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Phase II Study of Clofarabine and High-Dose Melphalan Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation for Myelodysplasia or Acute Leukemia in Remission

Phase 2
18 Years
75 Years
Not Enrolling
Adult Acute Lymphoblastic Leukemia in Remission, Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), de Novo Myelodysplastic Syndromes, Previously Treated Myelodysplastic Syndromes, Secondary Acute Myeloid Leukemia

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Trial Information

Phase II Study of Clofarabine and High-Dose Melphalan Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation for Myelodysplasia or Acute Leukemia in Remission


I. Following a patient safety lead-in, determine the anti-tumor activity of clofarabine
given in combination with high-dose melphalan as assessed by 2-year progression-free
survival (PFS).

II. Estimate overall survival (OS), cumulative incidence (CI) of relapse/progression and
non-relapse mortality (NRM) at 100 days, 1 year and 2 years.

III. Summarize toxicities/complications by organ and severity, including acute and chronic
graft-vs-host disease (GVHD), and infection.


CONDITIONING REGIMEN: Patients receive clofarabine intravenously (IV) over 2 hours on days
-9 to -5 and melphalan IV over 30 minutes on day -4.

TRANSPLANT: Patients undergo allogeneic hematopoietic stem cell transplant on day 0.

GVHD PROPHYLAXIS: Beginning on day -3, patients receive tacrolimus IV or orally (PO) and
sirolimus PO once daily with taper beginning on day 100 or 180.

After completion of study treatment, patients are followed up on 30, 100, and 180 days; 1,
1.5, and 2 years; and then yearly for 3 years.

Inclusion Criteria:

- Patients in 1st or 2nd remission with acute myeloid leukemia (AML) or acute
lymphoblastic leukemia (ALL) (no circulating blasts, < 5% myeloblasts in the bone
marrow, normalization of previously detected cytogenetic abnormalities, no
extramedullary disease )

- High risk myelodysplastic syndrome (MDS) (not myeloproliferative neoplasms)

- Intermediate II and high risk by International Prognostic Scoring System (IPSS)

- Intermediate, high, or very high by World Health Organization (WHO)
classification-based Prognostic Scoring System (WPSS)

- Transfusion dependent

- Patients with MDS that has evolved to AML must be in remission

- Patient must not be eligible for full ablative regimens by the attending physician

- Performance status of >= 70% on the Karnofsky scale

- The effects of allogeneic transplantation on the developing fetus are highly toxic;
for this reason, women of child-bearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control or abstinence) prior to
study entry and for six months following duration of study participation; should a
woman become pregnant or suspect she is pregnant while participating on the trial,
she should inform her treating physician immediately

- Bone marrow and peripheral blood studies must be available for confirmation of
diagnosis; cytogenetics, flow cytometry, and molecular studies (such as Flt-3 status)
will be obtained as per standard practice

- Bone marrow aspirates/biopsies should be performed within 14 days from the start of
the conditioning regimen to confirm disease remission status

- Minimal residual disease will be assessed from pre-transplant and diagnostic (if
available) bone marrow aspirates by flow cytometry and Wilms' tumor suppressor gene
(WT1) polymerase chain reaction (PCR)

- A pretreatment measured creatinine clearance (absolute value of >= 60 mL/minute

- Patients must have a serum bilirubin =< 2.0 mg/dl

- Patients must have serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate
pyruvate transaminase (SGPT) =< 2.5 times the institutional upper limit of normal

- Ejection fraction measured by echocardiogram or multiple gated angiogram (MUGA) > 50%

- Diffusion capacity of carbon monoxide (DLCO) or forced expiratory volume in 1 second
(FEV1) > 45% predicted

- Availability of an HLA matched (6/6) sibling donor or 8/8 matched unrelated donor (no
mismatch allowed in HLA-A, HLA-B, HLA-C and HLA-DR, donors with mismatch HLA-DQ or
HLA-DPH are eligible)

- All patients must have a psychosocial evaluation prior to transplant as per City of
Hope (COH) standard operating procedure (SOP)

- All subjects must have the ability to understand and the willingness to sign a
written informed consent

- Patients who received chemotherapy (induction or consolidation) can proceed to
transplant once their counts have recovered (absolute neutrophil count [ANC] > 1000,
platelets > 100,000)

Exclusion Criteria:

- Patients who have received a prior autologous or allogeneic transplant are excluded

- Patients with significant hepatic dysfunction (not meeting liver function tests [LFT]
eligibility criteria in inclusion criteria)

- Patients with myelofibrosis or AML evolved from myelofibrosis

- Patients with MDS evolved into AML that is not in remission

- Patients with acute promyelocytic leukemia

- Patients with myeloproliferative neoplasms

- Patients with suspected or proven central nervous system (CNS) leukemia (diagnostic
lumbar puncture not required before enrollment)

- Uncontrolled intercurrent illness including, but not limited to ongoing or active or
poorly controlled infection, symptomatic congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, poorly controlled pulmonary disease or psychiatric
illness/social situations that would limit compliance with study requirements

- Pregnant or lactating women are excluded from this study

- Patients with immune deficiency are at increased risk of lethal infections when
treated with marrow-suppressive therapy; therefore, human immunodeficiency virus
(HIV)-positive patients are excluded from this study

- Patients who have received radiation therapy as part of their leukemia treatment may
be ineligible and individual cases must be presented to the principal investigator
(PI) for determination of eligibility

- Any psychiatric, social or compliance issues that, in the treating physician's
opinion, will interfere with completion of the transplant treatment and follow up

- Known allergies to clofarabine, melphalan, sirolimus or tacrolimus

- Patients with other active malignancies (besides AML, ALL, MDS) requiring treatment
or where there is concern of progression are ineligible for this study; however,
patients with previously treated skin cancer, early stage cervical or prostate cancer
may be eligible if there is no evidence of residual disease

- Cord blood as a donor source is not acceptable

- Subjects, who in the opinion of the investigator, may not be able to comply with the
safety monitoring requirements of the study

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival estimated from the start of treatment to the date of death, disease relapse/progression, or last follow-up, whichever comes first

Outcome Description:

Calculated using the Kaplan-Meier product-limit method.

Outcome Time Frame:

From the start of treatment to the date of death, assessed at 2 years

Safety Issue:


Principal Investigator

Samer Khaled

Investigator Role:

Principal Investigator

Investigator Affiliation:

City of Hope Medical Center


United States: Federal Government

Study ID:




Start Date:

December 2013

Completion Date:

Related Keywords:

  • Adult Acute Lymphoblastic Leukemia in Remission
  • Adult Acute Myeloid Leukemia in Remission
  • Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
  • Adult Acute Myeloid Leukemia With Del(5q)
  • Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
  • Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
  • de Novo Myelodysplastic Syndromes
  • Previously Treated Myelodysplastic Syndromes
  • Secondary Acute Myeloid Leukemia
  • Congenital Abnormalities
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia
  • Acute Disease



City of Hope Medical CenterDuarte, California  91010