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

NCT01003769 | Terminated Phase 1 Results DMC

• 4 other identifiers: MC128ANCI-2009-01569P30CA0150833938
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

Brief Summary

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 B-cell chronic lymphocytic leukemia (B-CLL) that has returned after a period of improvement (relapsed). Biological therapies, such as lenalidomide, may stimulate the immune system to attack cancer cells. R-(-)-gossypol acetic acid may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and causing the cells to die. Giving lenalidomide with R-(-)-gossypol acetic acid may be an effective treatment for relapsed or refractory B-CLL. - Funding Source - FDA OOPD

Conditions

Recurrent Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose

  Maximum tolerated dose of lenalidomide when given in combination with AT-101, defined as the dose level below the lowest dose that induces dose limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) (Phase I)

  Up to day 28 of course 2

• Overall Response Rate (Complete Response [CR], CR With Incomplete Marrow Recovery, Clinical CR, Nodular Partial Response [PR], and PR) (Phase II)

  The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

  Up to 2 years

Secondary Outcomes (5)

• Incidence of Adverse Events, Graded According to the Grading Scale for Hematologic Adverse Events in CLL Studies (Phase I)

  Up to 2 years

• Incidence of Toxicity, Defined as Adverse Events Classified as Possibly, Probably, or Definitely Related to Study Treatment, Graded According to the Grading Scale for Hematologic Adverse Events in CLL Studies or Ordinal Common Toxicity Criteria (Phase I)

  Up to 2 years

• Overall Response Rate (Phase II)

  Up to 12 months

• Time to Progression (Phase II)

  The time from registration to the earliest date of documentation of disease progression, assessed up to 2 years

• Incidence of Adverse Events, Graded According to the Grading Scale for Hematologic Adverse Events in CLL Studies (Phase II)

  Up to 30 days after the last day of study treatment

Study Arms (1)

Treatment (lenalidomide in combination with AT-101)

EXPERIMENTAL

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 28 days for up to 11 courses (49-56 days for course 12 or last course of treatment) in the absence of disease progression or unacceptable toxicity.

Drug: Lenalidomide; Drug: R-(-)-Gossypol Acetic Acid; Other: Laboratory Biomarker Analysis

Interventions

Lenalidomide DRUG

Given PO

Also known as: CC-5013, CC5013, CDC 501, IMiD-1

Treatment (lenalidomide in combination with AT-101)

R-(-)-Gossypol Acetic Acid DRUG

Given PO

Also known as: (-)-Gossypol Acetic Acid, AT-101

Treatment (lenalidomide in combination with AT-101)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (lenalidomide in combination with AT-101)

Eligibility Criteria

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

You may qualify if:

• 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 =\< 1.0 mg/dL for patients with Gilberts syndrome
• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (2)

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Lenalidomide; gossypol acetic acid

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)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Asher Alban Chanan-Khan, M.D.
• Organization: Mayo Clinic

chanan-khan.asher@mayo.edu

(716) 845-3221

Study Officials

• Asher Chanan-Khan

  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: October 28, 2009
• First Posted: October 29, 2009
• Study Start: July 9, 2015
• Primary Completion: December 14, 2018
• Study Completion: December 14, 2018
• Last Updated: June 16, 2020
• Results First Posted: June 16, 2020

Record last verified: 2020-06

Locations

US (2)