cellular Therapy (HMMACT) After Chemotherapy in High Risk Acute Myeloid Leukemia

This phase I trial studies the side effects of donor stem cell transplant in treating patients with high risk acute myeloid leukemia. Giving low doses of chemotherapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells when they do not exactly match the patient's blood. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect)

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the feasibility of cytarabine based chemotherapy and human leukocyte antigen (HLA)-mismatched allogeneic cellular therapy (HMMACT) in patients with high risk acute myeloid leukemia (AML), with feasibility measured by induction mortality (IM) and complete response rate.

SECONDARY OBJECTIVES:

  1. To obtain preliminary estimates of clinical outcome following cytarabine based chemotherapy and HMMACT in patients with high risk AML, as measured by event free survival (EFS) and overall survival (OS).

II. To further evaluate the safety outcomes of induction and consolidation of cytarabine and HMMACT in terms of serious infections (grade 4), time to recovery of absolute neutrophil counts and platelets and incidence of graft versus host disease (GvHD).

III. To further evaluate the feasibility of this approach in terms of identifying a suitable donor in this elderly population.

IV. To compare in preliminary manner the clinical outcomes of cytarabine and HMMACT in patients with high risk AML as measured by complete response rate (CRR), event free survival (EFS) and overall survival (OS) by donor/recipient HLA-C1 vs C2 pairs.

  1. To characterize in a preliminary manner, the numbers of suppressor regulatory T cells (Tregs), T helper 17 cells (Th17), and cytotoxic T cells during pre and post HMMACT treatment, and with clinical outcomes in leukemia.

OUTLINE:

INDUCTION CHEMOTHERAPY: Patients receive mitoxantrone hydrochloride intravenously (IV) on days 1-3 and cytarabine IV on days 1-7.

HMMACT: Patients receive filgrastim (G-CSF) mobilized peripheral blood stem cells (G-PBSC) on day 9. After completion of study treatment, patients are followed up monthly for 3 years.

Being tested
mitoxantrone hydrochloride, cytarabine, peripheral blood stem cell transplantation, laboratory biomarker analysis
Medical subject headings
Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, Acute, Congenital Abnormalities, Leukemia, Myelomonocytic, Acute, Leukemia, Erythroblastic, Acute

What participants receive

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

  • mitoxantrone hydrochlorideDrug

    Also called CL 232315, DHAD, DHAQ, Novantrone

    Given IV

  • cytarabineDrug

    Also called ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U

    Given IV

  • peripheral blood stem cell transplantationProcedure or surgery

    Also called PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

    Undergo HMMACT with G-PBSC

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT01801046
Study groupRoleWhat they receive
Treatment (chemotherapy, G-PBSC)ExperimentalINDUCTION CHEMOTHERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-3 and cytarabine IV on days 1-7. HMMACT: Patients receive G-PBSC on day 9.
Receives: Drug: mitoxantrone hydrochloride; Drug: cytarabine; Procedure: peripheral blood stem cell transplantation; Other: laboratory biomarker analysis

What is being measured

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

  1. Induction mortality

    Measured: Up to 8 weeks

  2. Complete remission rate (complete remission [CR] or incomplete remission [CRi])

    Exact 95% confidence intervals will be constructed.

    Measured: Up to 3 years

Secondary outcomes (6)

  1. Occurrence of serious infections (grade 4) assessed using National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) v4.0

    Will be summarized in terms of type, severity, attribution, time of onset, duration, reversibility, and outcome.

    Measured: Up to 3 years

  2. Time to recovery of absolute neutrophil counts (ANC)

    Will be summarized using cumulative incidence curves.

    Measured: From stem cell infusion to the first of 3 consecutive days in which the ANC is more than 0.5 x 10^9/L, assessed up to 3 years

  3. Time to recovery of platelets

    Will be summarized using cumulative incidence curves.

    Measured: From stem cell infusion until the first of 3 consecutive days in which the platelet count is more than 30 x 10^9/L, assessed up to 3 years

  4. Incidence of GvHD

    Will be reported in terms of grade, site, and time of onset (for acute GvHD) and whether limited or extensive, and time of onset (for chronic GvHD).

    Measured: Up to 3 years

  5. Estimate of clinical outcome as measured by event free survival (EFS)

    Kaplan-Meier plots will be used to summarize the EFS observed in this series. The proportion of patients alive and in continuous complete remission will be estimated at 6, 12, 18, and 24 months. 95% intervals will be constructed.

    Measured: From the start of induction until documentation of failure to achieve a CR or CRi during induction, initiation of a salvage therapy, disease recurrence/progression (after induction), or death due to any cause, assessed up to 2 years

  6. Estimate of clinical outcome as measured by overall survival (OS)

    Kaplan-Meier plots will be used to summarize the OS observed in this series. The proportion of patients alive will be estimated at 6, 12, 18, and 24 months. 95% intervals will be constructed.

    Measured: From the start of induction until death due to any cause, assessed up to 2 years

Timeline

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

  1. First posted28 Feb 2013 (estimated)
  2. Study start6 Mar 2013
  3. Primary completion27 Jul 2017
  4. Study completion20 Aug 2017

Why it stopped: Insufficient Accrual

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01801046
Sponsor's protocol ID
9L-11-8
Other IDs
NCI-2013-00447
Status last verified
Mar 2018
First submitted
26 Feb 2013
Last updated
30 Mar 2018
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing mitoxantrone hydrochloride, cytarabine and peripheral blood stem cell transplantation in people with Adult Acute Megakaryoblastic Leukemia (M7) and Adult Acute Monoblastic Leukemia (M5a), run by University of Southern California 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 28 inclusion and 18 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: stopped early, as of the sponsor's last update on 30 Mar 2018. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study was stopped early (reason given: Insufficient Accrual). Results are not available in the source record.

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?

Induction mortality (time frame: Up to 8 weeks). 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 NCT01801046.

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 30 Mar 2018.

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