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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 14, 2014