Lenalidomide and AT-101 in Treating Patients With Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Mayo Clinic
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01003769
First received: October 28, 2009
Last updated: October 1, 2014
Last verified: October 2014

October 28, 2009
October 1, 2014
September 2013
March 2015   (final data collection date for primary outcome measure)
  • Maximum tolerated dose of lenalidomide when given in combination with AT-101 [ Time Frame: Days 1-21 of course 2 ] [ Designated as safety issue: Yes ]
    Defined as the dose one level below the dose at which >= 2 of 3 patients or >= 2 of 6 patients experience dose-limiting toxicity during course 2.
  • Overall response rate (CR and PR) of including lenalidomide in combination with AT-101 [ Time Frame: At 6 and 12 months ] [ Designated as safety issue: No ]
  • Determine the maximum tolerated dose of lenalidomide in combination with AT-101 [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • Overall response rate including (CR & PR)of lenalidomide in combination with AT-101 at 6 month s and then 12 months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01003769 on ClinicalTrials.gov Archive Site
  • Frequency of subjects experiencing a specific adverse event [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Tabulated by body system, MedDRA term, and treatment cohort and summarized by worst NCI Common Toxicity Criteria (CTC) grade.
  • Time to progression for the combination of lenalidomide and AT-101 [ Time Frame: Until the time of disease progression, assessed up to 12 months ] [ Designated as safety issue: No ]
  • Effect of lenalidomide on the immune effector arm (T and NK cells) in peripheral blood [ Time Frame: Days 0, 1, 8, and 15 of course 1 and day 1 of course 2 ] [ Designated as safety issue: No ]
  • Changes in the immune cellular micro environment in bone marrow aspirate [ Time Frame: At baseline and day 1 of course 2 ] [ Designated as safety issue: No ]
  • Effect of specific molecular targets (including MCI-1, Akt, Erk1/2, Bcl-2, Bcl-xl, Puma, Noxa, and XIP) by Western blot analysis of peripheral blood [ Time Frame: At baseline, days 1, 8, and 15 of courses 1-2, and day 1 of course 3 ] [ Designated as safety issue: No ]
  • To evaluate the safety of the combination of lenalidomide and AT-101 in patients with relapsed or refractory B-CLL [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Time to progression (TTP)for the combination of Lenalidomide and AT-101 [ Time Frame: Until time of Disease progression ] [ Designated as safety issue: No ]
  • Conduct correlative studies for further understanding of the mechanism of antitumor activity of lenalidomide and AT-101 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Lenalidomide and AT-101 in Treating Patients With Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia
A Phase I/II Clinical Trial of Lenalidomide in Combination With AT-101 for the Treatment of Relapsed B-Cell Chronic Lymphocytic Leukemia (B-CLL)

This phase I/II trial studies the side effects and best dose of lenalidomide when given together with R-(-)-gossypol acetic acid and to see how well they work in treating patients with relapsed or refractory B-cell chronic lymphocytic leukemia (B-CLL). Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as R-(-)-gossypol acetic acid, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of lenalidomide in combination with AT-101 (R-(-)-gossypol acetic acid).

II. To evaluate overall response rate including (complete response [CR] + partial response [PR]) of lenalidomide in combination with AT-101 at 6 and then at 12 months.

SECONDARY OBJECTIVES:

I. To evaluate the safety of this combination in patients with relapsed or refractory B-CLL.

II. Time to progression (TTP) for the combination of lenalidomide + AT-101. III. To conduct correlative studies for further understanding of the mechanism of antitumor activity of lenalidomide and lenalidomide + AT-101.

OUTLINE: This is a phase I dose-escalation study of lenalidomide followed by a phase II study.

Patients receive lenalidomide orally (PO) once daily (QD) on days 1-21. Beginning in course 3, patients also receive AT-101 PO twice daily (BID) on days 1-3. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days and then every 3-4 months.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • B-cell Chronic Lymphocytic Leukemia
  • Refractory Chronic Lymphocytic Leukemia
  • Stage III Chronic Lymphocytic Leukemia
  • Stage IV Chronic Lymphocytic Leukemia
  • Drug: lenalidomide
    Given PO
    Other Names:
    • CC-5013
    • IMiD-1
    • Revlimid
  • Drug: R-(-)-gossypol acetic acid
    Given PO
    Other Name: AT-101
Experimental: Treatment (lenalidomide in combination with AT-101)
Patients receive lenalidomide PO QD on days 1-21. Beginning in course 2, patients also receive AT-101 PO BID on days 1-3. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Drug: lenalidomide
  • Drug: R-(-)-gossypol acetic acid
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
63
Not Provided
March 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Understand and voluntarily sign an informed consent form
  • Able to adhere to the study visit schedule and other protocol requirements
  • Diagnosis of B-CLL, confirmed by flow cytometric analysis and as per the criteria outlined by the International Workshop on Chronic Lymphocytic Leukemia (IWCLL)/Hallek December 2008
  • Any prior therapy for B-CLL must have been discontinued >= 28-days prior to registration
  • Patients must have absolute lymphocyte counts (ALC) of more than 5,000 cell/mm^3
  • During Phase I: All patients with relapsed disease will be eligible if they have received at least 1 prior standard CLL therapy and no more than 4 prior therapies (one of which must be a purine analog and/or an alkylating agent)
  • During Phase II: All patients with relapsed disease will be eligible if they have received a minimum of 1 prior standard therapy and a maximum of 2 prior treatments (one of which must be a purine analog and/or an alkylating agent) for B-CLL and have developed relapse disease

Note: Patients who have refractory disease (defined as - progressive disease on last treatment, or less than 6 months of clinical response to the last treatment) will not be eligible

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at registration
  • Absolute neutrophil count >= 1500/mm^3
  • Platelet count >= 30,000/mm^3
  • Serum creatinine =< 1.5 x upper limit of normal (ULN)
  • Total bilirubin =< 1.5 mg/dL or direct bilirubin =< 1.0mg/dL for patients with Gilberts syndrome
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2 x ULN or =< 5 x ULN if hepatic disease is present
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL 10-14 days prior to and again within 24 hours before starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
  • All study participants must be registered into the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist
  • Patient must require treatment for symptomatic B-CLL as defined by the by the IWCLL/Hallek, December 2008 criterion or as determined clinically necessary by the treating physician
  • Willing to provide blood and baseline bone marrow aspirate samples for correlative research purposes

Exclusion Criteria:

  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
  • Pregnant or lactating females
  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
  • Use of any other experimental drug or therapy =< 28 days prior to registration
  • Known hypersensitivity to thalidomide or lenalidomide
  • The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
  • Patients with of history of any other cancer (except nonmelanoma skin cancer or carcinoma in-situ of the cervix, unless in complete remission and off therapy for that disease for > 3 years)
  • Patient with history of cardiac arrest within the past 6 months
  • Patients with history of prior bowel resection, malabsorption syndrome, inflammatory bowel disease, prior bowel obstruction (partial or complete), Crohn disease, or any other disease significantly affecting the gastrointestinal tract
  • Prior use of gossypol or AT-101
Both
18 Years to 69 Years
No
United States
 
NCT01003769
MC128A, NCI-2009-01569, MC128A, P30CA015083
Yes
Mayo Clinic
Mayo Clinic
National Cancer Institute (NCI)
Principal Investigator: Asher Chanan-Khan Mayo Clinic
Mayo Clinic
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP