Pixantrone, Cytarabine, Methylprednisolone, and Cisplatin in Treating Patients With Aggressive Non-Hodgkin's Lymphoma in First Relapse

Sponsor

Theradex (Industry)

Overall Status

Unknown status

CT.gov ID

NCT00069966

Collaborator

(none)

Locations

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: filgrastim Biological: rituximab Drug: cisplatin Drug: cytarabine Drug: methylprednisolone Drug: pixantrone dimaleate Procedure: autologous bone marrow transplantation Procedure: peripheral blood stem cell transplantation	Phase 2

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.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Apr 1, 2003

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Oncology Associates - Craycroft Road Offices	Tucson	Arizona	United States	85712-2254
2	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010-3000
3	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California	United States	90033-0804
4	Rocky Mountain Cancer Centers - Colorado Springs	Colorado Springs	Colorado	United States	80933-1181
5	Rocky Mountain Cancer Centers - Denver Midtown	Denver	Colorado	United States	80218
6	Delaware Clinical & Laboratory Physicians	Newark	Delaware	United States	19713
7	Pasco, Hernando Oncology Associates, P.A.	New Port Richey	Florida	United States	34652
8	Hematology-Oncology Associates of Illinois	Chicago	Illinois	United States	60611-2998
9	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky	United States	40536-0084
10	Louisiana State University Health Sciences Center - Shreveport	Shreveport	Louisiana	United States	71130-3932
11	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
12	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
13	UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-7680
14	North Shore University Hospital	Manhasset	New York	United States	11030
15	SUNY Upstate Medical University Hospital	Syracuse	New York	United States	13210
16	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
17	Piedmont Hematology-Oncology Associates	Winston-Salem	North Carolina	United States	27103
18	Gabrail Cancer Center - Canton Office	Canton	Ohio	United States	44718
19	Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University	Cleveland	Ohio	United States	44106-5055
20	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
21	Cancer Care Associates-West	Oklahoma City	Oklahoma	United States	73112-4414
22	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon	United States	97213
23	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
24	Cancer Centers of the Carolinas - Eastside	Greenville	South Carolina	United States	29615
25	Baylor University Medical Center	Dallas	Texas	United States	75246
26	University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030
27	Fairfax Northern Virginia Hematology Oncology, P.C. - Fairfax	Fairfax	Virginia	United States	22031
28	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin	United States	53226-3596
29	Hospital Auxilio Mutuo	Hato Rey		Puerto Rico	00918