Clinical trial NCT00069966: Pixantrone, Cytarabine, Methylprednisolone, and Cisplatin in Treating Patients With Aggressive Non-Hodgkin's Lymphoma in First Relapse
Official title: A Phase II Trial of BBR 2778 in Combination With Cytarabine, Methylprednisolone and Cisplatin (BSHAP) as Salvage in Patients With Relapsed Aggressive Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Lymphoma
Keywords: recurrent adult diffuse large cell lymphoma
anaplastic large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult Burkitt lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-10-07
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as pixantrone, cytarabine, methylprednisolone, and cisplatin, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating patients who have relapsed aggressive non-Hodgkin's lymphoma.

Detailed description: OBJECTIVES:

* Determine the antitumor activity of pixantrone, cytarabine, methylprednisolone, and cisplatin in patients with aggressive non-Hodgkin's lymphoma in first relapse.
* Determine the safety and tolerability of this regimen in these patients.
* Determine the validity and safety of this regimen as a mobilization regimen before high-dose chemotherapy with stem cell support in these patients.

OUTLINE: This is an open-label, multicenter study.

* Salvage therapy: Patients receive pixantrone IV over 1 hour on day 1; cisplatin IV over 30 minutes on days 1-4; methylprednisolone IV over 15-30 minutes on days 1-5; and cytarabine IV over 2 hours on day 5. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.

After 2 courses of salvage therapy, patients are re-evaluated and treated as follows:

* Complete response (CR) or partial response (PR): Patients with a CR or PR who are suitable candidates for autologous stem cell transplantation (ASCT) proceed to mobilization therapy, high-dose chemotherapy, and ASCT. Patients with a CR or PR who are unsuitable candidates for ASCT continue to receive salvage therapy for up to 6 courses in the absence of disease progression or unacceptable toxicity.
* Stable disease: Patients with stable disease continue to receive salvage therapy for up to 6 courses. Patients who have a CR or PR after 3-4 courses of salvage therapy and who are suitable candidates for ASCT proceed to mobilization therapy, high-dose chemotherapy, and ASCT off study at the investigator's discretion.

  * Mobilization therapy (optional regimen; regimen used for mobilization is at the investigator's discretion): Patients receive rituximab\* IV on days 1 and 7; pixantrone IV over 1 hour on day 2; cisplatin IV over 30 minutes on days 2-5; cytarabine IV over 2 hours on day 6; and methylprednisolone IV over 15-30 minutes on days 2-6. Patients also receive filgrastim (G-CSF) subcutaneously once daily beginning on day 7 and continuing until blood counts recover. Patients receive 1 or more courses of mobilization therapy during which stem cells are harvested. Patients then proceed to high-dose chemotherapy and subsequent re-infusion of harvested stem cells.

NOTE: \*If this mobilization regimen is used, patients with T-cell lymphoma do not receive rituximab

* High-dose chemotherapy and ASCT: Patients receive high-dose chemotherapy and ASCT per institutional standard practice.

Patients are followed every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed aggressive non-Hodgkin's lymphoma (NHL)

  * Any stage, with or without B symptoms
  * The following subtypes are eligible:

    * Diffuse large cell (B and T cell types)
    * Anaplastic large cell
    * Diffuse mixed cell
    * Immunoblastic large cell
    * Follicular large cell
    * Transformed follicular NHL
    * Diffuse aggressive not otherwise classified
    * Burkitt-like lymphoma
* Bone marrow positive or negative
* At least 1 measurable lesion

  * Patients with bone marrow as the only site of disease are eligible without a measurable lesion
* No more than 1 episode of progressive disease, occurring after a response (complete response \[CR\], complete response unconfirmed \[CR_u\], or partial response \[PR\]) to prior chemotherapy\* NOTE: \*Patients with less than a CR, CRu, or PR and no progression, but who are good candidates for high-dose chemotherapy with stem cell support may be eligible (will be decided on an individual basis)
* No chemotherapy-refractory disease, defined as follows:

