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

NCT01024010 | Completed Phase 2 Results DMC

• 3 other identifiers: MC0983NCI-2009-01437P30CA015083
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 4

Brief Summary

This phase II trial studies how well giving ofatumumab together with pentostatin and cyclophosphamide works in treating patients with untreated chronic lymphocytic leukemia or small lymphocytic lymphoma. Monoclonal antibodies, such as ofatumumab, can block the ability of cancer cells to grow and spread. 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, by stopping them from dividing, or by stopping them from spreading. Giving ofatumumab together with pentostatin and cyclophosphamide may be a better way to block cancer growth.

Conditions

Chronic Lymphocytic Leukemia; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Small Lymphocytic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (2)

• Arm A: Percentage of Complete Responses

  In Arm A: PCO, the primary endpoint of this trial is the percentage of complete responses. The NCI Working Group criteria was used to assess response to therapy: A Complete Response (CR) is briefly defines as the absence of lymphadenopathy, no heptomegaly nor splenomegaly, neutrophils greater than 1500/ul, platelets \> 100,000/ul, hemoglobin \>11.0 gm/dl, and peripheral blood lymphocytes \<4000uL.

  7 months

• Arm B: Treatment-free Survival at 18 Months

  The primary endpoint Arm B: PCO+O is treatment-free survival rate at 18 months. An event for treatment-free survival will be defined as initiation of subsequent therapy for CLL or death due to any cause. All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be evaluable for event-free survival at 18 months. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportion will be calculated.

  18 months

Secondary Outcomes (3)

• Overall Response Rate

  14 months

• Depth of Response After Ofatumumab Consolidation

  14 months

• Treatment-free Survival

  up to 5 years from registration

Study Arms (2)

Arm A (PCO, closed to accrual as of 8/23/2011)

EXPERIMENTAL

Patients receive induction therapy comprising ofatumumab IV on day 1 (days 1-2 of course 1 only), pentostatin IV over 30 minutes on day 1, and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: Cyclophosphamide; Other: Laboratory Biomarker Analysis; Biological: Ofatumumab; Drug: Pentostatin

Arm B (PCO with ofatumumab consolidation)

EXPERIMENTAL

Patients receive induction therapy as in Arm A. Patients then receive consolidation therapy comprising ofatumumab IV on day 1. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: Cyclophosphamide; Other: Laboratory Biomarker Analysis; Biological: Ofatumumab; Drug: Pentostatin

Interventions

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Arm A (PCO, closed to accrual as of 8/23/2011); Arm B (PCO with ofatumumab consolidation)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm A (PCO, closed to accrual as of 8/23/2011); Arm B (PCO with ofatumumab consolidation)

Ofatumumab BIOLOGICAL

Given IV

Also known as: Arzerra, GSK1841157, HuMax-CD20, HuMax-CD20, 2F2

Arm A (PCO, closed to accrual as of 8/23/2011); Arm B (PCO with ofatumumab consolidation)

Pentostatin DRUG

Given IV

Also known as: (R)-3-(2-Deoxy-.beta.-D-erythro-pentofuranosyl)-3,6,7, 8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol, 2'-Deoxycoformycin, CI-825, Co-Vidarabine, Covidarabine, DCF, Deoxycoformycin, Nipent, PD-81565, Pentostatine

Arm A (PCO, closed to accrual as of 8/23/2011); Arm B (PCO with ofatumumab consolidation)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of CLL according to the National Cancer Institute (NCI) criteria or SLL according to the World Health Organization (WHO) criteria, including previous documentation of:
• Biopsy-proven SLL
• Diagnosis of CLL according to NCI working group criteria as evidenced by all of the following:
• Peripheral blood lymphocyte count of \> 5,000/mm\^3 consisting of small to moderate size lymphocytes, with \< 55% prolymphocytes
• Immunophenotyping consistent with CLL defined as:
• The predominant population of lymphocytes share both B-cell antigens (CD19, CD20 \[typically dim expression\], or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc.)
• Clonality as evidenced by kappa or lambda light chain expression (typically dim immunoglobulin expression)
• Note: splenomegaly, hepatomegaly, or lymphadenopathy are not required for the diagnosis of CLL
• Before diagnosing CLL or SLL, mantle cell lymphoma must be excluded by demonstrating a negative FISH analysis for t(11;14)(immunoglobulin heavy \[IgH\]/cyclin D1 \[CCND1\]) on peripheral blood or tissue biopsy or negative immunohistochemical stains for CCND1 on involved tissue biopsy
• Patients must be previously untreated and meet at least one of the following indications for chemotherapy:
• 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
• Symptomatic or progressive lymphadenopathy, splenomegaly or hepatomegaly
• One or more of the following disease-related symptoms:
• Weight loss \> 10% within the previous 6 months
• Extreme fatigue attributed to CLL

You may not qualify if:

• 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/acquired immunodeficiency syndrome \[AIDS\])
• Infection with known chronic, active Hepatitis C
• Positive serology for hepatitis B (HB) defined as a positive test for HB surface antigen (HBsAg); in addition, if negative for HBsAg but HB core antibody (HBcAb) positive (regardless of HBsAb status), a HB deoxyribonucleic acid (DNA) test will be performed and if positive the subject will be excluded
• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (2)

• Strati P, Lanasa M, Call TG, Leis JF, Brander DM, LaPlant BR, Pettinger AM, Ding W, Parikh SA, Hanson CA, Chanan-Khan AA, Bowen DA, Conte M, Kay NE, Shanafelt TD. Ofatumumab monotherapy as a consolidation strategy in patients with previously untreated chronic lymphocytic leukaemia: a phase 2 trial. Lancet Haematol. 2016 Sep;3(9):e407-14. doi: 10.1016/S2352-3026(16)30064-3. Epub 2016 Aug 1.

  PMID: 27570087 DERIVED

• Baig NA, Taylor RP, Lindorfer MA, Church AK, LaPlant BR, Pettinger AM, Shanafelt TD, Nowakowski GS, Zent CS. Induced resistance to ofatumumab-mediated cell clearance mechanisms, including complement-dependent cytotoxicity, in chronic lymphocytic leukemia. J Immunol. 2014 Feb 15;192(4):1620-9. doi: 10.4049/jimmunol.1302954. Epub 2014 Jan 15.

  PMID: 24431228 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Cyclophosphamide; ofatumumab; Pentostatin

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Coformycin; Formycins; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Tait D. Shanafelt, M.D.
• Organization: Mayo Clinic

shanafelt.tait@mayo.edu

Study Officials

• Tait Shanafelt

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2009
• First Posted: December 2, 2009
• Study Start: March 1, 2010
• Primary Completion: May 1, 2013
• Study Completion: September 28, 2017
• Last Updated: September 18, 2018
• Results First Posted: September 18, 2018

Record last verified: 2017-09

Locations

US (4)