Everolimus and Alemtuzumab in Treating Patients With Recurrent Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

NCT00935792 | Completed Phase 1 Results DMC

• 3 other identifiers: MC088CNCI-2009-0093508-008775
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Everolimus may stop the growth of cancer cells by blocking some of the signaling molecules needed for cell growth. Monoclonal antibodies, such as alemtuzumab, can bind to and kill malignant lymphocytes. PURPOSE: This phase I/II trial is studying the side effects and best dose of everolimus when given together with alemtuzumab and will see how well they work in treating patients with recurrent chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL).

Conditions

Lymphocytic Leukemia

Keywords

hematopoietic cancer; lymphoid cancer

Outcome Measures

Primary Outcomes (3)

• Clinical Response (Complete or Partial Remission)

  CR requires all of the following for a period of at least 2months:Absence of lymphadenopathy.No hepatomegaly or splenomegaly.Absence of constitutional symptoms.• Neutrophils\>1500/ul•Platelets\>100,000/ul • Hemoglobin \>11.0gm/dl• Peripheral blood lymphocytes \<4000/uLBonemarrow. normocellular with\<30%of nucleated cells being lymphocytes.PR requires two for 2+months.≥50%decrease in peripheral blood lymphocyte count from the pretreatment baseline value.≥ 50%reduction in the sum of the products of the maximal perpendicular diameters of the largest measured node or nodal masses in the right and left cervical, axillary, and inguinal lymph node regions.≥ 50%reduction in size of liver and/or spleen noting the maximal distance below the respective costal margins of palpable hepatosplenomegaly during rest.Neutrophils\>1500/ul or50%improvement over baseline. Platelets\>100,000/ul or50%increase over baseline. Hemoglobin\>11.0 gm/dl or50%increase over baseline without transfusions

  After 2 courses of treatment

• Number of Participants With Dose-Limiting Toxicities

  The maximum tolerated dose is the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients. A total of 6 patients treated at the MTD will be sufficient to identify common toxicities at the MTD. Dose-limiting toxicity will be defined as an adverse event attributed (definitely, probably, or possibly) to the study treatment and meeting the following criteria. Hematologic: ANC ≤ 0.3 x 109/L or platelet count \< 10 x 109/L Other nonhematologic: ≥grade 3 as per NCI Common Terminology Criteria for Adverse Events v3.0 except for fatigue, hyperlipidemia, and hyperglycemia.

  1 Month

• Test the Safety and Tolerability of the Combination of Everolimus and Alemtuzumab.

  The number and severity of all adverse events will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion. This will provide an indication of the level of tolerance for this treatment combination in this patient group. Below is the number of patients that experienced a grade 3+ Adverse event that was at least possibly related to Treatment.

  Up to 12 months past final treatment

Secondary Outcomes (4)

• Survival Time

  up to 5 years

• Progression-free Survival

  up to 5 years

• Duration of Response

  up to 5 years

• Time to Subsequent Therapy

  up to 5 years

Study Arms (1)

Arm I

EXPERIMENTAL

Patients receive oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.

Drug: alemtuzumab; Drug: everolimus

Interventions

alemtuzumab DRUG

Given subcutaneously

Also known as: anti-CD52 monoclonal antibody, MoAb CD52, Monoclonal Antibody Campath-1H, Campath-1H, Monoclonal Antibody CD52, Campath

Arm I

everolimus DRUG

Given orally

Also known as: Certican, RAD001, 42-O-(2-Hydroxy)ethyl Rapamycin

Arm I

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• CLL will be diagnosed if these cells have \>= 3 of the following characteristics: CD5+, CD23+, dim surface light chain expression, dim surface CD20 expression, AND FISH analysis is negative for IGH/CCND1 and/or immunostaining is negative for cyclin D1 expression to exclude mantle cell lymphoma Previous treatment for CLL Progressive disease: symptomatic CLL (weight loss\>10% within 6 months, extreme fatigue, fevers\>38.5 C, drenching night sweats without evidence of infection) OR evidence of progressive bone marrow failure (hemoglobin\<11g/dL, platelet count\<100 x 10\^9/L) OR massive (\>6 cm below left costal margin) or progressive palpable splenomegaly OR massive (\>10 cm) or measurable and progressive lymphadenopathy
• Please contact study investigator and/or consult protocol document for specific details on laboratory criteria CD52 expression by CLL cells Willing to provide mandatory biospecimen samples for research studies as required by the protocol Negative serum pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only Willingness to return to the enrolling institution for follow-up
• ECOG Performance Status (PS) 0, 1, or 2--Exceptions: Grade 3 allowed if caused by CLL and not other co-morbidities Provide informed written consent Life expectancy \>= 3 months

You may not qualify if:

• Any of the following comorbid conditions: NYHA class III-IV heart disease, recent myocardial infarction (\< 6 months prior to registration), uncontrolled infection, infection with the human immunodeficiency virus (HIV/AIDS), serological evidence of active hepatitis B infection (HBsAg or HBeAg positive) or positive hepatitis C serology, as further severe immunosuppression with this regimen may occur
• Evidence of active autoimmune hemolytic anemia, immune thrombocytopenia, or pure red blood cell aplasia Other active primary malignancy requiring treatment or that limits survival to =\< 2 years Any major surgery =\< 4 weeks prior to registration Concurrent investigational drug therapy Any of the following: pregnant women,nursing women, men or women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device \[IUD\], surgical sterilization, abstinence, etc.)
• Concomitant use of the following CYP3A4 strong inhibitors: Clarithromycin, Nefazodone, Telithromycin, Aprepitant, Indinavir, Nelfinavir, Diltiazem, Borisonazole, Itrazonazole, Ritonavir, Erythromycin, Ketoconazole, Saquinavir, Fluconazole (may be used if drug levels can be monitored)
• Patients with any known bleeding diathesis (any congenital bleeding disorder that affects platelet function and/or coagulation including von Willebrand's Disease)
• Severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air Receiving anticoagulant therapy

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (2)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphoid; Hematologic Neoplasms

Interventions

Alemtuzumab; Everolimus

Condition Hierarchy (Ancestors)

Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Timothy Call, M.D.
• Organization: Mayo Clinic

Call.Timothy@mayo.edu

5076682050

Study Officials

• Clive S. Zent, M.D.

  Mayo Clinic

  STUDY CHAIR

• Jose F. Leis, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2009
• First Posted: July 9, 2009
• Study Start: July 1, 2009
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: September 26, 2017
• Results First Posted: December 12, 2016

Record last verified: 2016-01

Locations

US (2)