Study Evaluating Temsirolimus (CCI-779) In Mantle Cell Lymphoma (MCL)

Study Overview
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Brief Summary
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This is an open-label, randomized trial in relapsed refractory subjects with mantle cell lymphoma (MCL).

Official Title
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An Open-Label, Randomized, Phase 3 Trial Of Intravenous Temsirolimus (CCI-779) At Two Dose Levels Compared To Investigator's Choice Therapy In Relapsed, Refractory Subjects With Mantle Cell Lymphoma (MCL)

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: Temsirolimus (CCI-779)
* Drug: Temsirolimus (CCI-779)
* Drug: Investigator's choice


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Mantle cell lymphoma (MCL) confirmed with histology, immunophenotype, and cyclin D1 analysis Received 2 to 7 prior therapies which may include hematopoietic stem cell transplant (i.e. induction + consolidation + maintenance) Prior treatment with an alkylating agent and an anthracycline, rituximab, individually or in combination, and status that is at least one of the following: Primary disease refractory to at least 2 regimens; Refractory to at least 1 regimen after first relapse; Refractory or untreated after second or greater relapse; Refractory to first line and relapsed after second line. Chemotherapy combinations may include, but are not limited to: CHOP (Cyclophosphamide, doxorubicin, vincristine, prednisone), R-CHOP (Rituximab, Cyclophosphamide, doxorubicin, vincristine, prednisone), FCM (Fludarabine, cyclophosphamide, mitoxantrone), R-FCM (Rituximab,Fludarabine, cyclophosphamide, mitoxantrone), ICE(Ifosfamide, carboplatin, etoposide), DHAP (Dexamethasone, cisplatin, cytarabine) and hyper-CVAD (Cyclophosphamide, doxorubicin, vincristine, dexamethasone). Exclusion Criteria: Subjects who are less than or equal to six month from allogeneic hematopoietic stem cell transplant and who are on immunosuppressive therapy or have evidence of graft versus host disease Prior investigational therapy within 3 weeks of first dose. Investigational therapy is defined as treatment that is not approved for any indication. Active central nervous system (CNS) metastases, as indicated by clinical symptoms, cerebral edema, requirement for corticosteroids and/or progressive growth. (Treated CNS metastases must be stable for > 2 weeks prior to Day 1.)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: Temsirolimus (CCI-779)<br>* Temsirolimus 175 mg IV once a week for 3 weeks; followed by 75 mg IV once a week<br>|
| Experimental: B<br> | Drug: Temsirolimus (CCI-779)<br>* Temsirolimus 175 mg IV once a week for 3 weeks; followed by 25 mg IV once a week<br>|
| Active Comparator: C<br> | Drug: Investigator's choice<br>* Any of the following single agent treatments: Fludarabine 25 mg/m2 IV over 30 minutes daily for 5 consecutive days, every 28 days or oral administration, as appropriate. Chlorambucil 0.1 (0.1-0.2) mg/kg PO daily for 3 to 6 weeks as required OR 0.4 (0.3 0.8) mg/kg PO every 21 to 28 days Gemcitabine 1 gm/m2 IV over 30 minutes on days 1, 8 and 15 every 28 days or day 1 and day 8 every 21 days Cyclophosphamide 300 (200-450) mg/m2 PO daily for 5 consecutive days every 21 to 28 days, OR 600 (400-1200) mg/m2 IV every 21 to 28 days Cladribine 5 mg/m2 IV daily for 5 consecutive days, every 28 days for 2-6 cycles depending on response, Etoposide 50 (50-150) mg/m2 IV daily for 3-5 days every 21 to 28 days OR 100 (50 300) mg/m2 PO daily for 3-5 days every 21 to 28 days Prednisone 40 (20-60) mg/m2 PO daily or every other day Dexamethasone 20(20-40) mg PO/IV daily for 5 consecutive days, every 14 - 28 day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | The period from randomization until disease progression, death or date of last contact. | Baseline, every 8 weeks up to Year 1, then every 12 weeks up to Year 2, and then every 6 months until tumor progression or death (up to Year 5) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Objective Response | Assessment of complete or partial response (CR, PR) or uncomplete response (CRu) using Response Evaluation Criteria in Solid Tumors. CR: 1) No disease evident. 2) Lymph node, nodal mass regressed to normal size. 3) Previously enlarged organ ↓ size. 4) Bone marrow clear on repeat aspirate, biopsy. CRu: CR 1 and 3, at least 1 of following: Lymph node regressed >75%. Bone marrow ↑ number or aggregate size, no cytologic/architectural atypia. PR: ≥50% ↓ index lesion, no size ↑ in other nodes, liver, spleen. Splenic and hepatic nodule regressed ≥50%. No new disease. | Baseline, every 8 weeks up to Year 1, then every 12 weeks up to Year 2, and then every 6 months until tumor progression or death (up to Year 5) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphoma