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Trial record 7 of 52 for:    "Acute Leukemia" | "Anti-Bacterial Agents"

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

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ClinicalTrials.gov Identifier: NCT01885689
Recruitment Status : Active, not recruiting
First Posted : June 25, 2013
Last Update Posted : October 10, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center

Tracking Information
First Submitted Date  ICMJE June 21, 2013
First Posted Date  ICMJE June 25, 2013
Last Update Posted Date October 10, 2019
Study Start Date  ICMJE January 8, 2014
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 31, 2014)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 21, 2013)
Progression-free survival estimated from the start of treatment to the date of death, disease relapse/progression, or last follow-up, whichever comes first [ Time Frame: From the start of treatment to the date of death, assessed at 2 years ]
Calculated using the Kaplan-Meier product-limit method.
Change History Complete list of historical versions of study NCT01885689 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 7, 2015)
  • 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.
  • Cumulative incidence of relapse/progression [ Time Frame: From start of treatment, assessed up to 5 years ]
    Calculated as competing risks using the Gray method.
  • 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.
  • 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.
  • 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.
  • 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.
  • Microbiologically documented infection [ Time Frame: Up to 100 days post-transplant ]
    Reported by site of disease, date of onset, severity and resolution, if any.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 21, 2013)
  • Overall survival [ Time Frame: From start of treatment until non-disease death, assessed up to 5 years ]
    Calculated using the Kaplan-Meier product-limit method.
  • Cumulative incidence of relapse/progression [ Time Frame: From start of treatment, assessed up to 5 years ]
    Calculated as competing risks using the Gray method.
  • Cumulative incidence of non-relapse mortality measured from start of treatment until non-disease-related death [ Time Frame: From start of treatment until non-disease death, assessed up to 5 years ]
    Calculated as competing risks using the Gray method.
  • Overall toxicity graded using the Bearman scale and CTCAE v4.0 [ 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.
  • 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.
  • 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.
  • Microbiologically documented infection [ Time Frame: Up to 100 days post-transplant ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Official Title  ICMJE Phase II Study of Clofarabine and High-Dose Melphalan Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation for Myelodysplasia or Acute Leukemia in Remission
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.
Detailed Description

PRIMARY OBJECTIVES:

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.

OUTLINE:

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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.

Interventions:
  • Drug: clofarabine
  • Drug: melphalan
  • Procedure: allogeneic hematopoietic stem cell transplantation
  • Drug: tacrolimus
  • Drug: sirolimus
  • Other: Pharmacological Study
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: June 21, 2013)
77
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01885689
Other Study ID Numbers  ICMJE 13130
NCI-2013-01193 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party City of Hope Medical Center
Study Sponsor  ICMJE City of Hope Medical Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Samer Khaled City of Hope Medical Center
PRS Account City of Hope Medical Center
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP