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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01024010
First received: December 1, 2009
Last updated: March 13, 2014
Last verified: March 2014
  Purpose

RATIONALE: Monoclonal antibodies, such as ofatumumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as pentostatin and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving ofatumumab together with pentostatin and cyclophosphamide may be a better way to block cancer growth.

PURPOSE: This phase II trial is studying how well giving ofatumumab together with pentostatin and cyclophosphamide works in treating patients with untreated chronic lymphocytic leukemia or small lymphocytic lymphoma.


Condition Intervention Phase
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
Drug: pentostatin
Drug: cyclophosphamide
Biological: ofatumumab
Procedure: laboratory biomarker analysis
Other: flow cytometry
Genetic: protein expression analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Pentostatin, Cyclophosphamide, and Ofatumumab For Previously Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL)

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Arm A: Proportion of complete responses [ Time Frame: 7 months ] [ Designated as safety issue: No ]
  • Arm B: Treatment-free Survival at 18 months [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall response rate [ Time Frame: 14 months ] [ Designated as safety issue: No ]
  • Complete response rate [ Time Frame: 14 months ] [ Designated as safety issue: No ]
  • Depth of response after ofatumumab consolidation [ Time Frame: 14 months ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Treatment-free survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Adverse events [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 82
Study Start Date: August 2010
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
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.
Drug: pentostatin
Given IV
Other Names:
  • 2'-deoxycoformycin
  • CI-825
  • co-vidarabine
  • DCF
  • deoxycoformycin
  • Nipent
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
  • Enduxan
Biological: ofatumumab
Given IV
Other Names:
  • Arzerra
  • HuMax-CD20
Procedure: laboratory biomarker analysis
Correlative study
Other: flow cytometry Genetic: protein expression analysis
Correlative study
Experimental: Arm B

Arm B: Experimental 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. Patients receive ofatumumab IV on day 1 of courses 7-12.

Interventions:

  • Drug: pentostatin
  • Drug: cyclophosphamide
  • Biological: ofatumumab
  • Procedure: laboratory biomarker analysis
  • Other: flow cytometry
  • Genetic: protein expression analysis
Drug: pentostatin
Given IV
Other Names:
  • 2'-deoxycoformycin
  • CI-825
  • co-vidarabine
  • DCF
  • deoxycoformycin
  • Nipent
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
  • Enduxan
Biological: ofatumumab
Given IV
Other Names:
  • Arzerra
  • HuMax-CD20
Procedure: laboratory biomarker analysis
Correlative study
Other: flow cytometry Genetic: protein expression analysis
Correlative study

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01024010

Locations
United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
United States, Florida
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224-9980
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Tait Shanafelt, M.D. Mayo Clinic
Principal Investigator: Jose Leis, M.D. Mayo Clinic in Arizona
Principal Investigator: Han W. Tun, M.D. Mayo Clinic Florida
  More Information

No publications provided by Mayo Clinic

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Tait D. Shanafelt, M.D., Mayo Clinic Cancer Center
ClinicalTrials.gov Identifier: NCT01024010     History of Changes
Other Study ID Numbers: MC0983, NCI-2009-01437, OFT113301, 09-003675, MC0983
Study First Received: December 1, 2009
Last Updated: March 13, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Cyclophosphamide
Pentostatin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Adenosine Deaminase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014