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Acute Biphenotypic LeukemiaPhase 2NCT01028716

Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

A Phase 2 study testing Cyclophosphamide, Filgrastim and Fludarabine Phosphate in people with Acute Biphenotypic Leukemia and Acute Erythroid Leukemia in Remission, run by Fred Hutchinson Cancer Center 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 II trial studies how well donor peripheral blood stem cell (PBSC) transplant works in treating patients with hematologic malignancies. Cyclophosphamide when added to tacrolimus and mycophenolate mofetil is safe and effective in preventing severe graft-versus-host disease (GVHD) in most patients with… Read more about this study

Who is it for?
Any age
What is being tested?
Cyclophosphamide, Filgrastim and Fludarabine Phosphate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
1 siteUnited States
Study dates
19 May 2010to 7 Oct 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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Molecular based human leukocyte antigen (HLA) typing will be performed for the HLA-A, -B, -Cw, -DRB1 and -DQB1 loci to the resolution adequate to establish haplo-identity; a minimum match of 5/10 is required; an unrelated donor search is not required for a patient to be eligible for this protocol if the clinical situation dictates an urgent transplant; clinical urgency is defined as 6-8 weeks from referral or low-likelihood of finding a matched, unrelated donor
  • Acute leukemias (includes T lymphoblastic lymphoma); remission is defined as < 5% blasts with no morphological characteristics of acute leukemia (e.g., Auer rods) in a bone marrow with > 20% cellularity, peripheral blood counts showing ANC > 1000/ul, including patients in complete remission with incomplete platelet recovery (CRp); if the marrow has < 20% cellularity due to treatment related cytotoxicity, but still has < 5% blasts, an exception may be made to include this patient up to principal investigator (PI) discretion
  • Acute lymphoblastic leukemia in high risk first complete remission (CR1) as defined by at least one of the following:
  • Adverse cytogenetics including but not limited to t(9;22), t(1;19), t(4;11), mixed lineage leukemia (MLL) rearrangements
  • White blood cell counts > 30,000/mcL
  • Patients over 30 years of age
Show all 42Show fewer
  • Time to complete remission > 4 weeks
  • Presence of extramedullary disease
  • Minimal residual disease
  • Other risk factors determined by the patient's attending physician to be high risk features requiring transplantation
  • Acute myelogenous leukemia in high risk CR1 as defined by at least one of the following:
  • Greater than 1 cycle of induction therapy required to achieve remission
  • Preceding myelodysplastic syndrome (MDS)
  • Presence of fms-like tyrosine kinase receptor-3 (Flt3) abnormalities
  • French-American-British (FAB) M6 or M7 leukemia, or
  • Adverse cytogenetics for overall survival such as:
  • Those associated with MDS
  • Complex karyotype (>= 3 abnormalities); or
  • Any of the following: inv(3) or t(3;3), t(6;9), t(6;11), + 8 [alone or with other abnormalities except for t(8;21), t(9;11), inv(16) or t(16;16)], t(11;19)(q23;p13.1)]
  • Other risk factors determined by the patient's attending physician to be high risk features requiring transplantation
  • Acute leukemias in second (2nd) or subsequent remission
  • Biphenotypic/undifferentiated leukemias in first (1st) or subsequent complete remission (CR)
  • High-risk MDS status-post cytotoxic chemotherapy
  • Burkitt's lymphoma: second or subsequent CR
  • Chemotherapy-sensitive (at least stable disease) large cell, mantle cell or Hodgkin's lymphomas that have failed at least 1 prior regimen of multi-agent chemotherapy and are ineligible for an autologous transplant
  • Marginal zone B-cell lymphoma or follicular lymphoma that has progressed after at least two prior therapies (excluding single agent Rituxan)
  • Multiple myeloma (MM) stage II or III patients who have progressed after an initial response to chemotherapy or autologous hematopoietic stem cell transplantation (HSCT) or MM patients with refractory disease who may benefit from tandem autologous-nonmyeloablative allogeneic transplant
  • Left ventricular ejection fraction at rest must be >= 35%
  • Bilirubin =< 2.5 mg/dL
  • Alanine aminotransferase (ALT) < 5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) < 5 x ULN
  • Alkaline phosphatase < 5 x ULN
  • Serum creatinine within normal range for age, or if serum creatinine outside normal range for age, then renal function (creatinine clearance or glomerular filtration rate [GFR]) > 40 mL/min/1.73m^2
  • Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), diffusion capacity of carbon monoxide (DLCO) (diffusion capacity) >= 40% predicted (corrected for hemoglobin); if unable to perform pulmonary function tests, then oxygen (O2) saturation > 92% on room air
  • Karnofsky/Lansky score >= 60%
  • Patients who have received a prior allogeneic HSCT and who have either rejected their grafts or who have become tolerant of their grafts with no active GVHD requiring immunosuppressive therapy
  • Patients will undergo standard pre-transplant work-up as dictated by standard practice guidelines the results of which may be used for screening for this study
  • DONOR: Donors must be HLA-haploidentical first-degree relatives of the patient; eligible donors include biological parents, siblings, or children, or half-siblings
  • DONOR: Age >= 12 years
  • DONOR: Weight >= 40 kg
  • DONOR: Ability of donors < 18 years of age to undergo apheresis without use of a vascular access device; vein check must be performed and verified by an apheresis nurse prior to arrival at the Seattle Cancer Care Alliance (SCCA)
  • DONOR: Donors must meet the selection criteria as defined by the Foundation for the Accreditation of Cell Therapy (FACT) and will be screened per the American Association of Blood Banks (AABB) guidelines

Who cannot join

  • HLA-matched or single allele-mismatched donor able to donate
  • Pregnancy or breast-feeding
  • Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings)
  • Patients with primary idiopathic myelofibrosis
  • DONOR: Positive anti-donor HLA antibody

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: Nonmyeloablative Hematopoietic Cell Transplantation (HCT) for Patients With Hematologic Malignancies Using Related, HLA-Haploidentical Donors: A Phase II Trial of Peripheral Blood Stem Cells (PBSC) as the Donor Source

This phase II trial studies how well donor peripheral blood stem cell (PBSC) transplant works in treating patients with hematologic malignancies. Cyclophosphamide when added to tacrolimus and mycophenolate mofetil is safe and effective in preventing severe graft-versus-host disease (GVHD) in most patients with hematologic malignancies undergoing transplantation of bone marrow from half-matched (haploidentical) donors. This approach has extended the transplant option to patients who do not have matched related or unrelated donors, especially for patients from ethnic minority groups. The graft contains cells of the donor's immune system which potentially can recognize and destroy the patient's cancer cells (graft-versus-tumor effect). Rejection of the donor's cells by the patient's own immune system is prevented by giving low doses of chemotherapy (fludarabine phosphate and cyclophosphamide) and total-body irradiation before transplant. Patients can experience low blood cell counts after transplant. Using stem cells and immune cells collected from the donor's circulating blood may result in quicker recovery of blood counts and may be more effective in treating the patient's disease than using bone marrow.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To demonstrate that use of PBSC in place of marrow as the source of lymphocytes and stem cells for nonmyeloablative transplants from related, haploidentical donors will not result in unacceptable rates of high-grade acute or chronic GVHD, non-relapse mortality or relapse compared to historical data on nonmyeloablative transplants from unrelated donors.

SECONDARY OBJECTIVES:

  1. Estimates of the rates of neutrophil and platelet recovery, number of red blood cell (RBC) and platelet transfusions, incidences of graft failure, transplant-related toxicities, disease-free survival and overall survival.

OUTLINE:

Patients receive fludarabine intravenously (IV) over 30-60 minutes daily on days -6 through -2 and cyclophosphamide IV over 1-2 hours on days -6, -5, and 3-4. Patients undergo total-body irradiation on day -1. Patients undergo donor peripheral blood stem cell transplant on day 0. Patients then receive tacrolimus IV once daily or orally (PO) twice daily (BID) on days 5-180 (may be continued if active GVHD is present), mycophenolate mofetil IV or PO thrice daily (TID) on days 5-35 (may be continued if GVHD present), and filgrastim IV beginning on day 5 until the absolute neutrophil count (ANC) is >= 1,000/mm^3 for three consecutive days.

Treatment continues in the absence of disease progression or unacceptable toxicity.

Being tested
Cyclophosphamide, Filgrastim, Fludarabine Phosphate, Mycophenolate Mofetil, Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Medical subject headings
Leukemia, Biphenotypic, Acute, Burkitt Lymphoma, Myelodysplastic Syndromes, Lymphoma, Large-Cell, Anaplastic, Lymphoma, Follicular, Hodgkin Disease, Lymphoma, Mantle-Cell, Lymphoma, B-Cell, Marginal Zone

What participants receive

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

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • FilgrastimBiological

    Also called Filgrastim XM02, Filgrastim-sndz, G-CSF, Neupogen

    Given SQ

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara

    Given IV

  • Mycophenolate MofetilDrug

    Also called Cellcept, MMF

    Given PO

  • Nonmyeloablative Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called Non-myeloablative allogeneic transplant, Nonmyeloablative Stem Cell Transplantation, NST

    Undergo PBSC

  • Peripheral Blood Stem Cell TransplantationProcedure or surgery

    Also called PBPC transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant

    Undergo PBSC

  • TacrolimusDrug

    Also called FK 506, Fujimycin, Hecoria, Prograf

    Given IV or PO

  • Total-Body IrradiationRadiation

    Also called TOTAL BODY IRRADIATION, Whole-Body Irradiation

    Undergo total-body irradiation (TBI)

Study groups in NCT01028716
Study groupRoleWhat they receive
Treatment (nonmyeloablative HCT, TBI)ExperimentalPatients receive fludarabine IV over 30-60 minutes daily on days -6 through -2 and cyclophosphamide IV over 1-2 hours on days -6, -5, and 3-4. Patients undergo total-body irradiation on day -1. Patients undergo donor peripheral blood stem cell transplant on day 0. Patients then receive tacrolimus IV once daily or PO BID on days 5-180 (may be continued if active GvHD is present), mycophenolate mofetil IV or PO TID on days 5-35 (may be continued if GvHD present), and filgrastim IV beginning on day 5 until the ANC is >= 1,000/mm^3 for three consecutive days.
Receives: Drug: Cyclophosphamide; Biological: Filgrastim; Drug: Fludarabine Phosphate; Drug: Mycophenolate Mofetil; Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Peripheral Blood Stem Cell Transplantation; Drug: Tacrolimus; Radiation: Total-Body Irradiation

What is being measured

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

  1. Non-relapse Mortality at 1 Year

    Cumulative incidence of death without evidence of disease progression at 1 year

    Measured: Up to 1 year

  2. Percentage of Participants With Chronic Graft Versus Host Disease

    Scored according to the National Cancer Institute criteria. Mild-to-severe chronic GVHD at 2 years.

    Measured: Up to 2 years post-transplant

  3. Incidence of Grades III/IV Acute Graft Versus Host Disease

    Grading determined by organ system stages. Grade III/IV acute graft versus host disease is defined as skin: stage IV, liver: stages II-IV, and/or gastrointestinal tract: stages II-IV.

    Measured: At day 84

  4. Relapse of Malignancy After Transplantation

    Defined by either morphological or cytogenetic evidence of acute leukemia consistent with pre-transplant features, or radiologic evidence of lymphoma progression. When in doubt, the diagnosis of recurrent or progressive lymphoma should be documented by tissue biopsy.

    Measured: Up to 7 years

Secondary outcomes (8)

  1. Time to Neutrophil Recovery

    Achievement of an absolute neutrophil count greater or equal to 500/mm^3 for three consecutive measurements on different days. The first of the three days will be designated the day of neutrophil recovery.

    Measured: Up to day 84 post-transplant

  2. Time to Platelet Recovery

    The first day of a sustained platelet count > 20,000/mm^3 with no platelet transfusions in the preceding seven days.

    Measured: Up to day 84 post-transplant

  3. Incidence of Primary Graft Failure

    Defined as < 5% donor CD3 chimerism. Chimerism will be measured by short tandem repeat-polymerase chain reaction on peripheral blood sorted into CD3 and CD33 cell fractions.

    Measured: At day 84

  4. Disease-free Survival

    Defined as being alive and in remission by < 5% blasts by bone marrow morphology for patients with myeloid malignancies and CT or PET imaging for patients with lymphoid malignancies at the time of the assessment

    Measured: 3 years from the date of transplant

  5. Toxicity of Treatment Regimen Determined by Number of Adverse Events Per Organ System

    Assessed by Common Terminology Criteria for Adverse Events version 3.0. The incidence of all adverse events greater or equal to grade 3 was determined.

    Measured: Up to day 90

  6. Number of Red Blood Cell Transfusions

    Number of units of RBCs given to the patient between day 0 and day 100 post transplant

    Measured: Day 0-100

  7. Number of Platelet Transfusions

    Number platelet transfusions given to the patient between day 0 and day 100 post transplant

    Measured: Day 0-100

  8. Point Estimate of Overall Survival at 3 Years

    Kaplan Meier estimate of the percentage of participants with overall survival at 3 years

    Measured: 3 years

Timeline

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

  1. First posted9 Dec 2009 (estimated)
  2. Study start19 May 2010
  3. Primary completion7 Oct 2021
  4. Study completion7 Oct 2021

Why it stopped: The study experienced lower accrual rates after the onset of COVID. Upon review of the collected data it was deemed that an adequate amount of subjects has been enrolled to date to assess study aims.

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01028716
Sponsor's protocol ID
2372.00
Other IDs
NCI-2009-01433, 2372, 2372.00, RG9213052
Status last verified
Jan 2023
First submitted
8 Dec 2009
Last updated
23 Jan 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cyclophosphamide, Filgrastim and Fludarabine Phosphate in people with Acute Biphenotypic Leukemia and Acute Erythroid Leukemia in Remission, run by Fred Hutchinson 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 42 inclusion and 5 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 23 Jan 2023. 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 23 Jan 2023). 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?

Non-relapse Mortality at 1 Year (time frame: Up to 1 year). The study lists 4 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 NCT01028716.

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 23 Jan 2023.

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