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AIDS-Related Hodgkin LymphomaPhase 1/2NCT01076543

Lenalidomide and Temsirolimus in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma

A Phase 1/2 study testing Laboratory Biomarker Analysis, Lenalidomide and Temsirolimus in people with AIDS-Related Hodgkin Lymphoma and Recurrent Adult Hodgkin Lymphoma, run by National Cancer Institute (NCI) at 11 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase I/II trial studies the side effects and the best dose of lenalidomide when given together with temsirolimus and to see how well it works in treating patients with Hodgkin lymphoma or non-Hodgkin lymphoma that has come back after a period of improvement or is not responding to treatment. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Laboratory Biomarker Analysis, Lenalidomide and Temsirolimus
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
110 participants
Where
11 sitesUnited States
Study dates
15 Apr 2010to 30 Sep 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

  • Histology: bone marrow biopsies (with the exception of lymphoplasmacytic lymphoma) as the sole means of diagnosis are not acceptable; fine needle aspirates are not acceptable
  • Phase I: previously treated, histologically confirmed Hodgkin and non-Hodgkin lymphomas; the only exception to a requirement for a lymph node biopsy is lymphoplasmacytic lymphoma, which can be diagnosed based on morphologic evidence in the bone marrow plus the appropriate paraprotein
  • Phase II: previously treated, histologically confirmed mature non-Hodgkin lymphoma (NHL) stratified by histology:
  • Group A: diffuse large B-cell lymphoma (NOTE: all patients with DLBCL must have germinal center vs. non-germinal center phenotype established via immunohistochemistry)
  • Group B: follicular lymphoma
  • Group C: lymphoma NOS (including Hodgkin lymphoma, T-NHL, marginal zone lymphoma, lymphoplasmacytic
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  • No limit to number of prior therapies; prior autologous transplantation is allowed
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Absolute neutrophil count (ANC) >= 1,000/uL
  • Platelet count >= 75,000/uL
  • Total bilirubin =< 1.5 times upper limit of normal (ULN) (unless due to Gilbert's)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 times ULN
  • Creatinine clearance >= 60 mL/min as determined by calculated Cockcroft-Gault equation
  • Fasting serum cholesterol =< 350 mg/dL
  • Fasting serum triglycerides =< 2.5 times ULN
  • All patients are required to have measurable disease; non-measurable disease alone is not acceptable; any tumor mass > 1 cm is acceptable; lesions that are considered non-measurable include the following:
  • Bone lesions (lesions if present should be noted)
  • Ascites
  • Pleural/pericardial effusion
  • Lymphangitis cutis/pulmonis
  • Bone marrow (involvement by lymphoma should be noted)
  • For Waldenstrom's macroglobulinemia, measurable disease is defined as at least one lesion with a single diameter of greater than 2 cm by computed tomography or bone marrow involvement with greater than 10% malignant cells and quantitative monoclonal protein (immunoglobulin M [IgM], IgG, IgA) greater than 1,000 mg/dL
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days and again within 24 hours prior to starting cycle 1 of lenalidomide; further, they 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 starting 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; a FCBP 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 patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
  • Ability to understand and the willingness to sign a written informed consent document
  • Patients who are human immunodeficiency virus (HIV) positive are allowed to participate BUT must meet the following criteria:
  • No acquired immune deficiency syndrome (AIDS)-defining illness, AND
  • Cluster of differentiation (CD) 4 count >= 400 cells/mm^3, AND
  • No anti-retroviral therapy (including high-active antiretroviral therapy [HAART]) within 7 days of starting protocol therapy, AND
  • Patient may not take concurrent anti-retroviral therapy (including HAART) while on protocol
  • NOTE: it is not generally recommended to suspend anti-retroviral therapy (including HAART); the medical team enrolling a patient who suspends anti-retroviral therapy for the purpose of study participation must have a documented note reviewing the potential risks/benefits with the patient in the medical chart

Who cannot join

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients who are receiving any other investigational agents
  • Patients with known brain metastases should be excluded from this clinical trial
  • History of allergic reactions attributed to compounds of similar chemical or biological composition to temsirolimus or lenalidomide used in study
  • Patients requiring active anti-retroviral therapy for HIV are excluded
  • No "currently active" second malignancy, other than non-melanoma skin cancers; patients are not considered to have a "currently active" second malignancy if they have completed anti-cancer therapy and are considered by their physicians to be at less than 30% risk of relapse
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  • No history (within 3 months of study entry) of deep venous thrombosis/pulmonary embolism (DVT/PE); patients with a distant history (greater than 3 months before study entry) of DVT/PE are eligible, but should receive prophylactic aspirin or low molecular weight heparin
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients with relapsed/refractory DLBCL or HL who are eligible and willing to undergo potentially curative stem cell transplant
  • Patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) are excluded
  • No corticosteroids within 14 days prior to study, except for maintenance therapy for a non-malignant disease; maintenance therapy dose may not exceed 10 mg/day prednisone or equivalent; any patient on steroid therapy must receive thromboembolic prophylaxis

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • Fort Wayne Medical Oncology and Hematology Inc-Parkview

    Fort Wayne, Indiana, 46845

  • Ingalls Memorial Hospital

    Harvey, Illinois, 60426

  • Indiana University/Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • Illinois CancerCare-Peoria

    Peoria, Illinois, 61615

  • Central Illinois Hematology Oncology Center

    Springfield, Illinois, 62702

  • Southern Illinois University School of Medicine

    Springfield, Illinois, 62702

  • Mercy Hospital Saint Louis

    St Louis, Missouri, 63141

Other trials in United States

About this study

Official title: Phase I/II Investigation of Temsirolimus Plus Lenalidomide in Relapsed Non-Hodgkin Lymphomas

This phase I/II trial studies the side effects and the best dose of lenalidomide when given together with temsirolimus and to see how well it works in treating patients with Hodgkin lymphoma or non-Hodgkin lymphoma that has come back after a period of improvement or is not responding to treatment. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Lenalidomide may also stop the growth of Hodgkin lymphoma or non-Hodgkin lymphoma by blocking blood flow to the cancer. Temsirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving lenalidomide together with temsirolimus may kill more cancer cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the safety, toxicity, and maximum tolerated dose of lenalidomide when combined with temsirolimus in patients with relapsed lymphomas. (Phase I) II. To determine complete and overall response rate of lenalidomide plus temsirolimus in patients with relapsed lymphomas as stratified by histology: follicular lymphoma, diffuse large B-cell lymphoma, and lymphoma not otherwise specified (NOS) (including Hodgkin lymphoma, T-cell non-Hodgkin lymphoma [T-NHL], lymphoplasmacytic lymphoma, and mantle cell lymphoma). (Phase II) III. To determine duration of response, progression-free survival, and overall survival of lenalidomide plus temsirolimus in patients with relapsed lymphomas as stratified by histology: diffuse large B-cell lymphoma, follicular lymphoma, and lymphoma NOS (including Hodgkin lymphoma, T-NHL, lymphoplasmacytic lymphoma, mantle cell lymphoma). (Phase II)

SECONDARY OBJECTIVES:

  1. To determine mammalian target of rapamycin (mTOR) pathway activation in pre-treatment tumor tissue.

II. To determine angiogenic and microenvironmental status of pre-treatment tissue and peripheral blood samples, and to evaluate changes following treatment with temsirolimus and lenalidomide.

III. To determine differentially expressed genes associated with differences in clinical response and in progression-free survival (PFS) in patients with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) (Groups A and B, respectively).

IV. To determine a methylation signature predictive of clinical response and PFS in patients with DLBCL and FL (Groups A and B, respectively).

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

Patients receive lenalidomide orally (PO) on days 1-21 and temsirolimus intravenously (IV) over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease after 2 courses may continue therapy for up to 52 weeks.

After completion of study treatment, patients are followed up for 1 year.

Being tested
Laboratory Biomarker Analysis, Lenalidomide, Temsirolimus
Medical subject headings
Hodgkin Disease, Lymphoma, Follicular, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Non-Hodgkin, Lymphoma, T-Cell, Waldenstrom Macroglobulinemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • LenalidomideDrug

    Also called CC-5013, CC5013, CDC 501, Revlimid

    Given PO

  • TemsirolimusDrug

    Also called CCI-779, CCI-779 Rapamycin Analog, Cell Cycle Inhibitor 779, Rapamycin Analog

    Given IV

Study groups in NCT01076543
Study groupRoleWhat they receive
Treatment (lenalidomide, temsirolimus)ExperimentalPatients receive lenalidomide PO on days 1-21 and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease after 2 courses may continue therapy for up to 52 weeks.
Receives: Other: Laboratory Biomarker Analysis; Drug: Lenalidomide; Drug: Temsirolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Dose-limiting Toxicity (DLT), Phase I Patients Only

    Incidence of dose-limiting toxicity (DLT) defined as any grade 3 or 4 adverse events as graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)

    Measured: 28 days

  2. Complete Response (Phase II)

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions;

    Measured: Up to 1 year

  3. Overall Response Rate (Phase II)

    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: Up to 1 year

Secondary outcomes (2)

  1. Progression-free Survival (PFS) (Phase II)

    Kaplan-Meier curves will be generated for PFS stratified by histology; median PFS times will be determined and 90% confidence intervals derived as described in Brookmeyer and Crowley.

    Measured: Time from study entry until disease progression or death from any cause, assessed up to 5 years

  2. Overall Survival (OS) (Phase II)

    Kaplan-Meier curves will be generated for OS stratified by histology; median OS times will be determined and 90% confidence intervals derived as described in Brookmeyer and Crowley.

    Measured: Time from study entry until death from any cause, assessed up to 6 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Feb 2010 (estimated)
  2. Study start15 Apr 2010
  3. Primary completion31 Dec 2017
  4. Study completion30 Sep 2018

Resources

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
110 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01076543
Sponsor's protocol ID
NCI-2011-01456
Other IDs
NCI-2011-01456, 09-443-A, CDR0000666432, 8309, 8309, N01CM00071, N01CM62201, P30CA014599
Status last verified
Sep 2019
First submitted
25 Feb 2010
Last updated
16 Oct 2019
Data monitoring committee
No

Publications

  • Major A, Kline J, Karrison TG, Fishkin PAS, Kimball AS, Petrich AM, Nattam S, Rao K, Sleckman BG, Cohen K, Besien KV, Rapoport AP, Smith SM. Phase I/II clinical trial of temsirolimus and lenalidomide in patients with relapsed and refractory lymphomas. Haematologica. 2022 Jul 1;107(7):1608-1618. doi: 10.3324/haematol.2021.278853.

    PubMed 34320785

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Laboratory Biomarker Analysis, Lenalidomide and Temsirolimus in people with AIDS-Related Hodgkin Lymphoma and Recurrent Adult Hodgkin Lymphoma, run by National Cancer Institute (NCI) at 11 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 30 inclusion and 11 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: finished, as of the sponsor's last update on 16 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 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 Oct 2019). 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?

Incidence of Dose-limiting Toxicity (DLT), Phase I Patients Only (time frame: 28 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01076543, which also lists 1 linked publication.

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 Oct 2019.

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