  * Stable or progressive disease documented at restaging immediately after the completion of induction therapy
* No lymphoblastic lymphoma, or mantle cell lymphoma

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* WHO 0-1

Life expectancy

* At least 3 months

Hematopoietic

* Neutrophil count at least 1,500/mm\^3\*
* Platelet count at least 100,000/mm\^3\* NOTE: \*Lower values may be accepted if clearly due to bone marrow involvement by lymphoma

Hepatic

* Bilirubin no greater than 1.5 times upper limit of normal (ULN)\*
* AST or ALT no greater than 2.0 times ULN\*
* Alkaline phosphatase no greater than 2.0 times ULN\*
* No history or clinical symptoms of hepatitis B or hepatitis C virus

  * Patients with seropositivity due to prior vaccination for hepatitis B are eligible NOTE: \*Higher values may be accepted if clearly due to liver involvement by lymphoma

Renal

* Creatinine no greater than 1.5 mg/dL

Cardiovascular

* LVEF at least 50% by MUGA
* No clinically significant cardiovascular abnormalities
* No New York Heart Association grade II-IV cardiovascular disease
* No myocardial infarction within the past 6 months
* No severe cardiac arrhythmia
* No uncontrolled hypertension

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 6 months after study participation
* HIV negative
* No clinically significant neurological abnormalities
* No condition that would preclude study safety or interfere with study results
* No concurrent serious uncontrolled infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Prior rituximab immediately after the first chemotherapy regimen allowed

Chemotherapy

* See Disease Characteristics
* See Biologic therapy
* At least 6 months since prior anthracycline therapy (e.g., cyclophosphamide, doxorubicin, vincristine, and prednisone \[CHOP\])
* More than 2 years since prior fludarabine
* More than 2 years since prior nitrosoureas
* More than 1 year since prior platinum-based chemotherapy or cytarabine, unless a CR or CR_u was achieved
* No prior cumulative dose of cisplatin greater than 600 mg/m\^2
* No prior single or cumulative dose of doxorubicin greater than 450 mg/m\^2

Endocrine therapy

* Not specified

Radiotherapy

* No prior radiotherapy to the whole pelvis
* No prior radioimmunotherapy

Surgery

* More than 4 weeks since prior major thoracic and/or abdominal surgery
* At least 1 week since prior minor surgery

Other

* Recovered from prior therapy

  * Alopecia allowed
  * Grade 1 peripheral neuropathy allowed
* More than 30 days since prior participation in another investigational drug study
* No other concurrent investigational drugs

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Oncology Associates - Craycroft Road Offices
state: Arizona
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Colorado Springs
country: United States
facility: Rocky Mountain Cancer Centers - Colorado Springs
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers - Denver Midtown
state: Colorado
city: Newark
country: United States
facility: Delaware Clinical & Laboratory Physicians
state: Delaware
city: New Port Richey
country: United States
facility: Pasco, Hernando Oncology Associates, P.A.
state: Florida
city: Chicago
country: United States
facility: Hematology-Oncology Associates of Illinois
state: Illinois
city: Lexington
country: United States
facility: Markey Cancer Center at University of Kentucky Chandler Medical Center
state: Kentucky
city: Shreveport
country: United States
facility: Louisiana State University Health Sciences Center - Shreveport
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
city: Omaha
country: United States
facility: UNMC Eppley Cancer Center at the University of Nebraska Medical Center
state: Nebraska
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Hospital
state: New York
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Piedmont Hematology-Oncology Associates
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center - Canton Office
state: Ohio
city: Cleveland
country: United States
facility: Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: Cancer Care Associates-West
state: Oklahoma
city: Portland
country: United States
facility: Providence Cancer Center at Providence Portland Medical Center
state: Oregon
city: Hershey
country: United States
facility: Penn State Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas - Eastside
state: South Carolina
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Fairfax Northern Virginia Hematology Oncology, P.C. - Fairfax
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
city: Hato Rey
country: Puerto Rico
facility: Hospital Auxilio Mutuo
Study officials:
affiliation: University of Nebraska
name: Julie M. Vose, MD
role: STUDY_CHAIR
References: