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A Phase I/II Trial of Bendamustine/Treanda®, Rituximab, Etoposide, and Carboplatin for Patients With Relapsed or Refractory Lymphoid Malignancies and Select Untreated Lymphomas (TREC)


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Adult Grade III Lymphomatoid Granulomatosis, Adult Nasal Type Extranodal NK/T-cell Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Chronic Lymphocytic Leukemia, Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma, Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma, Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma, Contiguous Stage II Adult Lymphoblastic Lymphoma, Contiguous Stage II Grade 1 Follicular Lymphoma, Contiguous Stage II Grade 2 Follicular Lymphoma, Contiguous Stage II Grade 3 Follicular Lymphoma, Contiguous Stage II Mantle Cell Lymphoma, Contiguous Stage II Marginal Zone Lymphoma, Contiguous Stage II Small Lymphocytic Lymphoma, Cutaneous B-cell Non-Hodgkin Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Intraocular Lymphoma, Nodal Marginal Zone B-cell Lymphoma, Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma, Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma, Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma, Noncontiguous Stage II Adult Lymphoblastic Lymphoma, Noncontiguous Stage II Grade 1 Follicular Lymphoma, Noncontiguous Stage II Grade 2 Follicular Lymphoma, Noncontiguous Stage II Grade 3 Follicular Lymphoma, Noncontiguous Stage II Mantle Cell Lymphoma, Noncontiguous Stage II Marginal Zone Lymphoma, Noncontiguous Stage II Small Lymphocytic Lymphoma, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Grade III Lymphomatoid Granulomatosis, Recurrent Adult Hodgkin Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Mycosis Fungoides/Sezary Syndrome, Recurrent Small Lymphocytic Lymphoma, Small Intestine Lymphoma, Splenic Marginal Zone Lymphoma, Stage I Adult Burkitt Lymphoma, Stage I Adult Diffuse Mixed Cell Lymphoma, Stage I Adult Diffuse Small Cleaved Cell Lymphoma, Stage I Adult Immunoblastic Large Cell Lymphoma, Stage I Adult Lymphoblastic Lymphoma, Stage I Cutaneous T-cell Non-Hodgkin Lymphoma, Stage I Grade 1 Follicular Lymphoma, Stage I Grade 2 Follicular Lymphoma, Stage I Grade 3 Follicular Lymphoma, Stage I Mantle Cell Lymphoma, Stage I Marginal Zone Lymphoma, Stage I Mycosis Fungoides/Sezary Syndrome, Stage I Small Lymphocytic Lymphoma, Stage II Adult Burkitt Lymphoma, Stage II Cutaneous T-cell Non-Hodgkin Lymphoma, Stage II Grade 1 Follicular Lymphoma, Stage II Grade 2 Follicular Lymphoma, Stage II Grade 3 Follicular Lymphoma, Stage II Mycosis Fungoides/Sezary Syndrome, Stage III Adult Burkitt Lymphoma, Stage III Adult Diffuse Mixed Cell Lymphoma, Stage III Adult Diffuse Small Cleaved Cell Lymphoma, Stage III Adult Immunoblastic Large Cell Lymphoma, Stage III Adult Lymphoblastic Lymphoma, Stage III Cutaneous T-cell Non-Hodgkin Lymphoma, Stage III Grade 1 Follicular Lymphoma, Stage III Grade 2 Follicular Lymphoma, Stage III Grade 3 Follicular Lymphoma, Stage III Mantle Cell Lymphoma, Stage III Marginal Zone Lymphoma, Stage III Mycosis Fungoides/Sezary Syndrome, Stage III Small Lymphocytic Lymphoma, Stage IV Adult Burkitt Lymphoma, Stage IV Adult Diffuse Mixed Cell Lymphoma, Stage IV Adult Diffuse Small Cleaved Cell Lymphoma, Stage IV Adult Immunoblastic Large Cell Lymphoma, Stage IV Adult Lymphoblastic Lymphoma, Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma, Stage IV Grade 1 Follicular Lymphoma, Stage IV Grade 2 Follicular Lymphoma, Stage IV Grade 3 Follicular Lymphoma, Stage IV Mantle Cell Lymphoma, Stage IV Marginal Zone Lymphoma, Stage IV Mycosis Fungoides/Sezary Syndrome, Stage IV Small Lymphocytic Lymphoma, Waldenström Macroglobulinemia

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Trial Information

A Phase I/II Trial of Bendamustine/Treanda®, Rituximab, Etoposide, and Carboplatin for Patients With Relapsed or Refractory Lymphoid Malignancies and Select Untreated Lymphomas (TREC)


PRIMARY OBJECTIVES:

I. To estimate the maximally tolerated dose of bendamustine (bendamustine hydrochloride)
that can be combined with rituximab, carboplatin, and etoposide chemotherapy in patients
with relapsed or refractory lymphoid malignancies.

II. To determine the safety and toxicity of the above regimen.

SECONDARY OBJECTIVES:

I. To gain a preliminary assessment of the efficacy of the above regimen.

II. To determine the ability to proceed to peripheral blood stem cell collection following
the above regimen (the impact of above regimen on stem cell reserve).

III. To investigate whether findings from laboratory, radiographic or pathologic studies
have any prognostic impact on the response to treatment.

OUTLINE: This is a phase I, dose-escalation study of bendamustine hydrochloride followed by
a phase II study.

Patients receive bendamustine hydrochloride intravenously (IV) over 30-60 minutes on days 1
and 2, etoposide IV over 60 minutes on days 1-3, and carboplatin IV over 60 minutes on day
1. Patients with CD20+ T-cell lymphoma disease also receive rituximab IV on day 2 or 3.
Treatment repeats every 21 days for 2 courses in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment patients are followed up every 3 months for 1 year and
then every 6 months for 4 years.


Inclusion Criteria:



- Patients must have relapsed or primary refractory lymphomas: diffuse large B cell
lymphoma (DLBCL) or Hodgkin's lymphoma (HL); patients with other lymphoid
malignancies such as T- cell, or lymphomas that are not curable with anthracycline
based therapy (e.g. mantle cell lymphoma [MCL], follicular lymphoma [FL], marginal
zone lymphoma [MZL], lymphoplasmacytic lymphoma [LPL]) are eligible with protocol
Chair review and approval; note: the goal is to have a minimum of 20 patients with
DLBCL and 20 patients with HL

- World Health Organization (WHO) classification of patient's malignancies must be
provided

- Patients must have measurable disease defined as lesions that can be accurately
measured in two dimensions by computed tomography (CT), magnetic resonance imaging
(MRI), medical photograph (skin or oral lesion), plain x-ray, or other conventional
technique and a greatest transverse diameter of 1 cm or greater; or palpable lesions
with both diameters >= 2 cm; (Note: CT scans remain the standard for evaluation of
nodal disease)

- Patients must have a CT of chest, abdomen, and pelvis within 28 days of enrollment;
patients with evidence of lymphadenopathy in the neck must have a CT of neck

- Patients should not have evidence of active central nervous system lymphoma

- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0, 1, or 2

- Absolute neutrophil count (ANC) >= 1,500/mm^3 (without transfusion or growth factor
support); exception: patients with cytopenias due to disease, that do not meet these
criteria, will be considered eligible with review and approval by the principal
investigator (PI) or Co-PI prior to study entry

- Platelets >= 100,000/mm^3 (without transfusion or growth factor support); exception:
patients with cytopenias due to disease, that do not meet these criteria, will be
considered eligible with review and approval by the PI or Co-PI prior to study entry

- Serum creatinine < 1.5 mg/dl or creatinine clearance greater than 50/ ml per minute

- Total bilirubin < 1.5 times upper limit of normal

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 times upper
limit of normal

- Patients must have a serum lactate dehydrogenase (LDH) performed within 14 days prior
to registration

- All patients must be informed of the investigational nature of this study and have
given written consent in accordance with institutional and federal guidelines

- Patients must be anticipated to complete at least 2 cycles of chemotherapy

Exclusion Criteria:

- Patients known positive for human immunodeficiency virus (HIV), or infectious
hepatitis type B or C

- Pregnant or nursing women; men or women of reproductive potential may not participate
unless they have agreed to use an effective contraceptive method

