Ph2 Gem/Nov/Rituxan Rel/Ref MantleCell

• Sponsor: US Oncology Research (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00656084
• Collaborator: Eli Lilly and Company (Industry)
• Enrollment: 16
• Arm: 1
• Duration (Months): 37

Study Details

Study Description

Brief Summary

To determine the efficacy (response rate) produced by the combination of Gemzar, Novantrone, and Rituxan in relapsed or refractory MCL

Condition or Disease	Intervention/Treatment	Phase
Relapsed or Refractory Mantle Cell Lymphoma (MCL)	Drug: gemcitabine; Drug: mitoxantrone; Drug: rituximab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Gemzar, Novantrone and Rituxan in Relapsed or Refractory Mantle Cell Lymphoma (MCL) (B9E-US-X436)
• Study Start Date: Dec 1, 2004
• Actual Primary Completion Date: Jan 1, 2007
• Actual Study Completion Date: Jan 1, 2008

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Experimental arm Patients will be treated a maximum of 8 cycles or until the patient has evidence of a response, progressive disease, or until intolerable toxicity develops. Patients with a complete response will receive an additional 2 cycles of treatment (not to exceed 8 cycles). Drug order is gemcitabine, mitoxantrone, and rituximab.

Drug: gemcitabine; 900 mg/m2 on Days 1 and 8 of each 21-day cycle The order of administration will be: Gemzar-->Novantrone-->Rituxan.; Other Names: Gemzar ; Drug: mitoxantrone; Novantrone 10 mg/m2on Day 1. The order of administration will be: Gemzar-->Novantrone-->Rituxan.; Other Names: Novantrone ; Drug: rituximab; Rituxan 375 mg/m2 on Day 1. The order of administration will be: Gemzar-->Novantrone-->Rituxan.; Other Names: Rituxan

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (CR + PR) [2 years]

   Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD.

Secondary Outcome Measures

1. Duration of Response [From date of randomization until the date of first documented progression or the date of death from any cause, whichever came first, assessed up to 33 months.]

   The duration of response is measured from the time measurement criteria are first met for CR/PR until the first date that recurrent or progressive disease is objectively documented. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD.

2. Overall Survival (OS) Rate at 1 Year [1 year.]

   OS is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date.

3. Progression-free Survival Rate at 1 Year. [1 year.]

   PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Stage III or IV, histologically confirmed relapsed or refractory MCL as reviewed by the SI

• Is CD20 positive (by immunohistochemistry or FACS)

• Is Cyclin D positive (by immunohistochemistry or FACS)

• Has received prior chemotherapy (required minimum of 1 prior therapies)

• Has received prior treatment with Rituxan

• Has an ECOG Performance Status (PS) 0-2

• Is greater than or equal to 18 years of age

• Has appropriate laboratory values (please refer to protocol for specific laboratory values)

• If a history of cardiac disease is indicated, patient has an LVEF greater than or equal to 50% (MUGA)

• Has a negative serum pregnancy test within 7 days prior to registration (female patients of childbearing potential)

• If fertile, patient (male or female) has agreed to use an acceptable method of birth control to avoid pregnancy for the duration of the study and for a period of 2 months thereafter

• Has signed a Patient Informed Consent Form

• Has signed a Patient Authorization Form

Exclusion Criteria:

• Has other lymphomas not classified as MCL

• Has had prior treatment with Gemzar and/or Novantrone

• A history of known hypersensitivity to Gemzar, Novantrone, Rituxan, or any component of these drugs

• Has a history of hypersensitivity to murine-cell derived therapeutics

• Has a LVEF indicative of a cardiac condition (LVEF < 50%)

• Is receiving concurrent immunotherapy

• Has evidence of CNS involvement

• Has a serious uncontrolled intercurrent medical or psychiatric illness, including serious infection

• Has a history of other malignancy within the last 5 years (except cured basal cell carcinoma of skin and carcinoma insitu of uterine cervix), which could affect the diagnosis or assessment of any of the study drugs

• Is a pregnant or nursing woman

• Is unable to comply with requirements of study

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• US Oncology Research
• Eli Lilly and Company

Investigators

• Principal Investigator: Lawrence Garbo, MD, US Oncology Research

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00656084
• Other Study ID Numbers: 04-026
• First Posted: Apr 10, 2008
• Last Update Posted: Nov 3, 2016
• Last Verified: Sep 1, 2016

• Additional relevant MeSH terms: Lymphoma; Lymphoma, Mantle-Cell; Gemcitabine; Rituximab; Mitoxantrone

Study Results

Participant Flow

Arm/Group Title	Gemzar + Novantrone + Rituxan
Arm/Group Description	Gemzar, Novantrone, and Rituxan in relapsed or refractory mantle cell lymphoma (MCL)
Period Title: Overall Study
STARTED	16
COMPLETED	9
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	Gemzar + Novantrone + Rituxan
Arm/Group Description	Gemzar, Novantrone, and Rituxan in relapsed or refractory mantle cell lymphoma (MCL)
Overall Participants	16
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68 (12.3)
Sex: Female, Male (Count of Participants)
Female	5 31.3%
Male	11 68.8%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	16 100%
Region of Enrollment (participants) [Number]
United States	16 100%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (CR + PR)
Description	Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Evaluable Population

Arm/Group Title	Gemzar + Novantrone + Rituxan
Arm/Group Description	Gemzar, Novantrone, and Rituxan in relapsed or refractory mantle cell lymphoma (MCL)
Measure Participants	15
Number (95% Confidence Interval) [percentage of participants]	46.7 291.9%

2. Secondary Outcome

Title	Duration of Response
Description	The duration of response is measured from the time measurement criteria are first met for CR/PR until the first date that recurrent or progressive disease is objectively documented. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD.
Time Frame	From date of randomization until the date of first documented progression or the date of death from any cause, whichever came first, assessed up to 33 months.

Outcome Measure Data

Analysis Population Description

For patients who achieve a major objective response (CR or PR) the time to response will be assessed as the date of registration to the date of response.

Arm/Group Title	Gemzar + Novantrone + Rituxan
Arm/Group Description	Gemzar, Novantrone, and Rituxan in relapsed or refractory mantle cell lymphoma (MCL)
Measure Participants	7
Median (Full Range) [months]	7.9

3. Secondary Outcome

Title	Overall Survival (OS) Rate at 1 Year
Description	OS is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date.
Time Frame	1 year.

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Gemzar + Novantrone + Rituxan
Arm/Group Description	Gemzar, Novantrone, and Rituxan in relapsed or refractory mantle cell lymphoma (MCL)
Measure Participants	16
Number (95% Confidence Interval) [Probability of Survival]	0.57

4. Secondary Outcome

Title	Progression-free Survival Rate at 1 Year.
Description	PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date.
Time Frame	1 year.

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Gemzar + Novantrone + Rituxan
Arm/Group Description	Gemzar, Novantrone, and Rituxan in relapsed or refractory mantle cell lymphoma (MCL)
Measure Participants	16
Number (95% Confidence Interval) [Probability of Progression-free Survival]	0.54

Adverse Events

Time Frame	During the whole treatment period, up to 30 days following last dose.
Adverse Event Reporting Description	For treated patients only, assessed at each treatment visit.
Arm/Group Title	Gemzar + Novantrone + Rituxan
Arm/Group Description	Gemzar, Novantrone, and Rituxan in relapsed or refractory mantle cell lymphoma (MCL)
All Cause Mortality
	Gemzar + Novantrone + Rituxan
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Gemzar + Novantrone + Rituxan
	Affected / at Risk (%)	# Events
Total	4/15 (26.7%)
Gastrointestinal disorders
PAIN ABDO	1/15 (6.7%)	1
General disorders
CACHEXIA	1/15 (6.7%)	1
FEVER	2/15 (13.3%)	3
Other (Not Including Serious) Adverse Events
	Gemzar + Novantrone + Rituxan
	Affected / at Risk (%)	# Events
Total	15/15 (100%)
Blood and lymphatic system disorders
ANEMIA	13/15 (86.7%)	49
EDEMA PERIPH	1/15 (6.7%)	4
FEBRILE NEUTROPENIA	1/15 (6.7%)	1
LEUKOPENIA	9/15 (60%)	50
NEUTROPENIA	15/15 (100%)	64
THROMBOCYTHEM	1/15 (6.7%)	3
THROMBOCYTOPENIA	12/15 (80%)	63
Gastrointestinal disorders
ABDO ENLARGE	1/15 (6.7%)	1
ANOREXIA	7/15 (46.7%)	10
CONSTIP	6/15 (40%)	7
DEHYDRAT	1/15 (6.7%)	1
DIARRHEA	2/15 (13.3%)	3
DRY MOUTH	3/15 (20%)	3
FLATUL	1/15 (6.7%)	1
NAUSEA	9/15 (60%)	15
PAIN ABDO	2/15 (13.3%)	2
RECTAL DIS	1/15 (6.7%)	1
TASTE PERVERS	3/15 (20%)	3
VOMIT	2/15 (13.3%)	3
General disorders
ASTHENIA	14/15 (93.3%)	35
CHILLS	2/15 (13.3%)	4
DEPRESSION	1/15 (6.7%)	1
FEVER	3/15 (20%)	3
HEADACHE	1/15 (6.7%)	2
INSOMNIA	1/15 (6.7%)	1
PAIN	3/15 (20%)	3
SWEAT	2/15 (13.3%)	4
WEIGHT DEC	2/15 (13.3%)	2
Immune system disorders
ALLERG REACT	2/15 (13.3%)	3
Infections and infestations
CELLULITIS	1/15 (6.7%)	1
INFECT	2/15 (13.3%)	2
Investigations
PAIN CHEST SUBSTERN	1/15 (6.7%)	1
PALLOR	1/15 (6.7%)	2
PLAT ABNORM	1/15 (6.7%)	1
VASODILAT	1/15 (6.7%)	1
Metabolism and nutrition disorders
BILIRUBINEM	1/15 (6.7%)	1
BUN INC	1/15 (6.7%)	1
CREATININE INC	1/15 (6.7%)	1
HYPERGLYCEM	2/15 (13.3%)	4
HYPERURICEM	1/15 (6.7%)	1
HYPOCALCEM	2/15 (13.3%)	3
HYPONATREM	1/15 (6.7%)	1
HYPOPROTEINEM	2/15 (13.3%)	4
HYPOVOLEM	1/15 (6.7%)	1
LAB TEST ABNORM	1/15 (6.7%)	2
LDH INC	2/15 (13.3%)	2
PHOSPHATASE ALK INC	1/15 (6.7%)	1
Musculoskeletal and connective tissue disorders
ARTHRALGIA	1/15 (6.7%)	1
BACK PAIN	1/15 (6.7%)	1
MYALGIA	2/15 (13.3%)	2
PAIN BONE	1/15 (6.7%)	3
Nervous system disorders
DIZZINESS	3/15 (20%)	3
Renal and urinary disorders
HEMATURIA	1/15 (6.7%)	1
Respiratory, thoracic and mediastinal disorders
COUGH INC	1/15 (6.7%)	1
DYSPNEA	3/15 (20%)	5
FLU SYND	1/15 (6.7%)	1
RHINITIS	1/15 (6.7%)	1
STOMATITIS	1/15 (6.7%)	2
Skin and subcutaneous tissue disorders
ALOPECIA	3/15 (20%)	3
MUCOUS MEM DIS	1/15 (6.7%)	1
PRURITUS	2/15 (13.3%)	2
RASH	3/15 (20%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.