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Phase II Trial of Pentostatin, Cyclophosphamide, and Ofatumumab For Previously Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL)


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Hematopoietic/Lymphoid Cancer, B-cell Chronic Lymphocytic Leukemia, Contiguous Stage II Small Lymphocytic Lymphoma, Noncontiguous Stage II Small Lymphocytic Lymphoma, Stage 0 Chronic Lymphocytic Leukemia, Stage I Chronic Lymphocytic Leukemia, Stage I Small Lymphocytic Lymphoma, Stage II Chronic Lymphocytic Leukemia, Stage III Chronic Lymphocytic Leukemia, Stage III Small Lymphocytic Lymphoma, Stage IV Chronic Lymphocytic Leukemia, Stage IV Small Lymphocytic Lymphoma

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Trial Information

Phase II Trial of Pentostatin, Cyclophosphamide, and Ofatumumab For Previously Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL)


PRIMARY OBJECTIVES:

I. Arm A: To assess the rate of complete response using pentostatin, cyclophosphamide, and
ofatumumab in patients with previously untreated CLL or SLL requiring therapy.

II. Arm B: To assess the treatment-free survival rate at 18 months using
pentostatin,cyclophosphamide, and ofatumumab induction therapy followed by ofatumumab
consolidation in patients with previously untreated CLL or SSLL requiring therapy.

SECONDARY OBJECTIVES:

I. Arm A and Arm B: To assess the rate of overall response in patients with previously
untreated CLL or SLL requiring therapy and to determine the proportion of patients who
achieve a minimal residual disease (MRD) negative state as assessed by flow cytometry in
each arm independently.

II. Arm A and Arm B: To monitor and assess toxicity in patients with previously untreated
CLL or SLL in each arm independently.

III. Arm A and Arm B: To determine the progression-free survival, treatment-free survival,
and duration of response in each arm independently.

IV. Arm A and Arm B: To determine if molecular prognostic parameters (ZAP-70, CD38,
cytogenetic abnormalities identified by FISH, IgVH mutation status, etc) relate to response
to therapy in each arm independently.

V: Arm B: To assess the rate of complete response using pentostatin, cyclophosphamide, and
ofatumumab induction followed by ofatumumab consolidation in patients with previously
untreated CLL or SLL requiring therapy.

VI: Arm B: To evaluate whether consolidation therapy with ofatumumab after PCO induction
improves the depth of response.

OUTLINE: Patients receive ofatumumab IV on days 1-2 of course 1 and on day 1 of courses 2-6.
Patients also receive pentostatin IV over 30 minutes on day 1, cyclophosphamide IV over 30
minutes on day 1, and pegfilgrastim subcutaneously on day 2. Treatment repeats every 21 days
for 6 courses in the absence of disease progression or unacceptable toxicity. Patients on
Arm B receive additional courses with single agent ofatumumab IV on day 1 for 6 courses
(courses 7-12). Treatment repeats every 28 days in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

Inclusion Criteria


Inclusion

- Diagnosis of CLL according to the NCI criteria or SLL according to the WHO criteria,
including previous documentation of:

- a) Biopsy-proven small lymphocytic lymphoma (SLL) or

- b) Diagnosis of CLL according to NCI working group criteria as evidenced by ALL of
the following:

- 1) Peripheral blood lymphocyte count of > 5,000/mm^3 consisting of small to moderate
size lymphocytes, with < 55% prolymphocytes

- 2) Immunophenotyping consistent with CLL defined as: i) The predominant population of
lymphocytes share both B-cell antigens (CD19, CD20, or CD23) as well as CD5 in the
absence of other pan-T-cell markers (CD3, CD2, etc.); ii) Dim surface immunoglobulin
expression; iii) Restricted surface kappa or lambda light chain expression

- NOTE: Splenomegaly, hepatomegaly, or lymphadenopathy are not required for the
diagnosis of CLL

- 3) Before diagnosing CLL or SLL, mantle cell lymphoma must be excluded by
demonstrating a negative FISH analysis for t(11;14)(IgH/CCND1) on peripheral blood or
tissue biopsy or negative immunohistochemical stains for cyclin D1 on involved tissue
biopsy

- Patients must be previously untreated and meet at least one of the following
indications for chemotherapy:

- a) Evidence of progressive marrow failure as manifested by the development of or
worsening anemia (=< 11 g/dl) and/or thrombocytopenia (=< 100,000/mm^3) not due to
autoimmune disease

- b) Symptomatic or progressive lymphadenopathy, splenomegaly or hepatomegaly

- c) One or more of the following disease-related symptoms: 1) Weight loss > 10% within
the previous 6 months; 2) Extreme fatigue attributed to CLL; 3) Fevers > 100.5
degrees F for 2 weeks without evidence of infection; 4) Drenching night sweats
without evidence of infection

- d) Progressive lymphocytosis due to CLL with an increase of > 50% over a two month
period or an anticipated doubling time of less than six months

- NOTE: 1) Prior chemotherapy or monoclonal antibody based therapy for treatment of CLL
will be considered prior therapy; nutraceutical treatments with no established
benefit in CLL (such as epigallocatechin gallate or EGCG, found in green tea or other
herbal treatments) will not be considered prior treatment

- NOTE: 2) Marked hypogammaglobulinemia or the development of a monoclonal protein in
the absence of any of the above criteria for active disease are NOT sufficient for
protocol therapy

- The following laboratory values obtained =< 14 days prior to registration: serum
creatinine =< 1.5 x UNL; total bilirubin =< 1.5 x UNL unless due to Gilbert's disease
(if total bilirubin is > 1.5 x ULN, a direct bilirubin should be performed and must
be < 1.5 mg/dL for Gilbert's to be diagnosed); AST =< 3.0 x UNL and ALT =< 3.0 x UNL
(unless due to hemolysis or CLL)

- ECOG performance status (PS): 0, 1, or 2

- Willingness to provide blood samples as required

- Able to adhere to the study visit schedule and other protocol requirements

Exclusion

- Any of the following comorbid conditions: New York Heart Association Class III or IV
heart disease; recent myocardial infarction (< 1 month); uncontrolled infection;
infection with the human immunodeficiency virus (HIV/AIDS) as further severe
immunosuppression with this regimen may occur; infection with known chronic, active
Hepatitis B or C or Hepatitis B carriers

- Any of the following because this study involves an investigational agent whose
genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are
unknown: pregnant women; nursing women; men or women of childbearing potential who
are unwilling to employ adequate contraception

- Other active primary malignancy requiring treatment or limiting survival to =< 2
years

- Any radiation therapy =< 4 weeks prior to registration

- Any major surgery =< 4 weeks prior to registration

- Current use of corticosteroids (EXCEPTION: Low doses of steroids [< 10 mg of
prednisone or equivalent dose of other steroid] used for treatment of non-hematologic
medical conditions; NOTE: Previous use of corticosteroids is allowed)

- Active hemolytic anemia requiring immunosuppressive therapy or other pharmacologic
treatment; patients who have a positive Coombs test but no evidence of hemolysis are
NOT excluded from participation

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Arm A: Proportion of complete responses

Outcome Time Frame:

7 months

Safety Issue:

No

Principal Investigator

Tait Shanafelt, M.D.

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic

Authority:

United States: Food and Drug Administration

Study ID:

MC0983

NCT ID:

NCT01024010

Start Date:

August 2010

Completion Date:

Related Keywords:

  • Hematopoietic/Lymphoid Cancer
  • B-cell Chronic Lymphocytic Leukemia
  • Contiguous Stage II Small Lymphocytic Lymphoma
  • Noncontiguous Stage II Small Lymphocytic Lymphoma
  • Stage 0 Chronic Lymphocytic Leukemia
  • Stage I Chronic Lymphocytic Leukemia
  • Stage I Small Lymphocytic Lymphoma
  • Stage II Chronic Lymphocytic Leukemia
  • Stage III Chronic Lymphocytic Leukemia
  • Stage III Small Lymphocytic Lymphoma
  • Stage IV Chronic Lymphocytic Leukemia
  • Stage IV Small Lymphocytic Lymphoma
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Lymphoma

Name

Location

Mayo ClinicRochester, Minnesota  55905
Mayo Clinic in ArizonaScottsdale, Arizona  85259-5404
Mayo Clinic in FloridaJacksonville, Florida  32224
Duke University Medical CenterDurham, North Carolina  27710