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Clofarabine and Low Dose Total Body Irradiation as a Preparative Regimen for Stem Cell Transplant in Leukemia.

Information source: Therapeutic Advances in Childhood Leukemia Consortium
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Leukemia Lymphoblastic, Acute; Acute Myeloid Leukemia; Neoplasm Recurrent

Intervention: Clofarabine (Drug); Total Body Irradiation (Radiation); Stem Cell Infusion (Other); Cyclosporins (Drug); Mycophenolate mofetil (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Therapeutic Advances in Childhood Leukemia Consortium

Official(s) and/or principal investigator(s):
Sandeep Soni, MD, Study Chair, Affiliation: Nationwide Childrens Hospital
Haydar Frangoul, MD, Study Chair, Affiliation: Vanderbilt University

Summary

Stem cell transplant is an important therapeutic option for pediatric patients with relapsed or refractory leukemia. Although, full myeloablative transplants are widely used for patients with acute leukemia, myeloablative chemo-radiotherapy may not be feasible in some specific settings. These settings include 1) patients with pre-existing health issues and organ toxicities; 2) patients who have relapsed post-ablative transplant and need a second stem cell transplant; and 3) leukemia patients with advanced disease who have been heavily pre-treated. Clofarabine, a new purine nucleoside anti-metabolite, has the advantage of significant antileukemic activity in addition to its possible immuno-suppressive properties. In this study we plan to determine the maximum feasible dose (MFD) of Clofarabine in combination with total body irradiation that can achieve durable donor engraftment without causing excessive toxicity.

Clinical Details

Official title: Phase I Feasibility Study of Clofarabine and Low Dose Total Body Irradiation (TBI) as a Non-myeloablative Preparative Regimen for Stem Cell Transplantation (SCT) for Hematologic Malignancies

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: To determine the maximum feasible dose of Clofarabine that can be given in combination with 2Gy total body irradiation as a non-myeloablative preparative regimen for allogeneic stem cell transplantation in pediatric patients with relapsed leukemia.

Secondary outcome:

To determine the rate of engraftment in both matched related donor (MRD) and matched unrelated donor (MUD) settings using this novel preparative regimen.

To assess the transplant related mortality (TRM) at day +100, associated with this non-myeloablative regimen.

Eligibility

Minimum age: 1 Year. Maximum age: 21 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Patients must be greater than or equal to 1 and less than or equal to 21 years of age

at the of study entry.

- Patients must have a diagnosis of ALL or AML.

- ALL patients must be in clinical remission defined as BM morphology <5% blasts and

CNS 1 status.

- AML patients must be in M1 (<5% blasts) or M2 (<20% blasts) marrow status with CNS 1

status.

- Patient must have an ANC greater than or equal to 750/ul.

- Patient must have one of the appropriate donor types as described below:

1. HLA identical sibling donor. 2. Complete matched unrelated donor, (matched at A, B, C, DR B1 and DQ, B1 at the allelic level based on high resolution typing for Class I and II antigens, 10/10 match). 3. 1 allelic mis-matched unrelated donor (antigen mis-matches are not allowed).

- The stem cell source from the donor must be one of the following:

1. Bone Marrow or Peripheral blood stem cells (PBSC) from a matched related donor. 2. PBSC from an unrelated donor. (Bone marrow is not acceptable for unrelated donors)

- Karnofsky > 50% for patients > 10 years of age and Lansky > 50% for patients less

than or equal to 10 years of age.

- Female patients of childbearing potential must have a negative serum pregnancy test

confirmed within 2 weeks prior to enrollment.

- Female patients with infants must agree not to breastfeed their infants while on this

study.

- Male and female patients of child-bearing potential must agree to use an effective

method of contraception approved by the investigator during the study.

- Patients must have a calculated creatinine clearance ≥ 70mL/min/m2 as calculated by

the Schwartz formula for estimated glomerular filtration rate (GFR) where GFR (ml/min/1. 73 m2) = k * Height (cm)/serum creatinine (mg/dl). K is a proportionality constant which varies with age and is a function of urinary creatinine excretion per unit of body size; 0. 45 up to 12 months of age; 0. 55 children and adolescent girls; and 0. 70 adolescent boys.

- Total serum bilirubin < 2 mg/dL.

- Aspartate transaminase (AST) and alanine transaminase (ALT) less than or equal to 5 ×

ULN.

- Patient must have a shortening fraction (SF) > 25%. If the SF is <25%, patient must

have an ejection fraction (EF) by MUGA of >30%.

- Patient must have pulmonary function as defined below:

1. DLCO >30% 2. FVC/TLC >30% 3. FEV1 > 30% of predicted 4. Patient is not on continuous oxygen If patient is not old enough or unable to comply with pulmonary function tests, they must have a pulse ox >92% in room air and not be on continuous oxygen.

- Patient must have signed informed consent

Exclusion Criteria:

- Patients will be excluded if they have evidence of an active, progressive invasive

infection. All patients with existing infections at the time study entry should be discussed with the study chair.

- Patients may have stable invasive infections and still be eligible.

- Patients with infections that are responsive to medical or surgical treatment as

shown by radiographic and or microbial assessment may still be eligible.

- Patients will be excluded if they have an active, uncontrolled systemic fungal,

bacterial, viral or other infection. All patients with existing infections at the time of study entry should be discussed with the study chair. •An active uncontrolled infection is defined as exhibiting ongoing signs and symptoms related to the infection (fevers, positive blood cultures, chills, tachycardia, etc) despite appropriate antibiotics or other treatment.

- Patient has a diagnosis of CML or MDS.

- Patient has CNS 2 or CNS 3 status.

- Patient is HIV positive.

- Current or planned treatment with chemotherapy, radiation therapy, or immunotherapy

other than as specified in the protocol.

- Use of investigational agents within 30 days or any anticancer therapy within 2 weeks

before study entry.

- Have any other severe concurrent disease, or have a history of serious organ

dysfunction or disease involving the heart, kidney (including dialysis patients), liver, or other organ system that may place the patient at undue risk to undergo treatment.

- Patients with a systemic fungal, bacterial, viral, or other infection not controlled

(defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).

- Any significant concurrent disease, illness, psychiatric disorder or social issue

that would compromise patient safety or compliance, study participation, follow up, or interpretation of study results.

Locations and Contacts

Childrens Hospital Los Angeles, Los Angeles, California 90027, United States

Nationwide Childrens Hospital, Columbus, Ohio, United States

Oregon Health and Science University, Portland, Oregon, United States

Vanderbilt Children's Hospital, Nashville, Tennessee, United States

Additional Information

Starting date: February 2010
Last updated: May 14, 2015

Page last updated: August 23, 2015

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