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Graft Versus Host DiseasePhase 1/2NCT00423514

Clofarabine, Melphalan, and Thiotepa Followed By a Donor Stem Cell Transplant in Treating Patients With High-Risk and/or Advanced Hematologic Cancer or Other Disease

A Phase 1/2 study testing filgrastim, clofarabine and melphalan in people with Graft Versus Host Disease and Leukemia, run by Memorial Sloan Kettering 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

RATIONALE: Giving chemotherapy, such as clofarabine, melphalan, and thiotepa, before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Read more about this study

Who is it for?
Ages 0 to 54 years
What is being tested?
filgrastim, clofarabine and melphalan
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
1 siteUnited States
Study dates
20 Nov 2006to 18 Jun 2021
Phase
Phase 1/2
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 0 to 54 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed diagnosis of 1 of the following:
  • Acute myelogenous leukemia, meeting 1 of the following criteria:
  • In first complete remission (CR), meeting 1 of the following criteria:
  • Poor risk [no t(15,17), inv 16, or t(8,21)]
  • Not a candidate for total body irradiation (TBI)
  • Any infant in first CR
  • In second CR, meeting the following criteria:
  • All patients
  • In more than second CR OR relapsed/refractory disease, meeting the following criteria:
  • All patients
  • Blast percentage > 5% and < 25% in bone marrow (BM) at the time of stem cell transplantation (SCT)
  • Acute lymphoblastic leukemia, meeting 1 of the following criteria:
  • In first CR, meeting 1 of the following criteria:
  • Poor risk [t(9;22), t(4;11) AND no CR after 7-28 days of induction]
  • Not a candidate for TBI
  • Any infant in first CR
  • In second CR, meeting the following criteria:
  • All patients
  • In more than second CR OR relapsed/refractory disease, meeting the following criteria:
  • All patients
  • Blast percentage > 5% and < 25% in BM at the time of SCT
  • Acute undifferentiated or biphenotypic leukemia, meeting the following criteria:
  • All patients
  • Blast percentage > 5% and < 25% in BM at the time of SCT
  • Chronic myelogenous leukemia, meeting the following criteria:
  • All patients
  • In first chronic phase
  • Myelodysplastic syndrome, meeting 1 of the following criteria:
  • Primary high risk disease
  • Stage > RAEB1
  • Secondary high risk disease
  • All patients
  • Any stage
  • Juvenile myelomonocytic leukemia
  • All patients
  • No doubling of peripheral blast counts within a period of 2 weeks
  • No active CNS disease
  • HLA-compatible donor available meeting 1 of the following criteria:
  • Related donor
  • Genotypically or phenotypically matched at ≥ 7 or 8 of HLA-A, -B, -C and -DRB1 alleles
  • Unrelated donor meeting 1 of the following criteria:
  • 8 of 8 alleles matched
  • For patients < 18 years old only: 7 or 8 alleles matched with the mismatch at only 1 HLA-A, -B, -C, or -DRB1 allele
  • Two HLA-compatible unrelated cord blood (UCB) units available meeting the following criteria:
  • HLA-matched minimally at 4 of 6 HLA-A, HLA-B, and DRB1 allele
  • HLA-A and HLA-B matched at intermediate resolution by molecular technique
  • DRB1 allele matched at high resolution by molecular technique
  • Both matched UCB units with cryopreserved nucleated cell dose ≥ 1.5 x 10^7/kg

PATIENT CHARACTERISTICS:

  • Karnofsky OR Lansky performance status 70-100%
  • SGOT < 2 times upper limit of normal
  • Bilirubin < 1.5 mg/dL (unless there is liver disease involvement)
  • Creatinine normal OR creatinine clearance > 60 mL/min
  • LVEF > 50% at rest OR shortening fraction ≥ 29%
  • Patients with asymptomatic pulmonary disease with no prior risk factors OR symptomatic pulmonary disease with diffusion capacity > 50% of predicted (corrected for hemoglobin) are eligible
  • No active uncontrolled viral, bacterial, or fungal infection
  • No known HIV I or II positivity
  • No known human T-cell lymphotrophic virus I or II positivity
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

  • No hydroxyurea within the past 2 weeks
  • No allogeneic or autologous stem cell transplantation within the past 6 months

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: A Phase I/II Dose Escalation Trial of Clofarabine, in Addition to Melphalan and Thiotepa as Myeloablative Regimen Followed by an Allogeneic Unmodified Hematopoietic Stem Cell Transplant From HLA-Compatible Related or Unrelated Donors for the Treatment of High Risk and/or Advanced Hematologic Malignancies

RATIONALE: Giving chemotherapy, such as clofarabine, melphalan, and thiotepa, before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and mycophenolate mofetil before the transplant may stop this from happening.

PURPOSE: This phase I/II trial is studying the side effects and best dose of clofarabine when given together with melphalan and thiotepa, followed by a donor stem cell transplant and to see how well it works in treating patients with high-risk and/or advanced hematologic cancer or other disease.

Read the detailed description

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose of clofarabine when administered with melphalan and thiotepa followed by allogeneic stem cell transplantation in patients with high-risk and/or advanced hematologic malignancies. (Phase I)
  • Determine the 1-year disease-free survival of patients treated with this regimen. (Phase II)
  • Determine the efficacy of this regimen, in terms of antileukemic potential and relapse rate, in these patients.

Secondary

  • Evaluate the incidence and severity of nonhematologic toxicity of this regimen in these patients.
  • Evaluate the incidence and severity of graft-versus-host disease in patients treated with this regimen.

OUTLINE: This is a phase I, dose-escalation study of clofarabine followed by an open-label, phase II study. Patients are stratified according to HLA-compatible donor type (related vs unrelated).

  • Cytoreductive therapy: Patients receive clofarabine IV over 2 hours once daily on days -9 to -5, thiotepa IV over 4 hours on day -4, and melphalan IV over 30 minutes once daily on days -3 and -2.

Cohorts of 3-6 patients receive escalating doses of clofarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

  • Graft-versus-host disease (GVHD) prophylaxis: Patients who undergo bone marrow or peripheral blood stem cell transplantation receive tacrolimus IV continuously over 24 hours or orally every 8-12 hours beginning on day -3 and methotrexate IV on days 1, 3, 6, and 11. Patients who undergo UCB transplantation receive tacrolimus IV continuously over 24 hours or orally every 8-12 hours beginning on day -3 and mycophenolate mofetil (MMF) IV or orally 2 or 3 times daily on days -3 to 45 followed by a taper until day 100 (unless there are signs of acute GVHD). Patients who undergo UCB transplantation without GVHD continue tacrolimus for 6 months followed by a taper and discontinued 1 year after transplantation.
  • Allogeneic hematopoietic stem cell transplantation (HSCT) or allogeneic umbilical cord blood (UCB) transplantation: Patients undergo allogeneic HSCT (bone marrow or peripheral blood stem cells) or double UCB transplantation on day 0. Patients also receive filgrastim (G-CSF) IV or subcutaneously beginning on day 7 and continuing until blood counts recover.
  • Maintenance therapy: Approximately 2 months after transplantation patients with ALL, M4 or M5 AML, and those transplanted with AML in bone marrow relapse receive cytarabine intrathecally (IT) monthly for up to 5 doses. Patients with a history of CNS leukemia receive cytarabine IT once monthly during months 2-12 after HSCT.

After completion of study therapy, patients are followed periodically for at least 4 years.

PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.

Keywords
graft versus host disease, adult acute lymphoblastic leukemia in remission, adult acute myeloid leukemia in remission, childhood acute lymphoblastic leukemia in remission, childhood chronic myelogenous leukemia, recurrent childhood acute myeloid leukemia, accelerated phase chronic myelogenous leukemia, acute undifferentiated leukemia, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, blastic phase chronic myelogenous leukemia, juvenile myelomonocytic leukemia, previously treated myelodysplastic syndromes, recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, relapsing chronic myelogenous leukemia, secondary acute myeloid leukemia, secondary myelodysplastic syndromes, childhood acute myeloid leukemia in remission, de novo myelodysplastic syndromes, recurrent childhood acute lymphoblastic leukemia
Medical subject headings
Graft vs Host Disease, Leukemia, Myelodysplastic Syndromes, Leukemia, Myeloid, Accelerated Phase, Leukemia, Biphenotypic, Acute, Congenital Abnormalities, Blast Crisis, Leukemia, Myelomonocytic, Juvenile

What participants receive

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

Study groups in NCT00423514
Study groupRoleWhat they receive
cytoreduction regimen & stem cell transplantExperimentalThis is a single arm phase I/II clinical trial to assess efficacy (the antileukemic potential and relapse rate), and safety (peri-transplant morbidity and mortality) of a novel cytoreduction regimen in preparation for allogeneic hematopoietic stem cell transplantation (HSCT).
Receives: Biological: filgrastim; Drug: clofarabine; Drug: melphalan; Drug: mycophenolate mofetil; Drug: tacrolimus; Drug: thiotepa; Procedure: allogeneic bone marrow transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation

What is being measured

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

  1. Response to Therapy

    • A complete response (CR) will be defined as less than 5% bone marrow blasts in the setting of a neutrophil count of >/= 1.0 K/ul and a platelet count of >/= 75,000/ul
    • A complete response except platelets (CRp) will be defined as less than 5% bone marrow blasts in the setting of a neutrophil count of >/= 1.0 K/ul and a platelet count of >/= 75,000/ul
    • A partial response (PR) will be defined as 5%-25% bone marrow blasts in the setting of a neutrophil count of >/= 1.0 K/ul and a platelet count of >/= 75,000/ul
    • A partial response except platelets (PRp) will be defined as 5%-25% bone marrow blasts in the setting of a neutrophil count of >/= 1.0 K/ul and a platelet count of >/= 75,000/ul

    Measured: 1 year

  2. Overall Survival

    Measured: 1 year

Secondary outcomes (1)

  1. Participants Evaluated for Early Post-transplant Regimen-related Severe Morbidity (Grade III to IV Nonhematologic Toxicity) and Mortality as Measured by the NCI Cancer Therapy Evaluation Program CTCAE v 3.0

    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 posted18 Jan 2007 (estimated)
  2. Study start20 Nov 2006
  3. Primary completion18 Jun 2021
  4. Study completion18 Jun 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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00423514
Sponsor's protocol ID
06-125
Other IDs
MSKCC-06125
Status last verified
Jun 2021
First submitted
16 Jan 2007
Last updated
27 Dec 2022

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing filgrastim, clofarabine and melphalan in people with Graft Versus Host Disease and Leukemia, run by Memorial Sloan Kettering 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?

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 27 Dec 2022. 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 combined 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.

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 27 Dec 2022). 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?

Response to Therapy (time frame: 1 year). 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 NCT00423514.

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 27 Dec 2022.

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