Oncaspar/Doxil/Decadron in Patients With Refractory Lymphoid Malignancies

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Joseph Drabick, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier:
NCT00837200
First received: February 4, 2009
Last updated: August 1, 2014
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Non-hodgkins Lymphoma
Hodgkins Lymphoma
Multiple Myeloma
Drug: Oncaspar, Doxil, Decadron
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Pilot Efficacy Trial of the Combination Regimen Oncaspar/Doxil/Decadron (ODD) in Patients With Refractory Lymphoid Malignancies

Resource links provided by NLM:


Further study details as provided by Milton S. Hershey Medical Center:

Primary Outcome Measures:
  • Tumor Response [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
    • Leukemias mainly w/peripheral blood counts/diff every 2 wks/CLL, CT scan before initiation of study, 2nd CT after EOT, no CT at FU
    • Lymphomas restaged w/CT scans of chest/abdomen/pelvis or PET/CT scans after 2 cycles
    • MM monitored w/tumor markers monthly Quantitative immunoglobulins/SPEP w/quantitative M component in MM pts producing full antibody, UPEP w/ quantitative Bence-Jones in MM pts producing only light chains/Serum free light chains obtained all pts/Skeletal surveys at baseline Tumor responses:CR complete resolution of all detectable clinical/radiographic evidence of disease, disappearance of all disease related symptoms, and normalization of biochemical abnormalities for at least 6 wks following treatment and no BM infiltration;PR reduction of all measurable lesions by 50% or more/no new lesions;SD not fulfilling PR criteria/no evidence disease progression;PD increase original tumor mass by more than 25% lesion/new lesion
    • Stable disease > 2mo was a response

  • Study Specific Measure (Response) [ Time Frame: 16 Weeks ] [ Designated as safety issue: Yes ]
  • Study Specific Measure (Number of Participants Taken Off Study) [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 13
Study Start Date: March 2009
Study Completion Date: October 2013
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oncaspar, Doxil, Decadron Regimen
Once enrolled, patients will receive a cycle (28 days) of Oncaspar (2500 IU/m2 IV on days 1, 15; Doxil 20 mg/m2 IV days 1,15; and Decadron 20 mg PO days 1, 8, 15, 22. Continue until disease progression or unacceptable side effects.
Drug: Oncaspar, Doxil, Decadron
Once enrolled, patients will receive a cycle (28 days) of Oncaspar (2500 IU/m2 IV on days 1, 15; Doxil 20 mg/m2 IV days 1,15; and Decadron 20 mg PO days 1, 8, 15, 22. Continue until disease progression or unacceptable side effects.
Other Names:
  • PEG-asparaginase
  • PEG-liposomal doxorubicin

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00837200

Locations
United States, Pennsylvania
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17070
Sponsors and Collaborators
Milton S. Hershey Medical Center
Investigators
Principal Investigator: Joseph J. Drabick, MD Penn State University
  More Information

No publications provided

Responsible Party: Joseph Drabick, Professor of Medicine, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier: NCT00837200     History of Changes
Other Study ID Numbers: 08-007
Study First Received: February 4, 2009
Results First Received: May 2, 2014
Last Updated: August 1, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Milton S. Hershey Medical Center:
lymphoma
myeloma

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Liposomal doxorubicin
Pegaspargase
Asparaginase
Dexamethasone
Doxorubicin
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on September 14, 2014