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CompletedNCT01252667Updated Apr 16, 2020Results posted

Clofarabine and Low-Dose Total-Body Irradiation in Treating Patients With Acute Myeloid Leukemia Undergoing Donor Peripheral Blood Stem Cell Transplant

A Phase 2 interventional study of Allogeneic Hematopoietic Stem Cell Transplantation and Clofarabine in Acute Myeloid Leukemia, sponsored by Fred Hutchinson Cancer Center. Completed at 4 sites in United States. Open to participants aged 2 Years and older. Per ClinicalTrials.gov, last updated 2020-04-16.

Sponsored by Fred Hutchinson Cancer Center · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
44
Allocation
Non-randomized
Ages
2 Years and older
Sex
All
01

Study summary

This phase II trial studies the side effects and how well clofarabine works when given together with low-dose total-body irradiation (TBI) in treating patients with acute myeloid leukemia (AML) undergoing donor peripheral blood stem cell transplant (PBSCT). Giving chemotherapy and TBI before a donor PBSCT helps stop the growth of cancer cells. It may also 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.

Read the detailed description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose of clofarabine in combination with 2, 3, or 4 Gy TBI in preparation for hematopoietic cell transplantation (HCT) from human leukocyte antigen (HLA)-identical related and HLA-matched unrelated donors in patients with AML. (Part 1)

II. To determine the efficacy of the maximum tolerated dose of clofarabine combined with 2, 3, or 4 Gy TBI in reducing the 6 month relapse rate in patients with AML compared to our historical experience with fludarabine and 2 Gy TBI. A satisfactory improvement will be considered 6 month relapse rate declines from 35% to 20% among high-risk (objective for low risk group terminated August 2014). (Part 2)

SECONDARY OBJECTIVES:

I. Leukemia-free and overall survivals.

II. Non-relapse mortality (NRM) of \< 5% at 100 days.

III. Engraftment rate of >= 95%.

IV. Prognostic significance of cytogenetics and genetic markers not detected by traditional karyotype analysis, with special respect to tyrosine kinase receptor mutations (such as fms-like tyrosine kinase 3 [FLT3]), retrovirus-associated deoxyribonucleic acid (DNA) sequences (RAS)- and nucleophosmin gene mutations along with CCAAT/enhancer binding protein, alpha (C/EBP) mutations.

V. Rigorous monitoring for minimal residual/recurring disease by standard morphologic, flow cytometric, and molecular techniques in order to facilitate early intervention.

VI. To evaluate the pharmacokinetics of clofarabine (pharmacokinetic samples discontinued January 2017).

OUTLINE: This is a dose-escalation study of clofarabine.

CONDITIONING REGIMEN: Patients receive clofarabine intravenously (IV) over 2 hours on days -6 to -2. Patients also undergo TBI on day 0.

IMMUNOSUPPRESSION: Patients with related donors receive cyclosporine orally (PO) every 12 hours on days -3 to 56 with taper to day 180 and mycophenolate mofetil PO every 12 hours on days 0 to 28. Patients with unrelated donors receive cyclosporine PO every 12 hours on days -3 to 100 with taper to day 180 and mycophenolate mofetil PO every 8 hours on days 0 to 40 with taper to day 96.

TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0.

After completion of study treatment, patients are followed up at 4 months and then every year thereafter.

02

Conditions studied

  • Acute Myeloid Leukemia
03

In context

Leukemia

5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.

This study's enrollment of 44 is above the median of 38 across 4,247 interventional studies indexed under Leukemia.

Browse Leukemia studies →

Lead sponsor

Fred Hutchinson Cancer Center is the lead sponsor of 537 studies on the registry; 79 are open to participants now.

Of its 57 completed or terminated interventional studies of FDA-regulated products, 45 (79%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
2 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Patients age >= 55 years with AML OR patients age \< 55 years with AML, who also through pre-existing medical conditions or prior therapy are considered to be at high risk for serious toxicities associated with a conventional, high-dose preparative regimen
  • Patients must be in morphologic leukemia-free state (marrow blasts \< 5%) without evidence of extramedullary disease within 21 days of HCT
  • Only patients with Relapse Risk Score > 0 ("high risk") will be enrolled during Part 1; patients with all Relapse Risk Scores will be enrolled during Part 2 (low risk group terminated August 2014)
  • HLA-identical related or HLA-matched unrelated donor available
  • A signed informed consent form or minor assent form
  • DONOR: FHCRC matching allowed will be grade 1.0 to 2.1: unrelated donors who are prospectively: matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing; only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing
  • DONOR: A positive anti-donor cytotoxic crossmatch is an absolute donor exclusion; donors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment; this determination is based on the standard practice of the individual institution; the recommended procedure for patients with 10 of 10 HLA allele level (phenotypic) match is to obtain a panel reactive antibody (PRA) screens to class I and class II antigens for all patients before HCT; if the PRA shows > 10% activity, then flow cytometric or B and T cell cytotoxic cross matches should be obtained; the donor should be excluded if any of the cytotoxic cross match assays are positive; for those patients with an HLA Class I allele mismatch, flow cytometric or B and T cell cytotoxic cross matches should be obtained regardless of the PRA results
  • DONOR: Patient and donor pairs homozygous at a mismatched allele are considered a two-allele mismatch, i.e., the patient is A*0101 and the donor is A*0102, and this type of mismatch is not allowed
  • DONOR: Peripheral blood stem cells (PBSC) only will be permitted as a HSC source on this protocol

Exclusion criteria

Exclusion Criteria:

  • AML French-American-British (FAB) M3 in first complete remission (CR1)
  • Active AML involvement of the central nervous system (CNS) with disease refractory to intrathecal chemotherapy
  • Presence of circulating leukemic blasts in the peripheral blood detected by standard morphology
  • Patients who are human immunodeficiency virus (HIV)+ (HIV+ patients registered at Fred Hutchinson Cancer Research Center [FHCRC] should be offered treatment on Protocol 1410)
  • Fertile men and women unwilling to use contraceptive techniques during and for 12 months following treatment
  • Left ventricular ejection fraction \< 35% (or, if unable to obtain ejection fraction, shortening fraction of \< 26%); ejection fraction is required if age > 50 years or there is a history of anthracycline exposure or history of cardiac disease; patients with a shortening fraction \< 26% may be enrolled if approved by a cardiologist
  • Diffusion capacity of the lung for carbon monoxide (DLCO) \< 40% (corrected), total lung capacity (TLC) \< 40%, forced expiratory volume in one second (FEV1) \< 40% and/or receiving supplementary continuous oxygen
  • The FHCRC principal investigator (PI) of the study must approve enrollment of all patients with pulmonary nodules
  • Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bridging fibrosis, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, or symptomatic biliary disease
  • Serum creatinine should be within normal limits as specified by institutional guidelines; for patients with serum creatinine > upper limit of normal, a 24-hour creatinine clearance will be performed and should be equal to or more than the lower limit of normal
  • Karnofsky score \< 60 or Lansky score \< 50
  • Patients with poorly controlled hypertension and on multiple antihypertensives
  • Females who are pregnant or breastfeeding
  • Patients with active non-hematologic malignancies (except non-melanoma skin cancers) or those with non-hematologic malignancies (except non-melanoma skin cancers) who have been rendered with no evidence of disease, but have a greater than 20% chance of having disease recurrence within five years; this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy
  • The addition of cytotoxic agents for "cytoreduction" with the exception of tyrosine kinase inhibitors (such as imatinib mesylate), cytokine therapy, hydroxyurea, low dose cytarabine, chlorambucil, or Rituxan will not be allowed within three weeks of the initiation of conditioning
  • Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month
  • Patients with active bacterial or fungal infections unresponsive to medical therapy
  • DONOR: Marrow donors
  • DONOR: Donors who are HIV-positive and/or medical conditions that would result in increased risk to the donor filgrastim (G-CSF) mobilization and PBSC collections
  • DONOR: Identical twin
  • DONOR: Any contraindication to the administration of subcutaneous G-CSF at a dose of 16 mg/kg/day for 5 consecutive days
  • DONOR: Serious medical or psychological illness
  • DONOR: Pregnant or lactating females
  • DONOR: Prior malignancy within the preceding 5 years, with the exception of non-melanoma skin cancers
  • DONOR: Children \< 12 years old
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
44 participants (actual)

Study arms

  • Experimental
    Part 1 - Dose 1 (30 mg/m^2 Clofarabine)

    CONDITIONING REGIMEN: Patients receive 30 mg/m\^2 clofarabine IV over 2 hours on days -6 to -2. Patients also undergo TBI on day 0. IMMUNOSUPPRESSION: Patients with related donors receive cyclosporine PO every 12 hours on days -3 to 56 with taper to day 180 and mycophenolate mofetil PO every 12 hours on days 0 to 28. Patients with unrelated donors receive cyclosporine PO every 12 hours on days -3 to 100 with taper to day 180 and mycophenolate mofetil PO every 8 hours on days 0 to 40 with taper to day 96. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0. Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic hematopoietic PBSCT Clofarabine: Given IV Cyclosporine: Given PO Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Peripheral Blood Stem Cell Transplantation: Undergo allogeneic hematopoietic PBSCT Pharmacological Study: Optional correlative studies Total-Body Irradiation: Undergo TBI

    Procedure: Allogeneic Hematopoietic Stem Cell Transplantation · Drug: Clofarabine · Drug: Cyclosporine · Other: Laboratory Biomarker Analysis · Drug: Mycophenolate Mofetil · Procedure: Peripheral Blood Stem Cell Transplantation · Other: Pharmacological Study · Radiation: Total-Body Irradiation

  • Experimental
    Part 1 - Dose 2 (40 mg/m^2 Clofarabine)

    CONDITIONING REGIMEN: Patients receive 40 mg/m\^2 clofarabine IV over 2 hours on days -6 to -2. Patients also undergo TBI on day 0. IMMUNOSUPPRESSION: Patients with related donors receive cyclosporine PO every 12 hours on days -3 to 56 with taper to day 180 and mycophenolate mofetil PO every 12 hours on days 0 to 28. Patients with unrelated donors receive cyclosporine PO every 12 hours on days -3 to 100 with taper to day 180 and mycophenolate mofetil PO every 8 hours on days 0 to 40 with taper to day 96. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0. Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic hematopoietic PBSCT Clofarabine: Given IV Cyclosporine: Given PO Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Peripheral Blood Stem Cell Transplantation: Undergo allogeneic hematopoietic PBSCT Pharmacological Study: Optional correlative studies Total-Body Irradiation: Undergo TBI

    Procedure: Allogeneic Hematopoietic Stem Cell Transplantation · Drug: Clofarabine · Drug: Cyclosporine · Other: Laboratory Biomarker Analysis · Drug: Mycophenolate Mofetil · Procedure: Peripheral Blood Stem Cell Transplantation · Other: Pharmacological Study · Radiation: Total-Body Irradiation

  • Experimental
    Part 1 - Dose 3 (50 mg/m^2 Clofarabine)

    CONDITIONING REGIMEN: Patients receive 50 mg/m\^2 clofarabine IV over 2 hours on days -6 to -2. Patients also undergo TBI on day 0. IMMUNOSUPPRESSION: Patients with related donors receive cyclosporine PO every 12 hours on days -3 to 56 with taper to day 180 and mycophenolate mofetil PO every 12 hours on days 0 to 28. Patients with unrelated donors receive cyclosporine PO every 12 hours on days -3 to 100 with taper to day 180 and mycophenolate mofetil PO every 8 hours on days 0 to 40 with taper to day 96. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0. Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic hematopoietic PBSCT Clofarabine: Given IV Cyclosporine: Given PO Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Peripheral Blood Stem Cell Transplantation: Undergo allogeneic hematopoietic PBSCT Pharmacological Study: Optional correlative studies Total-Body Irradiation: Undergo TBI

    Procedure: Allogeneic Hematopoietic Stem Cell Transplantation · Drug: Clofarabine · Drug: Cyclosporine · Other: Laboratory Biomarker Analysis · Drug: Mycophenolate Mofetil · Procedure: Peripheral Blood Stem Cell Transplantation · Other: Pharmacological Study · Radiation: Total-Body Irradiation

  • Experimental
    Part 2 - Dose 1 (30 mg/m^2 Clofarabine)

    CONDITIONING REGIMEN: Patients receive 30 mg/m\^2 clofarabine IV over 2 hours on days -6 to -2. Patients also undergo TBI on day 0. IMMUNOSUPPRESSION: Patients with related donors receive cyclosporine PO every 12 hours on days -3 to 56 with taper to day 180 and mycophenolate mofetil PO every 12 hours on days 0 to 28. Patients with unrelated donors receive cyclosporine PO every 12 hours on days -3 to 100 with taper to day 180 and mycophenolate mofetil PO every 8 hours on days 0 to 40 with taper to day 96. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0. Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic hematopoietic PBSCT Clofarabine: Given IV Cyclosporine: Given PO Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Peripheral Blood Stem Cell Transplantation: Undergo allogeneic hematopoietic PBSCT Pharmacological Study: Optional correlative studies Total-Body Irradiation: Undergo TBI

    Procedure: Allogeneic Hematopoietic Stem Cell Transplantation · Drug: Clofarabine · Drug: Cyclosporine · Other: Laboratory Biomarker Analysis · Drug: Mycophenolate Mofetil · Procedure: Peripheral Blood Stem Cell Transplantation · Other: Pharmacological Study · Radiation: Total-Body Irradiation

  • Experimental
    Part 2 - Dose 2 (40 mg/m^2 Clofarabine)

    CONDITIONING REGIMEN: Patients receive 40 mg/m\^2 clofarabine IV over 2 hours on days -6 to -2. Patients also undergo TBI on day 0. IMMUNOSUPPRESSION: Patients with related donors receive cyclosporine PO every 12 hours on days -3 to 56 with taper to day 180 and mycophenolate mofetil PO every 12 hours on days 0 to 28. Patients with unrelated donors receive cyclosporine PO every 12 hours on days -3 to 100 with taper to day 180 and mycophenolate mofetil PO every 8 hours on days 0 to 40 with taper to day 96. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0. Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic hematopoietic PBSCT Clofarabine: Given IV Cyclosporine: Given PO Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Peripheral Blood Stem Cell Transplantation: Undergo allogeneic hematopoietic PBSCT Pharmacological Study: Optional correlative studies Total-Body Irradiation: Undergo TBI

    Procedure: Allogeneic Hematopoietic Stem Cell Transplantation · Drug: Clofarabine · Drug: Cyclosporine · Other: Laboratory Biomarker Analysis · Drug: Mycophenolate Mofetil · Procedure: Peripheral Blood Stem Cell Transplantation · Other: Pharmacological Study · Radiation: Total-Body Irradiation

  • Experimental
    Part 2 - Dose 3 (50 mg/m^2 Clofarabine)

    CONDITIONING REGIMEN: Patients receive 50 mg/m\^2 clofarabine IV over 2 hours on days -6 to -2. Patients also undergo TBI on day 0. IMMUNOSUPPRESSION: Patients with related donors receive cyclosporine PO every 12 hours on days -3 to 56 with taper to day 180 and mycophenolate mofetil PO every 12 hours on days 0 to 28. Patients with unrelated donors receive cyclosporine PO every 12 hours on days -3 to 100 with taper to day 180 and mycophenolate mofetil PO every 8 hours on days 0 to 40 with taper to day 96. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0. Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic hematopoietic PBSCT Clofarabine: Given IV Cyclosporine: Given PO Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Peripheral Blood Stem Cell Transplantation: Undergo allogeneic hematopoietic PBSCT Pharmacological Study: Optional correlative studies Total-Body Irradiation: Undergo TBI

    Procedure: Allogeneic Hematopoietic Stem Cell Transplantation · Drug: Clofarabine · Drug: Cyclosporine · Other: Laboratory Biomarker Analysis · Drug: Mycophenolate Mofetil · Procedure: Peripheral Blood Stem Cell Transplantation · Other: Pharmacological Study · Radiation: Total-Body Irradiation

Interventions

  • ProcedureAllogeneic Hematopoietic Stem Cell Transplantation

    Undergo allogeneic hematopoietic PBSCT

    Also known as: Allogeneic Hematopoietic Cell Transplantation, allogeneic stem cell transplantation, HSC, HSCT

  • DrugClofarabine

    Given IV

    Also known as: Clofarex, Clolar

  • DrugCyclosporine

    Given PO

    Also known as: 27-400, Ciclosporin, CsA, Cyclosporin, Cyclosporin A, Gengraf, Neoral, OL 27-400, Sandimmun, Sandimmune, SangCya

  • OtherLaboratory Biomarker Analysis

    Correlative studies

  • DrugMycophenolate Mofetil

    Given PO

    Also known as: Cellcept, MMF

  • ProcedurePeripheral Blood Stem Cell Transplantation

    Undergo allogeneic hematopoietic PBSCT

    Also known as: PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, peripheral stem cell support, Peripheral Stem Cell Transplant, peripheral stem cell transplantation

  • OtherPharmacological Study

    Optional correlative studies

  • RadiationTotal-Body Irradiation

    Undergo TBI

    Also known as: TOTAL BODY IRRADIATION, Whole-Body Irradiation

06

What researchers measure

Primary outcomes

  1. Part 1: Number of Participants With Dose Limiting Toxicities (DLT)

    The primary objective of part 1 is to determined the highest dose of clofarabine that can be tolerated safely in conjunction with nonmyeloablative transplant. If three patients successfully transplant without DLT, dose escalation occurs. If one of those three patients experiences DLT an additional three patients will be treated using the same dose. If a second DLT is observed in the first 3-6 patients, or if three patients are successfully transplanted without DLT at the highest dose the study will proceed to Part 2 using the maximum tolerated dose. A Clofarabine related dose-limiting toxicity is defined as a grade 4 toxicity involving the lungs, heart, liver (not resolving in 48 hours), kidneys (not resolving in 48 hours), gastrointestinal tract, and/or central nervous system.

    Time frame: 14 days post-transplant

  2. Part 2: Number of Participants With Relapsed Disease

    Number of high risk patients with relapsed disease after receiving the maximum dose of clofarabine. Relapse is defined as the presence of \>5% aberrant blasts by morphology on a marrow aspirate or the presence of circulating blasts in the peripheral blood.

    Time frame: 6 months post-transplant

Secondary outcomes

  1. Number of Participants Surviving Progression-free.

    Number of patients surviving without progressive disease post-transplant. Progression is defined as the presence of \>5% aberrant blasts by morphology on a marrow aspirate or the presence of circulating blasts in the peripheral blood.

    Time frame: 1 Year post-transplant

  2. Number of Participants Surviving Overall

    Number of patients surviving overall post-transplant.

    Time frame: 1 Year post-transplant

  3. Number of Non-Relapse Mortalities (NRM)

    Number of patients who expired without disease progression/relapse.

    Time frame: 100 days post-transplant

  4. Number of Participants Who Graft Rejected.

    Number of patients who graft rejected post-transplant. Graft rejection is defined as \<5% donor peripheral blood T cells (CD3+).

    Time frame: 1 Year post-transplant.

  5. Prognostic Significance of Cytogenetic and Genetic Markers

    Potential prognostic markers will be assessed by polymerase chain reaction (PCR) to determine their prognostic value.

    Time frame: 1 Year post-transplant

  6. Number of Participants With Minimal Residual/Recurring Disease (MRD) Post-transplant

    Number of patients with MRD post-transplant, detected in the bone marrow as cytogenetic abnormalities or \<5% monoclonal blasts by flow cytometry.

    Time frame: 1 Year post-transplant

  7. Pharmacokinetics (PK) of Clofarabine

    Pharmacokinetic measurement of the volume of plasma from which clofarabine is completely removed per unit time. Clearance normalized to actual body weight. Pharmacokinetic analyses were performed on only a subset of patients and no aggregate calculations were made using the data.

    Time frame: Blood was drawn on day -6 before the first clofarabine dosing, at the end of the infusion, and at 3, 4, 5, 6 and 24 hours after the start of infusion. Only pre-dose samples were drawn on days -5, -4, and -3.

07

Results

Posted Apr 16, 2020

Participant flow

Participant flow — Overall Study
MilestonePart 1 - Dose 1 (30 mg/m^2 Clofarabine)Part 1 - Dose 2 (40 mg/m^2 Clofarabine)Part 1 - Dose 3 (50 mg/m^2 Clofarabine)Part 2 - Dose 1 (30 mg/m^2 Clofarabine)Part 2 - Dose 2 (40 mg/m^2 Clofarabine)Part 2 - Dose 3 (50 mg/m^2 Clofarabine)
Started3330035
Completed3330034
Not completed000001
Withdrew: Transplant aborted post-conditioning000001

Outcome measures

PrimaryPart 1: Number of Participants With Dose Limiting Toxicities (DLT)

The primary objective of part 1 is to determined the highest dose of clofarabine that can be tolerated safely in conjunction with nonmyeloablative transplant. If three patients successfully transplant without DLT, dose escalation occurs. If one of those three patients experiences DLT an additional three patients will be treated using the same dose. If a second DLT is observed in the first 3-6 patients, or if three patients are successfully transplanted without DLT at the highest dose the study will proceed to Part 2 using the maximum tolerated dose. A Clofarabine related dose-limiting toxicity is defined as a grade 4 toxicity involving the lungs, heart, liver (not resolving in 48 hours), kidneys (not resolving in 48 hours), gastrointestinal tract, and/or central nervous system.

Time frame:
14 days post-transplant
Reported as:
Count of participants · Participants
Part 1: Number of Participants With Dose Limiting Toxicities (DLT)
ParticipantsPart 1 - Dose 1 (30 mg/m^2 Clofarabine)Part 1 - Dose 2 (40 mg/m^2 Clofarabine)Part 1 - Dose 3 (50 mg/m^2 Clofarabine)Part 2 - Dose 1 (30 mg/m^2 Clofarabine)Part 2 - Dose 2 (40 mg/m^2 Clofarabine)Part 2 - Dose 3 (50 mg/m^2 Clofarabine)
Part 1: Number of Participants With Dose Limiting Toxicities (DLT)000000
PrimaryPart 2: Number of Participants With Relapsed Disease

Number of high risk patients with relapsed disease after receiving the maximum dose of clofarabine. Relapse is defined as the presence of \>5% aberrant blasts by morphology on a marrow aspirate or the presence of circulating blasts in the peripheral blood.

Time frame:
6 months post-transplant
Reported as:
Count of participants · Participants
Part 2: Number of Participants With Relapsed Disease
ParticipantsPart 1 - Dose 1 (30 mg/m^2 Clofarabine)Part 1 - Dose 2 (40 mg/m^2 Clofarabine)Part 1 - Dose 3 (50 mg/m^2 Clofarabine)Part 2 - Dose 1 (30 mg/m^2 Clofarabine)Part 2 - Dose 2 (40 mg/m^2 Clofarabine)Part 2 - Dose 3 (50 mg/m^2 Clofarabine)
Part 2: Number of Participants With Relapsed Disease000003
SecondaryNumber of Participants Surviving Progression-free.

Number of patients surviving without progressive disease post-transplant. Progression is defined as the presence of \>5% aberrant blasts by morphology on a marrow aspirate or the presence of circulating blasts in the peripheral blood.

Time frame:
1 Year post-transplant
Reported as:
Count of participants · Participants
Number of Participants Surviving Progression-free.
ParticipantsPart 1 - Dose 1 (30 mg/m^2 Clofarabine)Part 1 - Dose 2 (40 mg/m^2 Clofarabine)Part 1 - Dose 3 (50 mg/m^2 Clofarabine)Part 2 - Dose 1 (30 mg/m^2 Clofarabine)Part 2 - Dose 2 (40 mg/m^2 Clofarabine)Part 2 - Dose 3 (50 mg/m^2 Clofarabine)
Number of Participants Surviving Progression-free.0210021
SecondaryNumber of Participants Surviving Overall

Number of patients surviving overall post-transplant.

Time frame:
1 Year post-transplant
Reported as:
Count of participants · Participants
Number of Participants Surviving Overall
ParticipantsPart 1 - Dose 1 (30 mg/m^2 Clofarabine)Part 1 - Dose 2 (40 mg/m^2 Clofarabine)Part 1 - Dose 3 (50 mg/m^2 Clofarabine)Part 2 - Dose 1 (30 mg/m^2 Clofarabine)Part 2 - Dose 2 (40 mg/m^2 Clofarabine)Part 2 - Dose 3 (50 mg/m^2 Clofarabine)
Number of Participants Surviving Overall0210022
SecondaryNumber of Non-Relapse Mortalities (NRM)

Number of patients who expired without disease progression/relapse.

Time frame:
100 days post-transplant
Reported as:
Count of participants · Participants
Number of Non-Relapse Mortalities (NRM)
ParticipantsPart 1 - Dose 1 (30 mg/m^2 Clofarabine)Part 1 - Dose 2 (40 mg/m^2 Clofarabine)Part 1 - Dose 3 (50 mg/m^2 Clofarabine)Part 2 - Dose 1 (30 mg/m^2 Clofarabine)Part 2 - Dose 2 (40 mg/m^2 Clofarabine)Part 2 - Dose 3 (50 mg/m^2 Clofarabine)
Number of Non-Relapse Mortalities (NRM)010001
SecondaryNumber of Participants Who Graft Rejected.

Number of patients who graft rejected post-transplant. Graft rejection is defined as \<5% donor peripheral blood T cells (CD3+).

Time frame:
1 Year post-transplant.
Reported as:
Count of participants · Participants
Number of Participants Who Graft Rejected.
ParticipantsPart 1 - Dose 1 (30 mg/m^2 Clofarabine)Part 1 - Dose 2 (40 mg/m^2 Clofarabine)Part 1 - Dose 3 (50 mg/m^2 Clofarabine)Part 2 - Dose 1 (30 mg/m^2 Clofarabine)Part 2 - Dose 2 (40 mg/m^2 Clofarabine)Part 2 - Dose 3 (50 mg/m^2 Clofarabine)
Number of Participants Who Graft Rejected.000000
SecondaryPrognostic Significance of Cytogenetic and Genetic Markers

Potential prognostic markers will be assessed by polymerase chain reaction (PCR) to determine their prognostic value.

Time frame:
1 Year post-transplant

No measurements were reported for this outcome.

SecondaryNumber of Participants With Minimal Residual/Recurring Disease (MRD) Post-transplant

Number of patients with MRD post-transplant, detected in the bone marrow as cytogenetic abnormalities or \<5% monoclonal blasts by flow cytometry.

Time frame:
1 Year post-transplant
Reported as:
Count of participants · Participants
Number of Participants With Minimal Residual/Recurring Disease (MRD) Post-transplant
ParticipantsPart 1 - Dose 1 (30 mg/m^2 Clofarabine)Part 1 - Dose 2 (40 mg/m^2 Clofarabine)Part 1 - Dose 3 (50 mg/m^2 Clofarabine)Part 2 - Dose 1 (30 mg/m^2 Clofarabine)Part 2 - Dose 2 (40 mg/m^2 Clofarabine)Part 2 - Dose 3 (50 mg/m^2 Clofarabine)
Number of Participants With Minimal Residual/Recurring Disease (MRD) Post-transplant020006
SecondaryPharmacokinetics (PK) of Clofarabine

Pharmacokinetic measurement of the volume of plasma from which clofarabine is completely removed per unit time. Clearance normalized to actual body weight. Pharmacokinetic analyses were performed on only a subset of patients and no aggregate calculations were made using the data.

Time frame:
Blood was drawn on day -6 before the first clofarabine dosing, at the end of the infusion, and at 3, 4, 5, 6 and 24 hours after the start of infusion. Only pre-dose samples were drawn on days -5, -4, and -3.
Reported as:
Number · L/h/kg
Pharmacokinetics (PK) of Clofarabine
L/h/kgPart 1 - Dose 1 (30 mg/m^2 Clofarabine)Part 1 - Dose 2 (40 mg/m^2 Clofarabine)Part 1 - Dose 3 (50 mg/m^2 Clofarabine)Part 2 - Dose 1 (30 mg/m^2 Clofarabine)Part 2 - Dose 2 (40 mg/m^2 Clofarabine)Part 2 - Dose 3 (50 mg/m^2 Clofarabine)
ID 1—0.53————
ID 2—0.37————
ID 4——0.29———
ID 5——0.40———
ID 6——0.50———

Adverse events

Collected over AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200; All-Cause Mortality: Conditioning through 1 Year.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Part 1 - Dose 1 (30 mg/m^2 Clofarabine)3/3 (100%)0/3 (0%)2/3 (66.7%)
Part 1 - Dose 2 (40 mg/m^2 Clofarabine)1/3 (33.3%)0/3 (0%)1/3 (33.3%)
Part 1 - Dose 3 (50 mg/m^2 Clofarabine)2/3 (66.7%)0/3 (0%)1/3 (33.3%)
Part 2 - Dose 1 (30 mg/m^2 Clofarabine)———
Part 2 - Dose 2 (40 mg/m^2 Clofarabine)———
Part 2 - Dose 3 (50 mg/m^2 Clofarabine)13/35 (37.1%)0/35 (0%)18/35 (51.4%)
Most frequent other events
Showing 10 of 29
Most frequent other events
EventPart 1 - Dose 1 (30 mg/m^2 Clofarabine)Part 1 - Dose 2 (40 mg/m^2 Clofarabine)Part 1 - Dose 3 (50 mg/m^2 Clofarabine)Part 2 - Dose 1 (30 mg/m^2 Clofarabine)Part 2 - Dose 2 (40 mg/m^2 Clofarabine)Part 2 - Dose 3 (50 mg/m^2 Clofarabine)
Acute kidney injuryRenal and urinary disorders0/31/30/3——0/35
Alanine aminotransferase increasedInvestigations0/30/31/3——3/35
AscitesGastrointestinal disorders0/31/30/3——0/35
Aspartate aminotransferase increasedInvestigations0/30/31/3——2/35
Atrial fibrillationCardiac disorders1/30/30/3——2/35
Blood bilirubin increasedInvestigations0/31/30/3——3/35
DiarrheaGastrointestinal disorders0/31/30/3——3/35
Febrile neutropeniaBlood and lymphatic system disorders0/31/30/3——3/35
GastroenteritisGastrointestinal disorders0/31/30/3——0/35
HypoxiaRespiratory, thoracic and mediastinal disorders1/30/30/3——1/35

Baseline characteristics

No subjects were treated with Dose 1 or 2 in Part 2 as no DLTs were observed in Part 1.

Age, Categorical
Age, Categorical(Participants)Part 1 - Dose 1 (30 mg/m^2 Clofarabine)Part 1 - Dose 2 (40 mg/m^2 Clofarabine)Part 1 - Dose 3 (50 mg/m^2 Clofarabine)Part 2 - Dose 1 (30 mg/m^2 Clofarabine)Part 2 - Dose 2 (40 mg/m^2 Clofarabine)Part 2 - Dose 3 (50 mg/m^2 Clofarabine)Total
<=18 years000——00
Between 18 and 65 years021——811
>=65 years312——2733
Age, Continuous
Age, Continuous(years)Part 1 - Dose 1 (30 mg/m^2 Clofarabine)Part 1 - Dose 2 (40 mg/m^2 Clofarabine)Part 1 - Dose 3 (50 mg/m^2 Clofarabine)Part 2 - Dose 1 (30 mg/m^2 Clofarabine)Part 2 - Dose 2 (40 mg/m^2 Clofarabine)Part 2 - Dose 3 (50 mg/m^2 Clofarabine)Total
Median73.4 (67.3 to 73.7)64.1 (59.9 to 67.1)67.7 (53.6 to 68.6)——69.5 (54.8 to 74.5)69.1 (53.6 to 74.5)
Sex: Female, Male
Sex: Female, Male(Participants)Part 1 - Dose 1 (30 mg/m^2 Clofarabine)Part 1 - Dose 2 (40 mg/m^2 Clofarabine)Part 1 - Dose 3 (50 mg/m^2 Clofarabine)Part 2 - Dose 1 (30 mg/m^2 Clofarabine)Part 2 - Dose 2 (40 mg/m^2 Clofarabine)Part 2 - Dose 3 (50 mg/m^2 Clofarabine)Total
Female111——1316
Male222——2228
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Part 1 - Dose 1 (30 mg/m^2 Clofarabine)Part 1 - Dose 2 (40 mg/m^2 Clofarabine)Part 1 - Dose 3 (50 mg/m^2 Clofarabine)Part 2 - Dose 1 (30 mg/m^2 Clofarabine)Part 2 - Dose 2 (40 mg/m^2 Clofarabine)Part 2 - Dose 3 (50 mg/m^2 Clofarabine)Total
Hispanic or Latino000——22
Not Hispanic or Latino333——3140
Unknown or Not Reported000——22
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Part 1 - Dose 1 (30 mg/m^2 Clofarabine)Part 1 - Dose 2 (40 mg/m^2 Clofarabine)Part 1 - Dose 3 (50 mg/m^2 Clofarabine)Part 2 - Dose 1 (30 mg/m^2 Clofarabine)Part 2 - Dose 2 (40 mg/m^2 Clofarabine)Part 2 - Dose 3 (50 mg/m^2 Clofarabine)Total
American Indian or Alaska Native000——00
Asian000——11
Native Hawaiian or Other Pacific Islander000——00
Black or African American000——00
White333——3241
More than one race000——00
Unknown or Not Reported000——22
Region of Enrollment
Region of Enrollment(participants)Part 1 - Dose 1 (30 mg/m^2 Clofarabine)Part 1 - Dose 2 (40 mg/m^2 Clofarabine)Part 1 - Dose 3 (50 mg/m^2 Clofarabine)Part 2 - Dose 1 (30 mg/m^2 Clofarabine)Part 2 - Dose 2 (40 mg/m^2 Clofarabine)Part 2 - Dose 3 (50 mg/m^2 Clofarabine)Total
United States333——3544
08

Study locations

4 sites
  • University of Colorado Hospital
    Aurora, Colorado 80045, United States
  • Ochsner Medical Center Jefferson
    New Orleans, Louisiana 70121, United States
  • VA Puget Sound Health Care System
    Seattle, Washington 98101, United States
  • Fred Hutch/University of Washington Cancer Consortium
    Seattle, Washington 98109, United States
09

References and documents

Publications

  • Krakow EF, Gyurkocza B, Storer BE, Chauncey TR, McCune JS, Radich JP, Bouvier ME, Estey EH, Storb R, Maloney DG, Sandmaier BM. Phase I/II multisite trial of optimally dosed clofarabine and low-dose TBI for hematopoietic cell transplantation in acute myeloid leukemia. Am J Hematol. 2020 Jan;95(1):48-56. doi: 10.1002/ajh.25665. Epub 2019 Nov 8. PubMed 31637757 ↗
  • Cooper JP, Storer BE, Granot N, Gyurkocza B, Sorror ML, Chauncey TR, Shizuru J, Franke GN, Maris MB, Boyer M, Bruno B, Sahebi F, Langston AA, Hari P, Agura ED, Lykke Petersen S, Maziarz RT, Bethge W, Asch J, Gutman JA, Olesen G, Yeager AM, Hubel K, Hogan WJ, Maloney DG, Mielcarek M, Martin PJ, Flowers MED, Georges GE, Woolfrey AE, Deeg JH, Scott BL, McDonald GB, Storb R, Sandmaier BM. Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades. Haematologica. 2021 Jun 1;106(6):1599-1607. doi: 10.3324/haematol.2020.248187. PubMed 32499241 ↗

Study documents

  • Protocol and statistical analysis plan · Sep 3, 2017

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 16, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01252667
Lead sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
Responsible party
Brenda Sandmaier (Principal Investigator, Fred Hutchinson Cancer Center) — Principal investigator
First posted
Dec 3, 2010
Start date
Jan 25, 2011
Primary completion
Jan 25, 2019
Completion
Mar 2019
Results posted
Apr 16, 2020
Last update
Apr 16, 2020

Study contacts

Brenda Sandmaier
principal investigator · Fred Hutch/University of Washington Cancer Consortium

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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