Clinical trial NCT00837200: Oncaspar/Doxil/Decadron in Patients With Refractory Lymphoid Malignancies
Official title: Phase II Pilot Efficacy Trial of the Combination Regimen Oncaspar/Doxil/Decadron (ODD) in Patients With Refractory Lymphoid Malignancies
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Non-hodgkins Lymphoma
Hodgkins Lymphoma
Multiple Myeloma
Keywords: lymphoma
myeloma
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
First posted: 2009-02-05
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an exploratory study to study the efficacy of combination regimen of Oncaspar/Doxil/Decadron (ODD) in patients with refractory lymphoid malignancies. Patients with any form of lymphoid malignancy will be eligible: acute lymphoblastic leukemia, chronic lymphocytic leukemia, non-Hodgkin's lymphoma, Hodgkin's lymphoma, multiple myeloma and plasma cell leukemia. Patients must have failed standard regimens for their cancers and could have had unlimited number of prior regimens. Patients will be staged appropriately for their disease with clinical examination, laboratory tests, and imaging studies. Both Oncaspar and Doxil will be given on day 1 and 15. Patients will be clinically evaluated prior to each cycle and will have disease assessments every 2 cycles. Responding patients will continue therapy until disease progression or excessive toxicity. Responders who are candidates for allogenic stem cell transplantation could go to conditioning chemotherapy and stem cell transplant after 4 cycles of ODD.

Detailed description: This phase II trial will study the effectiveness of a combination regimen which includes Oncaspar (PEG-asparaginase), Doxil (PEG-liposomal doxorubicin), and Decadron (ODD) in terms of disease response against refractory lymphoid malignancies. Asparaginase is an enzyme that depletes asparagines, a key amino acid for survival and growth of malignant lymphocytes. Its depletion results in death of the neoplastic cell. Asparagine depletion has induced a significant improvement of clinical outcomes in acute lymphoblastic leukemia (ALL) and L-asparaginase has been a mainstay for more than 30 years in the treatment of ALL. Although this drug has been used primarily in ALL, promising results have been reported even in other non-ALL lymphoid malignancies, such as chronic lymphocytic leukemia (CLL), prolymphocytic leukemia, refractory non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). One of the main goals of this trial is to measure the asparaginase level as a surrogate marker of asparagine depletion with Oncaspar, a PEG-enhanced version of E. coli L-asparaginase. The therapeutic value of the simple, non-pegylated form of L-asparaginase is limited by its short half-life and propensity to cause allergic reactions.

Eligibility criteria: Inclusion Criteria:

* Histologically documented lymphoid malignancies, regardless of their origin (B,T or NK). These include ALL, CLL, HL, NHL, MM and PCL.
* Patients must have failed at least one standard regimen of chemotherapy for their illness. They may have had unlimited prior regimens.
* Performance status of ≤ 2 as per ECOG scale.
* ALT \< 2.5 times the upper limit of normal
* Anticipated life expectancy of at least 12 weeks
* Patients will be allowed to have baseline cytopenias, but ANC should be \>200/μl and a platelet count \> 25,000/ μl (within 2 weeks of starting therapy).
* Patients must have a serum creatinine level ≤ 2 mg/dL (within 2 weeks of starting therapy).
* Male or female adults of at least 18 years of age.
* Signed written informed consent and willingness to meet follow-up schedule and study procedure obligations
* Left Ventricular Ejection Fraction (LVEF) \> 40% by echocardiogram or MUGA scan performed within 60 days prior to registration
* Women and men of childbearing potential must agree to employ adequate contraception to prevent pregnancy while on therapy.

Exclusion Criteria:

* Chemotherapy or radiotherapy received within the previous 2 weeks.
* Uncontrolled, active infection requiring IV antibiotics.
* Psychiatric illness that could potentially interfere with the completion of treatment according to this protocol.
* Pregnant or potential for pregnancy.
* Breast-feeding.
* Prior asparaginase therapy complicated by pancreatitis, allergic reaction, hemorrhagic event, or thrombosis
* Previous treatment with pegylated asparaginase
* Prior doxorubicin exposure, more than 400 mg/m2
* Clinically significant CHF
* No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for at least three years. Prior malignancy is acceptable provided there has been no evidence of disease within the three year interval.

Primary outcomes:
measure: Tumor Response
timeFrame: 16 weeks
measure: Study Specific Measure (Response)
timeFrame: 16 Weeks
measure: Study Specific Measure (Number of Participants Taken Off Study)
timeFrame: 16 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
Study officials:
affiliation: Penn State University
name: Joseph J. Drabick, MD
role: PRINCIPAL_INVESTIGATOR
References: