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Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01885689
Recruitment Status : Active, not recruiting
First Posted : June 25, 2013
Last Update Posted : February 18, 2022
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center

Brief Summary:
This phase II trial studies how well clofarabine and melphalan before a donor stem cell transplant works in treating patients with a decrease in or disappearance of signs and symptoms of myelodysplasia or acute leukemia (disease is in remission), or chronic myelomonocytic leukemia. Giving chemotherapy, such as clofarabine and melphalan, before a donor 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 the healthy stem cells from a donor are infused into a patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Giving clofarabine and melphalan before transplant may help prevent the cancer from coming back after transplant, and they may cause fewer side effects than standard treatment.

Condition or disease Intervention/treatment Phase
Adult Acute Lymphoblastic Leukemia in Remission Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome Adult Acute Myeloid Leukemia in Remission Myelodysplastic Syndrome Secondary Myelodysplastic Syndrome Chronic Myelomonocytic Leukemia Therapy-Related Myelodysplastic Syndrome Drug: clofarabine Drug: melphalan Procedure: allogeneic hematopoietic stem cell transplantation Drug: tacrolimus Drug: sirolimus Other: Pharmacological Study Phase 2

Detailed Description:


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 per City of Hope standard operating procedure.

After completion of study treatment, patients are followed up once weekly for 60 days, at 100, and 180 days, at one year, and then yearly for up to 5 years.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 77 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Clofarabine and High-Dose Melphalan Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation for Myelodysplasia or Acute Leukemia in Remission
Actual Study Start Date : February 10, 2014
Estimated Primary Completion Date : December 30, 2022
Estimated Study Completion Date : December 30, 2022

Arm Intervention/treatment
Experimental: Treatment (clofarabine, melphalan, transplant)

CONDITIONING REGIMEN: Patients receive clofarabine 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 PO and sirolimus PO once daily with taper per City of Hope standard operating procedure.

Drug: clofarabine
Given IV
Other Names:
  • CAFdA
  • Clofarex
  • Clolar

Drug: melphalan
Given IV
Other Names:
  • Alkeran
  • CB-3025
  • L-PAM
  • L-phenylalanine mustard
  • L-Sarcolysin

Procedure: allogeneic hematopoietic stem cell transplantation
Undergo allogeneic hematopoietic stem cell transplant

Drug: tacrolimus
Given IV or PO
Other Names:
  • FK 506
  • Prograf

Drug: sirolimus
Given PO
Other Names:
  • AY 22989
  • Rapamune
  • rapamycin
  • SLM

Other: Pharmacological Study
Correlative studies

Primary Outcome Measures :
  1. Progression-free survival [ Time Frame: From start of treatment to the date of death, disease relapse/progression, or last follow-up whichever occurs first, assessed at 2 years ]
    Calculated using the Kaplan-Meier product-limit method.

Secondary Outcome Measures :
  1. Overall survival [ Time Frame: From start of treatment until death, or last follow-up, whichever comes first, assessed up to 5 years ]
    Calculated using the Kaplan-Meier product-limit method.

  2. Cumulative incidence of relapse/progression [ Time Frame: From start of treatment, assessed up to 5 years ]
    Calculated as competing risks using the Gray method.

  3. Cumulative incidence of non-relapse mortality defined as death occurring in a patient from causes other than relapse or progression [ Time Frame: From start of treatment until non-disease death, assessed up to 5 years ]
    Calculated as competing risks using the Gray method.

  4. Overall toxicity graded using the Bearman scale and CTCAE v4.03 [ Time Frame: Up to 100 days post-transplant ]
    Toxicity information recorded will include the type, severity, and the probable association with the study regimen. Tables will be constructed to summarize the observed incidence by severity and type of toxicity.

  5. Incidence and severity of acute GVHD of grades 2-4 and 3-4 according to the consensus grading [ Time Frame: Up to 100 days post-transplant ]
    The first day of acute GVHD onset at a certain grade will be used to calculate cumulative incidence curves for that GVHD grade.

  6. Incidence and severity of chronic GVHD scored according to National Institute of Health (NIH) consensus staging [ Time Frame: After 100 days post-transplant ]
    The first day of chronic GVHD onset will be used to calculate cumulative incidence curves.

  7. Microbiologically documented infection [ Time Frame: Up to 100 days post-transplant ]
    Reported by site of disease, date of onset, severity and resolution, if any.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients in 1st or 2nd remission with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), who are eligible for stem cell transplant. Remission defined as no circulating blasts, < 5% blasts in the bone marrow, normalization of previously detected cytogenetic abnormalities, no extramedullary disease
  • High risk myelodysplastic syndrome (MDS)

    • 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
    • Therapy-related MDS or MDS evolved from previous hematological disorder (excepting myelofibrosis)
  • Patients with chronic myelomonocytic leukemia (CMML) are allowed to be enrolled
  • Patients with MDS that has evolved to AML must be in remission
  • Patients must not be eligible for full ablative regimens by the attending physician
  • Patients with AML or MDS arising from myeloproliferative neoplasm can be enrolled after principal investigator (PI) approval on case to case basis, depends on the spleen size and degree of bone marrow fibrosis
  • Performance status of >= 70% on the Karnofsky scale
  • 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 28 (+ 4 day window) days from registration to confirm disease remission status
  • 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 multi gated acquisition scan (MUGA) > 50%
  • Diffusing capacity of the lung for carbon monoxide (DLCO) or forced expiratory volume in 1 second (FEV1) > 45% predicted
  • Availability of a human leukocyte antigen (HLA) matched (6/6) sibling donor or 8/8 matched unrelated donor; Donors with mismatch at HLA-A, HLA-B, HLA-C, and HLA-DR will be reviewed by matched unrelated donor (MUD) committee and allowed if their mismatch with the recipient does not require additional GVHD prophylaxis (other than tacrolimus and sirolimus), donors with mismatch at HLA-DQ or HLA-DPB are eligible; donor evaluation according to City of Hope (COH) standard operating procedure (SOP)
  • Donor stem cell source can be either peripheral blood or bone marrow
  • All patients must have a psychosocial evaluation prior to transplant as per COH SOP
  • All subjects must have the ability to understand and the willingness to sign a written informed consent
  • ALL or AML patients who received chemotherapy (induction or consolidation) can proceed to transplant once bone marrow cellularity is > 10 % with no evidence of leukemia

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)
  • 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 and lactating women are excluded from this study
  • Patients who do not agree to practice effective forms of contraception
  • Human immunodeficiency virus (HIV)-positive patients are excluded from this study
  • Patients are excluded if they are hepatitis B surface antigen (sAg), hepatitis B (Hep B) core antibody (cAb), or hepatitis C (Hep C) positive. Patients with Hepatitis B cAB positive and Hepatitis B PCR negative are eligible if they started prophylactic treatment prior to registration to trial
  • Patients who have received radiation therapy as part of their leukemia treatment may be ineligible and individual cases must be presented to the study 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
  • Medical or psychiatric reasons which make the donor unlikely to tolerate or cooperate with filgrastim (G-CSF) therapy or leukapheresis or bone marrow harvest
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01885689

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United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
Sponsors and Collaborators
City of Hope Medical Center
National Cancer Institute (NCI)
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Principal Investigator: Samer Khaled City of Hope Medical Center
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Responsible Party: City of Hope Medical Center Identifier: NCT01885689    
Other Study ID Numbers: 13130
NCI-2013-01193 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Posted: June 25, 2013    Key Record Dates
Last Update Posted: February 18, 2022
Last Verified: February 2022
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Myelodysplastic Syndromes
Pathologic Processes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myelodysplastic-Myeloproliferative Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs