Recurrent Chronic Lymphocytic LeukemiaPhase 1/2NCT01003769
Lenalidomide and AT-101 in Treating Patients With Relapsed B-Cell Chronic Lymphocytic Leukemia
A Phase 1/2 study testing Lenalidomide, R-(-)-Gossypol Acetic Acid and Laboratory Biomarker Analysis in people with Recurrent Chronic Lymphocytic Leukemia, run by Mayo Clinic at 2 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Chronic Lymphocytic Leukemia
- What is being tested?
- Lenalidomide, R-(-)-Gossypol Acetic Acid and Laboratory Biomarker Analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 2 sitesUnited States
- Study dates
- 9 Jul 2015to 14 Dec 2018
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
- A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Roswell Park Cancer Institute
Buffalo, New York, 14263
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980
About this study
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)
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
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) of lenalidomide in combination with AT-101 (R-(-)-gossypol acetic acid). (Phase I) II. To assess the overall response rate of lenalidomide in combination with AT-101. (Phase II)
SECONDARY OBJECTIVES:
- To assess the overall response rates of lenalidomide in combination with AT-101 at 6 months and 12 months.
II. To evaluate time to progression (TTP) for the combination of lenalidomide + AT-101.
III. To evaluate the safety of this combination in patients with relapsed B-CLL.
TERTIARY OBJECTIVES:
- 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 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.
After completion of study treatment, patients are followed up for 30 days and then every 3 months for up to 2 years.
- Conditions
- Recurrent Chronic Lymphocytic Leukemia
- Being tested
- Lenalidomide, R-(-)-Gossypol Acetic Acid, Laboratory Biomarker Analysis
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenalidomideDrug
Also called CC-5013, CC5013, CDC 501, IMiD-1
Given PO
R-(-)-Gossypol Acetic AcidDrug
Also called (-)-Gossypol Acetic Acid, AT-101
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Lenalidomide; Drug: R-(-)-Gossypol Acetic Acid; Other: Laboratory Biomarker Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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.
Measured: 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)
The number and severity of all adverse events (overall and by dose-level) will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion.
Measured: 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)
Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses. Here, we report the number of patients that reported a grade 2 or higher as their worst incidence of toxicity.
Measured: Up to 2 years
Overall Response Rate (Phase II)
The proportion of responses by 6 months will be estimated by the number of patients who achieve a response by 6 months divided by the total number of evaluable patients. The proportion of responses by 12 months will be estimated in a similar manner. Exact binomial 95% confidence intervals for the true success proportions will be calculated.
Measured: Up to 12 months
Time to Progression (Phase II)
The distribution of time to progression will be estimated using the method of Kaplan-Meier.
Measured: 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)
The maximum grade for each type of adverse event, regardless of causality, will be recorded and reported for each patient, and frequency tables will be reviewed to determine adverse event patterns.
Measured: Up to 30 days after the last day of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2009 (estimated)
- Study start9 Jul 2015
- Primary completion14 Dec 2018
- Study completion14 Dec 2018
Why it stopped: Lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Recurrent Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Asher Chanan-Khan, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01003769
- Sponsor's protocol ID
- MC128A
- Other IDs
- NCI-2009-01569, MC128A, P30CA015083, 3938
- Status last verified
- Jun 2020
- First submitted
- 28 Oct 2009
- Last updated
- 16 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01003769
- Acronym / sponsor ID
- MC128A
- Conditions
- Recurrent Chronic Lymphocytic Leukemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of funding
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 9 Jul 2015 (actual)
- Primary completion
- 14 Dec 2018 (actual)
- Study completion
- 14 Dec 2018 (actual)
- First posted
- 29 Oct 2009 (estimated)
- Results
- Posted 16 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) of lenalidomide in combination with AT-101 (R-(-)-gossypol acetic acid). (Phase I) II. To assess the overall response rate of lenalidomide in combination with AT-101. (Phase II)
SECONDARY OBJECTIVES:
- To assess the overall response rates of lenalidomide in combination with AT-101 at 6 months and 12 months.
II. To evaluate time to progression (TTP) for the combination of lenalidomide + AT-101.
III. To evaluate the safety of this combination in patients with relapsed B-CLL.
TERTIARY OBJECTIVES:
- 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 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.
After completion of study treatment, patients are followed up for 30 days and then every 3 months for up to 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (lenalidomide in combination with AT-101) | Experimental | Drug: Lenalidomide, Drug: R-(-)-Gossypol Acetic Acid, Other: Laboratory Biomarker AnalysisPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LenalidomideAlso: CC-5013, CC5013, CDC 501, IMiD-1Given PO | Drug | Treatment (lenalidomide in combination with AT-101) |
| R-(-)-Gossypol Acetic AcidAlso: (-)-Gossypol Acetic Acid, AT-101Given PO | Drug | Treatment (lenalidomide in combination with AT-101) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (lenalidomide in combination with AT-101) |
Primary outcome
Maximum Tolerated Dose
Time frame: Up to day 28 of course 2
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)
Overall Response Rate (Complete Response [CR], CR With Incomplete Marrow Recovery, Clinical CR, Nodular Partial Response [PR], and PR) (Phase II)
Time frame: Up to 2 years
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.
5 secondary outcomes
Incidence of Adverse Events, Graded According to the Grading Scale for Hematologic Adverse Events in CLL Studies (Phase I)
Time frame: 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)
Time frame: Up to 2 years
Overall Response Rate (Phase II)
Time frame: Up to 12 months
Time to Progression (Phase II)
Time frame: 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)
Time frame: Up to 30 days after the last day of study treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Asher Chanan-Khan principal investigator
Mayo Clinic
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Lenalidomide, R-(-)-Gossypol Acetic Acid and Laboratory Biomarker Analysis in people with Recurrent Chronic Lymphocytic Leukemia, run by Mayo Clinic at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (time frame: Up to day 28 of course 2). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2020.