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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00117598
First received: June 30, 2005
Last updated: February 2, 2012
Last verified: February 2012
  Purpose

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


Condition Intervention Phase
Lymphoma
Drug: Temsirolimus (CCI-779)
Drug: Investigator's choice
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    The period from randomization until disease progression, death or date of last contact.


Secondary Outcome Measures:
  • Percentage of Participants With Objective Response [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.


Enrollment: 169
Study Start Date: May 2005
Study Completion Date: January 2011
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: Temsirolimus (CCI-779)
Temsirolimus 175 mg IV once a week for 3 weeks; followed by 75 mg IV once a week
Experimental: B Drug: Temsirolimus (CCI-779)
Temsirolimus 175 mg IV once a week for 3 weeks; followed by 25 mg IV once a week
Active Comparator: C Drug: Investigator's choice

Any of the following single agent treatments:

  1. Fludarabine 25 mg/m2 IV over 30 minutes daily for 5 consecutive days, every 28 days or oral administration, as appropriate.
  2. 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
  3. 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
  4. 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
  5. Cladribine 5 mg/m2 IV daily for 5 consecutive days, every 28 days for 2-6 cycles depending on response,
  6. 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
  7. Prednisone 40 (20-60) mg/m2 PO daily or every other day
  8. Dexamethasone 20(20-40) mg PO/IV daily for 5 consecutive days, every 14 - 28 day

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00117598

  Show 72 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00117598     History of Changes
Obsolete Identifiers: NCT00326547
Other Study ID Numbers: 3066K1-305
Study First Received: June 30, 2005
Results First Received: February 2, 2012
Last Updated: February 2, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Sirolimus
Everolimus
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on April 23, 2014