- Patients with other prior malignancies except for adequately treated basal cell
carcinoma, squamous cell carcinoma of the skin, breast or cervical cancer in situ, or
other cancer from which the patient has been disease-free for 5 years or greater,
unless approved by the protocol Chair or Co-Chair

- Patients who are refractory (i.e. not responded or progressed within 6 months) to a
carboplatin, cisplatin, bendamustine, or etoposide-based regimen

- Patients who have other medical conditions that would contraindicate treatment with
aggressive chemotherapy (including active infection, uncontrolled hypertension,
congestive heart failure, unstable angina pectoris, or myocardial infarction within
the past 6 months, uncontrolled arrhythmia); if the patient's cardiac history is
questionable, a measurement of left ventricular ejection fraction should be obtained
within 42 days prior to registration; patients with left ventricular ejection
fraction < 50% are not eligible

- Autologous or allogeneic transplantation within 12 months or radioimmunotherapy
within 6 months of registration; prior failed (< 5x10^6 CD34/kg) peripheral blood
stem cell (PBSC) collection

- Patients who had pelvic radiation within 12 months or received more than 2 prior
therapies with myelotoxic regimens; single agent monoclonal antibody treatment is not
considered as one therapy; radiation treatment following chemotherapy is not
considered as one separated therapy; consolidative therapy will be considered one
regimen e.g. salvage therapy followed by conditioning regimen and transplant

- Previous chemotherapy/immunotherapy within 3 weeks before study entry

- Concurrent use of other anti-cancer agents or experimental treatments

- Known hypersensitivity to bendamustine, mannitol, etoposide, carboplatin, or
rituximab

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximally tolerated dose of bendamustine hydrochloride that can be combined with rituximab, carboplatin, and etoposide chemotherapy in patients with relapsed or refractory lymphoid malignancies

Outcome Description:

Defined as dose at which approximately =< 25% of patients experience a DLT. Following completed observation of final patient, two-parameter logistic model fit to data, generating dose-response curve based on observed toxicity rate at dose levels visited. Based on this fitted model, MTD is estimated to be dose that is associated with toxicity rate of 25%. If estimate of slope parameter for fitted curve is not positive and finite, geometric mean of dose level used for last cohort and dose level that would have been assigned to next cohort is taken as MTD.

Outcome Time Frame:

Up to 3-5 weeks after the last course

Safety Issue:

Yes

Principal Investigator

Ajay Gopal

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Institutional Review Board

Study ID:

PSOC 2502

NCT ID:

NCT01165112

Start Date:

September 2010

Completion Date:

Related Keywords:

  • Adult Grade III Lymphomatoid Granulomatosis
  • Adult Nasal Type Extranodal NK/T-cell Lymphoma
  • Anaplastic Large Cell Lymphoma
  • Angioimmunoblastic T-cell Lymphoma
  • Chronic Lymphocytic Leukemia
  • Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma
  • Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma
  • Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma
  • Contiguous Stage II Adult Lymphoblastic Lymphoma
  • Contiguous Stage II Grade 1 Follicular Lymphoma
  • Contiguous Stage II Grade 2 Follicular Lymphoma
  • Contiguous Stage II Grade 3 Follicular Lymphoma
  • Contiguous Stage II Mantle Cell Lymphoma
  • Contiguous Stage II Marginal Zone Lymphoma
  • Contiguous Stage II Small Lymphocytic Lymphoma
  • Cutaneous B-cell Non-Hodgkin Lymphoma
  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Intraocular Lymphoma
  • Nodal Marginal Zone B-cell Lymphoma
  • Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma
  • Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma
  • Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma
  • Noncontiguous Stage II Adult Lymphoblastic Lymphoma
  • Noncontiguous Stage II Grade 1 Follicular Lymphoma
  • Noncontiguous Stage II Grade 2 Follicular Lymphoma
  • Noncontiguous Stage II Grade 3 Follicular Lymphoma
  • Noncontiguous Stage II Mantle Cell Lymphoma
  • Noncontiguous Stage II Marginal Zone Lymphoma
  • Noncontiguous Stage II Small Lymphocytic Lymphoma
  • Recurrent Adult Burkitt Lymphoma
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Recurrent Adult Diffuse Mixed Cell Lymphoma
  • Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
  • Recurrent Adult Grade III Lymphomatoid Granulomatosis
  • Recurrent Adult Hodgkin Lymphoma
  • Recurrent Adult Immunoblastic Large Cell Lymphoma
  • Recurrent Adult Lymphoblastic Lymphoma
  • Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
  • Recurrent Grade 1 Follicular Lymphoma
  • Recurrent Grade 2 Follicular Lymphoma
  • Recurrent Grade 3 Follicular Lymphoma
  • Recurrent Mantle Cell Lymphoma
  • Recurrent Marginal Zone Lymphoma
  • Recurrent Mycosis Fungoides/Sezary Syndrome
  • Recurrent Small Lymphocytic Lymphoma
  • Small Intestine Lymphoma
  • Splenic Marginal Zone Lymphoma
  • Stage I Adult Burkitt Lymphoma
  • Stage I Adult Diffuse Mixed Cell Lymphoma
  • Stage I Adult Diffuse Small Cleaved Cell Lymphoma
  • Stage I Adult Immunoblastic Large Cell Lymphoma
  • Stage I Adult Lymphoblastic Lymphoma
  • Stage I Cutaneous T-cell Non-Hodgkin Lymphoma
  • Stage I Grade 1 Follicular Lymphoma
  • Stage I Grade 2 Follicular Lymphoma
  • Stage I Grade 3 Follicular Lymphoma
  • Stage I Mantle Cell Lymphoma
  • Stage I Marginal Zone Lymphoma
  • Stage I Mycosis Fungoides/Sezary Syndrome
  • Stage I Small Lymphocytic Lymphoma
  • Stage II Adult Burkitt Lymphoma
  • Stage II Cutaneous T-cell Non-Hodgkin Lymphoma
  • Stage II Grade 1 Follicular Lymphoma
  • Stage II Grade 2 Follicular Lymphoma
  • Stage II Grade 3 Follicular Lymphoma
  • Stage II Mycosis Fungoides/Sezary Syndrome
  • Stage III Adult Burkitt Lymphoma
  • Stage III Adult Diffuse Mixed Cell Lymphoma
  • Stage III Adult Diffuse Small Cleaved Cell Lymphoma
  • Stage III Adult Immunoblastic Large Cell Lymphoma
  • Stage III Adult Lymphoblastic Lymphoma
  • Stage III Cutaneous T-cell Non-Hodgkin Lymphoma
  • Stage III Grade 1 Follicular Lymphoma
  • Stage III Grade 2 Follicular Lymphoma
  • Stage III Grade 3 Follicular Lymphoma
  • Stage III Mantle Cell Lymphoma
  • Stage III Marginal Zone Lymphoma
  • Stage III Mycosis Fungoides/Sezary Syndrome
  • Stage III Small Lymphocytic Lymphoma
  • Stage IV Adult Burkitt Lymphoma
  • Stage IV Adult Diffuse Mixed Cell Lymphoma
  • Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
  • Stage IV Adult Immunoblastic Large Cell Lymphoma
  • Stage IV Adult Lymphoblastic Lymphoma
  • Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma
  • Stage IV Grade 1 Follicular Lymphoma
  • Stage IV Grade 2 Follicular Lymphoma
  • Stage IV Grade 3 Follicular Lymphoma
  • Stage IV Mantle Cell Lymphoma
  • Stage IV Marginal Zone Lymphoma
  • Stage IV Mycosis Fungoides/Sezary Syndrome
  • Stage IV Small Lymphocytic Lymphoma
  • Waldenström Macroglobulinemia
  • Burkitt Lymphoma
  • Hodgkin Disease
  • Immunoblastic Lymphadenopathy
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphomatoid Granulomatosis
  • Waldenstrom Macroglobulinemia
  • Mycoses
  • Mycosis Fungoides
  • Sezary Syndrome
  • Lymphoma, B-Cell
  • Lymphoma, Large-Cell, Immunoblastic
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Lymphoma, T-Cell
  • Lymphoma, T-Cell, Cutaneous
  • Lymphoma, Large-Cell, Anaplastic
  • Lymphoma, B-Cell, Marginal Zone
  • Lymphoma, Extranodal NK-T-Cell
  • Lymphoma, Mantle-Cell

Name

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109