CCI-779 and Rituximab in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
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| ClinicalTrials.gov Identifier: NCT00109967 |
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Recruitment Status :
Completed
First Posted : May 4, 2005
Results First Posted : January 22, 2014
Last Update Posted : April 17, 2014
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Recurrent Mantle Cell Lymphoma | Biological: rituximab Drug: temsirolimus | Phase 2 |
PRIMARY OBJECTIVES:
I. Determine the overall response rate in patients with relapsed or refractory mantle cell lymphoma treated with CCI-779 and rituximab.
II. Determine the tolerability of this regimen in these patients by assessing toxicity.
SECONDARY OBJECTIVES:
I. Determine the time to disease progression and overall survival of patients treated with this regimen.
II. Determine the duration of response in patients treated with this regimen.
OUTLINE: Patients are stratified according to prior response to rituximab (sensitive [partial response (PR) or complete response (CR) that lasted ≥ 6 months after the last treatment with rituximab alone or in combination with chemotherapy] vs refractory [stable or progressive disease OR a PR or CR that lasted < 6 months after the last treatment with rituximab alone or in combination with chemotherapy]).
Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 and on day 1 only of courses 3, 5, 7, 9, and 11. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of course 3, patients undergo reevaluation. Patients achieving a CR or an unconfirmed CR (CRu) receive 2 additional courses of treatment for a total of 5 courses. Patients achieving a PR or stable disease continue study treatment as outlined above for up to 12 courses. Patients achieving a PR or stable disease who subsequently achieve a CR or CRu between courses 3 and 10 receive 2 additional courses of treatment.
After completion of study treatment, patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually for 2 years.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 71 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase II Study of CCI-779 in Combination With Rituximab in Patients With Relapsed or Refractory Mantle Cell Lymphoma |
| Study Start Date : | May 2005 |
| Actual Primary Completion Date : | September 2009 |
| Actual Study Completion Date : | March 2012 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm I
Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 and on day 1 only of courses 3, 5, 7, 9, and 11. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of course 3, patients undergo reevaluation. Patients achieving a CR or an unconfirmed CR (CRu) receive 2 additional courses of treatment for a total of 5 courses. Patients achieving a PR or stable disease continue study treatment as outlined above for up to 12 courses. Patients achieving a PR or stable disease who subsequently achieve a CR or CRu between courses 3 and 10 receive 2 additional courses of treatment.
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Biological: rituximab
375 mg/m^2 Given IV
Other Names:
Drug: temsirolimus 25 mg given IV
Other Names:
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- Overall Response Rate (Complete and Partial Responses) as Defined by the International Workshop Criteria [ Time Frame: Up to 12, 28-day cycles. ]
Complete Response (CR) - Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms.
Partial Response (PR) requires a >=50% decrease in sum of the products of the greatest dimension (SPD) of the six largest dominant nodes or nodal masses.
Overall Response Rate (ORR) - The number of patients who achieve a CR or PR divided by the total number of evaluable patients.
We report the Overall Response Rate here.
- Time to Progression [ Time Frame: Patients were followed up to five years after registration. ]Time to progression was defined as the time from registration to the date of progression. Patients who died without disease progression were censored at the date of their last evaluation. Patients who were still receiving treatment at the time of these analyses were censored at the date of their last evaluation. The distribution of this time-to-event end point was estimated using the Kaplan-Meier method.
- Duration of Response [ Time Frame: Response duration is followed up to 5 years from registration. ]Duration of response was defined as the time from the date of documented response to the date of progression. Patients who went off treatment due to other reasons (eg, adverse reactions, refusal of further treatment) were censored at that time. The distribution of this time-to-event end point was estimated using the Kaplan-Meier method.
- Toxicity [ Time Frame: Assessed during treatment (up to 12, 28-day cycles) ]
As per the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) Version 3, toxicity was defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment by the treating physician.
In this section, we report the number of participants that experienced at least one Grade 3 or higher adverse event.
- Overall Survival [ Time Frame: Patients were followed for survival status for up to 5 years. ]Overall survival (OS) was defined as the time from registration to death resulting from any cause. The distribution of this time-to-event end point was estimated using the Kaplan-Meier method.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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Histologically confirmed* mantle cell lymphoma (MCL)
- Relapsed, refractory, or stable disease after prior treatment
- Tumor must be cyclin D-1 by immunohistochemistry OR 11;14 translocation by fluorescent in situ hybridization or cytogenetics
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Measurable disease, defined as ≥ 1 of the following:
- Unidimensionally measurable lymph node or tumor mass ≥ 2 cm by CT scan or MRI
- Splenic enlargement if spleen is palpable ≥ 3 cm below the left costal margin
- Malignant lymphocytosis if absolute lymphocytic count ≥ 5,000 AND lymphocytes confirmed to be monoclonal by flow cytometry
- No known central nervous system involvement (e.g., parenchymal mass or leptomeningeal involvement)
- Performance status - Eastern Cooperative Oncology Group (ECOG) 0-2
- At least 3 months
- No other concurrent treatment for MCL
- Absolute neutrophil count ≥ 1,000/mm^3
- Platelet count ≥ 75,000/mm^3
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- Direct bilirubin < 1.5 times ULN
- Aspartate aminotransferase (AST) ≤ 3 times ULN (5 times ULN if liver involvement by MCL is present)
- Creatinine ≤ 2 times ULN
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after completion of study treatment
- Cholesterol ≤ 350 mg/dL
- Fasting triglycerides < 400 mg/dL
- No known HIV positivity
- No ongoing or active infection
- No psychiatric illness or social situation that would preclude study compliance
- No other uncontrolled illness
- No other active malignancy requiring treatment OR that would preclude assessment of response to study drugs
- Prior biologic response modifiers allowed
- Prior immunotherapy allowed
- Prior high-dose therapy with stem cell support (i.e., stem cell transplantation) allowed
- No concurrent prophylactic growth factor to support neutrophils
- Prior chemotherapy allowed
- No other concurrent chemotherapy
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No concurrent corticosteroids to induce an antitumor response
- Concurrent corticosteroids (≤ 10 mg/day of prednisone or equivalent) for adrenal insufficiency or acute allergic reactions allowed
- Prior radiotherapy allowed
- No prior treatment with a mammalian target of rapamycin (mTOR) inhibitor
- No other concurrent investigational or commercial agents or therapies for MCL
- No other concurrent immunosuppressive therapy
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00109967
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| Principal Investigator: | Stephen Ansell | North Central Cancer Treatment Group |
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00109967 |
| Other Study ID Numbers: |
NCI-2009-00644 N038H U10CA025224 ( U.S. NIH Grant/Contract ) CDR0000425334 ( Registry Identifier: PDQ (Physician Data Query) ) |
| First Posted: | May 4, 2005 Key Record Dates |
| Results First Posted: | January 22, 2014 |
| Last Update Posted: | April 17, 2014 |
| Last Verified: | December 2013 |
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Lymphoma Lymphoma, Mantle-Cell Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Lymphoma, Non-Hodgkin Sirolimus Rituximab |
Antineoplastic Agents, Immunological Antineoplastic Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Anti-Bacterial Agents Anti-Infective Agents Antibiotics, Antineoplastic Antifungal Agents Immunosuppressive Agents |