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
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
First received: October 28, 2009
Last updated: October 1, 2014
Last verified: October 2014

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.

Condition Intervention Phase
B-cell Chronic Lymphocytic Leukemia
Refractory Chronic Lymphocytic Leukemia
Stage III Chronic Lymphocytic Leukemia
Stage IV Chronic Lymphocytic Leukemia
Drug: lenalidomide
Drug: R-(-)-gossypol acetic acid
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:

Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 63
Study Start Date: September 2013
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: lenalidomide
Given PO
Other Names:
  • CC-5013
  • IMiD-1
  • Revlimid
Drug: R-(-)-gossypol acetic acid
Given PO
Other Name: AT-101

Detailed Description:


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.


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.


Ages Eligible for Study:   18 Years to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  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: NCT01003769

United States, Florida
Mayo Clinic in Florida Recruiting
Jacksonville, Florida, United States, 10029
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Asher Chanan-Khan, M.D.         
United States, New York
Roswell Park Cancer Institute Terminated
Buffalo, New York, United States, 14263
Sponsors and Collaborators
Mayo Clinic
Principal Investigator: Asher Chanan-Khan Mayo Clinic
  More Information

No publications provided

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT01003769     History of Changes
Obsolete Identifiers: NCT01021345
Other Study ID Numbers: MC128A, NCI-2009-01569, MC128A, P30CA015083
Study First Received: October 28, 2009
Last Updated: October 1, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Gossypol acetic acid
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Antispermatogenic Agents
Contraceptive Agents
Contraceptive Agents, Female
Contraceptive Agents, Male
Growth Inhibitors
Growth Substances
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Spermatocidal Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on March 26, 2015