Ofatumumab, Pentostatin, and Cyclophosphamide in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

• Register: ClinicalTrials.gov
• Last refreshed on: 3 December 2012
• Main ID: NCT01024010
• Date of registration: 01/12/2009
• Primary sponsor: Mayo Clinic
• Public title: Ofatumumab, Pentostatin, and Cyclophosphamide in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
• Scientific title: Phase II Trial of Pentostatin, Cyclophosphamide, and Ofatumumab For Previously Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL)
• Date of first enrolment: August 2010
• Target sample size: 82
• Recruitment status: Active, not recruiting
• URL: http://clinicaltrials.gov/show/NCT01024010
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Tait Shanafelt, M.D.
• Affiliation: Mayo Clinic

• Name: Han W. Tun, M.D.
• Affiliation: Mayo Clinic Florida

• Name: Jose Leis, M.D.
• Affiliation: Mayo Clinic in Arizona

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

B-cell Chronic Lymphocytic Leukemia

Contiguous Stage II Small Lymphocytic Lymphoma

Hematopoietic/Lymphoid Cancer

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

Intervention(s)

Biological: ofatumumab

Drug: cyclophosphamide

Drug: pentostatin

Genetic: protein expression analysis

Other: flow cytometry

Procedure: laboratory biomarker analysis

Primary Outcome(s)

Arm A: Proportion of complete responses [Time Frame: 7 months]

Arm B: Treatment-free Survival at 18 months [Time Frame: 18 months]

Secondary Outcome(s)

Adverse events [Time Frame: 24 months]

Complete response rate [Time Frame: 14 months]

Depth of response after ofatumumab consolidation [Time Frame: 14 months]

Differences in the distributions of risk factors (VH gene mutation, CD38, CD49d, ZAP-70 and FISH status) by clinical outcome (responders vs nonresponders) [Time Frame: 14 months]

Duration of response [Time Frame: 5 years]

Overall response rate [Time Frame: 14 months]

Progression-free survival [Time Frame: 5 years]

Treatment-free survival [Time Frame: 5 years]

Secondary ID(s)

09-003675

MC0983

NCI-2009-01437

OFT113301

Source(s) of Monetary Support

Please refer to primary and secondary sponsors