NCT00875667: Sprint

A Study to Determine the Efficacy of Lenalidomide Versus Investigator's Choice in Patients With Relapsed or Refractory Mantle Cell Lymphoma (MCL)

Completed Phase 2 Results posted Last updated 16 September 2019

What this trial tests

Phase 2 trial testing Lenalidomide in Mantle Cell Lymphoma in 254 participants. Completed in 9 October 2018.

Timeline

30 April 2009

Primary endpoint
28 June 2018

9 October 2018

Quick facts

Lead sponsor	Celgene
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	254
Start date	30 April 2009
Primary completion	28 June 2018
Estimated completion	9 October 2018
Sites	97 locations across Denmark, France, Italy, Netherlands, Greece, Russia, Belgium, Sweden

Drugs / interventions tested

• Lenalidomide — full drug profile →
• Investigators choice single agent — full drug profile →

Conditions studied

• Mantle Cell Lymphoma — all drugs for Mantle Cell Lymphoma →
• Lymphoma, Mantle-Cell — all drugs for Lymphoma, Mantle-Cell →

Sponsor

Celgene — full company profile →

Who can join

18 and older, any sex, with Mantle Cell Lymphoma or Lymphoma, Mantle-Cell. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Kaplan Meier Estimate for Progression Free Survival (PFS) by Independent Review Committee (IRC) Central Review Primary · From randomization to progression of disease or death; up to data cut off date of 07 March 2014; overall median follow-up time was 93.9 weeks

PFS was defined as time of randomization to the first observation of disease progression or death due to any cause, whichever was first. If a participant had not progressed or died, PFS was censored at the time of last assessment when the participant was known not to have progressed. For participants who received other anti-lymphoma therapy with no evidence of progression, PFS was censored at time of last tumor assessment with no evidence of progression prior to the start of new anti-lymphoma treatment.

Group	Value	95% CI
Lenalidomide	37.6	24.0 – 52.6
Investigators Choice	22.7	15.9 – 30.1

Kaplan Meier Estimate for Progression Free Survival by Investigator's Assessment at the Final Analysis Primary · From randomization to progression of disease or death; up to study discontinuation of 09 October 2018; overall median follow-up time was 285 weeks

Kaplan Meier estimates of PFS were defined as the time from randomization to the first observation of disease progression or death due to any cause, whichever was first. If a participant had not progressed or died, PFS was censored at the time of last completed assessment when the participant was known not to have progressed. For participants who received other anti-lymphoma therapy with no evidence of progression, PFS was censored at time of last tumor assessment with no evidence of progression prior to the start of new anti-lymphoma treatment.

Group	Value	95% CI
Lenalidomide	37.3	24.1 – 52.6
Investigators Choice	23.6	15.9 – 33.3

Percentage of Participants Who Achieved an Overall Response According to the IRC Central Review Secondary · From date of randomization to the data cut-off date of 07 March 2014; median treatment duration was 24.3 weeks for the lenalidomide arm and 13.1 weeks for the investigators choice arm

Overall Response Rate (ORR) was defined as the percentage of participants whose best response was Complete Response (CR), Complete Response unconfirmed (CRu) or Partial Response (PR). Participants who discontinued before any response had been observed or changed to other anti-lymphoma treatments before response had been observed, were considered as non-responders. Tumor Response was assessed by a modification of the International Lymphoma Workshop Response Criteria, IWRC, Cheson, 1999; CR is defined as the disappearance of all clinical and radiographic evidence of disease; CRu is defined as a

Group	Value	95% CI
Lenalidomide	40.0	32.58 – 47.78
Investigators Choice	10.7	5.02 – 19.37

Percentage of Participants Who Achieved an Overall Response as Assessed by the Investigator at the Final Analysis Secondary · From date of randomization to the study discontinuation date of 09 October 2018; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm

Overall Response Rate (ORR) was defined as the percentage of participants whose best response was Complete Response, Complete Response unconfirmed or Partial Response. Participants who had discontinued before any response has been observed or changed to other anti-lymphoma treatments before response had been observed, were considered as non-responders. Tumor Response was assessed by a modification of the International Lymphoma Workshop Response Criteria, IWRC, Cheson, 1999; CR is defined as the disappearance of all clinical and radiographic evidence of disease; CRu is defined as a CR, with a 1

Group	Value	95% CI
Lenalidomide	45.9	38.23 – 53.68
Investigators Choice	22.6	14.20 – 33.05

Kaplan Meier Estimate for Duration of Response (DOR) According to the IRC Central Review Secondary · From date of randomization to the data cut-off date of 07 March 2014; median study duration was 70.7 weeks for the lenalidomide arm and 69.3 weeks for the investigators choice arm

Duration of response was defined as the time from when the first response of CR, CRu, or PR was first achieved until documented tumor progression, or until the participant died from any cause, whichever occurred first. Participants who did not progress or die at the time of analysis were censored at the last assessment date that the participant was known to be progression-free. Participants who received a new treatment without documented progression were censored at the last assessment date that the participant was known to be progression-free.

Group	Value	95% CI
Lenalidomide	69.6	41.1 – 86.7
Investigators Choice	45.1	36.3 – 80.9

Kaplan Meier Estimate for Duration of Response as Assessed by the Investigator at the Final Analysis Secondary · From date of randomization to the study discontinuation date of 09 October 2018; median study duration was 103.9 weeks for lenalidomide and 87.0 weeks for the investigator choice arm

Duration of response was defined as the time from when the first response of CR, CRu, or PR was first achieved until documented tumor progression, or until the participant died from any cause, whichever occurred first. Participants who did not progress or die at the time of analysis were censored at the last assessment date that the participant was known to be progression-free. Participants who received a new treatment without documented progression were censored at the last assessment date that the participant was known to be progression-free.

Group	Value	95% CI
Lenalidomide	70.1	47.0 – 98.0
Investigators Choice	91.7	28.3 – 130.1

Percentage of Participants With a Complete Response, Unconfirmed Complete Response, Partial Response and Stable Disease According to the IRC Central Review Secondary · From date of randomization to the data cut-off date of 07 March 2014; median treatment duration was 24.3 weeks for the lenalidomide arm and 13.1 weeks for the investigators choice arm

Tumor control rate was defined as the percentage of participants with a complete response (CR), unconfirmed complete response (CRu), partial response (PR) and stable disease (SD). Tumor Response was assessed by a modification of the International Lymphoma Workshop Response Criteria, IWRC, Cheson, 1999); CR is defined as the disappearance of all clinical and radiographic evidence of disease; CRu is defined as a CR, with a 1) residual lymph node mass \>1.5 cm that has decreased by 75% in the sum of the product of the diameters (SPD). Individual nodes previously confluent decreased by more than 7

Group	Value	95% CI
Lenalidomide	69.4	61.89 – 76.24
Investigators Choice	63.1	51.87 – 73.37

Percentage of Participants With a Complete Response, Unconfirmed Complete Response, Partial Response and Stable Disease at the Final Analysis Secondary · From date of randomization to the discontinuation date of 09 October 2018; median treatment duration was 24.3 weeks for the lenalidomide arm and 13.1 weeks for the investigators choice arm

Tumor control rate was defined as the percentage of participants with a complete response (CR), unconfirmed complete response (CRu), partial response (PR) and stable disease (SD). Tumor Response was assessed by a modification of the International Lymphoma Workshop Response Criteria, IWRC, Cheson, 1999); CR is defined as the disappearance of all clinical and radiographic evidence of disease; CRu is defined as a CR, with a 1) residual lymph node mass \>1.5 cm that has decreased by 75% in the sum of the product of the diameters (SPD). Individual nodes previously confluent decreased by more than 7

Group	Value	95% CI
Lenalidomide	70.0	62.51 – 76.78
Investigators Choice	65.5	54.31 – 75.52

Kaplan Meier Estimate of Time to Progression According to the IRC Central Review Secondary · From date of randomization to the data cut-off date of 07 March 2014; median study duration was 70.7 weeks for the lenalidomide arm and 69.3 weeks for the investigators choice arm

Time to progression (TTP) was defined as the time from randomization until objective tumor progression. Time to progression did not include deaths. Participants without progression at the time of analysis were censored at the last assessment date that the participant was known to be progression-free. Participants who received a new anti-lymphoma treatment without documented progression were censored at the last assessment date that the participant was known to be progression-free.

Group	Value	95% CI
Lenalidomide	39.3	24.3 – 52.9
Investigators Choice	24.7	15.9 – 30.1

Kaplan Meier Estimate of Time to Progression as Assessed by the Investigator at the Final Analysis Secondary · From date of randomization to the study discontinuation date of 09 October 2018; median study duration was 103.9 weeks for lenalidomide and 87.0 weeks for the investigator choice arm

Time to progression (TTP) was defined as the time from randomization until objective tumor progression. Time to progression did not include deaths. Participants without progression at the time of analysis were censored at the last assessment date that the participant was known to be progression-free. Participants who received a new anti-lymphoma treatment without documented progression were censored at the last assessment date that the participant was known to be progression-free.

Group	Value	95% CI
Lenalidomide	39.3	25.1 – 61.0
Investigators Choice	24.7	15.9 – 36.7

Kaplan Meier Estimate of Time to Treatment Failure (TTF) as Assessed by the Investigator Secondary · From the date of the first treatment to the data cut-off date of 07 March 2014; median treatment duration was 24.3 weeks for the lenalidomide arm and 13.1 weeks for the investigators choice arm

Time to treatment failure was defined as the time from the first dose of study drug to discontinuation of treatment for any reason, including disease progression assessed by the investigator, treatment toxicity, or death. Participants who were on-treatment or completed the treatment according to the protocol were censored at the last date of drug intake.

Group	Value	95% CI
Lenalidomide	24.4	17.1 – 37.6
Investigators Choice	17.9	14.1 – 24.9

Kaplan Meier Estimate of Time to Treatment Failure as Assessed by the Investigator at the Final Analysis Secondary · From date of first dose of treatment to the study discontinuation date of 09 October 2018; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigator choice arm

Time to treatment failure was defined as the time from the first dose of study drug to discontinuation of treatment for any reason, including disease progression assessed by the investigator, treatment toxicity, or death. Participants who were on-treatment or completed the treatment according to the protocol were censored at the last date of drug intake.

Group	Value	95% CI
Lenalidomide	24.4	17.1 – 37.6
Investigators Choice	17.9	14.1 – 24.9

Adverse events — posted to ClinicalTrials.gov

Time frame: From randomization of study drug to 30 days post-last dose; up to the study discontinuation date of 09 October 2018; median treatment duration was 24.3 weeks for lenalidomide and 13.1 weeks for the investigators choice arm.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Lenalidomide

Serious: 75/167 (45%)

Deaths: 119/167

Investigator's Choice

Serious: 22/83 (27%)

Deaths: 59/83

Serious adverse events (118 terms)

Reaction	System	Lenalidomide	Investigator's Choice
ANAEMIA	Blood and lymphatic system disorders	—	—
FEBRILE NEUTROPENIA	Blood and lymphatic system disorders	—	—
NEUTROPENIA	Blood and lymphatic system disorders	—	—
DIARRHOEA	Gastrointestinal disorders	—	—
PNEUMONIA	Infections and infestations	—	—
PULMONARY EMBOLISM	Respiratory, thoracic and mediastinal disorders	—	—
PYREXIA	General disorders	—	—
THROMBOCYTOPENIA	Blood and lymphatic system disorders	—	—
GENERAL PHYSICAL HEALTH DETERIORATION	General disorders	—	—
LOWER RESPIRATORY TRACT INFECTION	Infections and infestations	—	—
ACUTE LYMPHOCYTIC LEUKAEMIA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
MANTLE CELL LYMPHOMA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
DYSPNOEA	Respiratory, thoracic and mediastinal disorders	—	—
CARDIAC ARREST	Cardiac disorders	—	—
CARDIAC FAILURE	Cardiac disorders	—	—
VOMITING	Gastrointestinal disorders	—	—
MULTIPLE ORGAN DYSFUNCTION SYNDROME	General disorders	—	—
BRONCHITIS	Infections and infestations	—	—
LUNG INFECTION	Infections and infestations	—	—
URINARY TRACT INFECTION	Infections and infestations	—	—
BASAL CELL CARCINOMA	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
SQUAMOUS CELL CARCINOMA OF SKIN	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
PLEURAL EFFUSION	Respiratory, thoracic and mediastinal disorders	—	—
HYPOTENSION	Vascular disorders	—	—
AUTOIMMUNE HAEMOLYTIC ANAEMIA	Blood and lymphatic system disorders	—	—

Other adverse events (41 terms — click to expand)

Reaction	System	Lenalidomide	Investigator's Choice
NEUTROPENIA	Blood and lymphatic system disorders	—	—
THROMBOCYTOPENIA	Blood and lymphatic system disorders	—	—
ANAEMIA	Blood and lymphatic system disorders	—	—
DIARRHOEA	Gastrointestinal disorders	—	—
FATIGUE	General disorders	—	—
LEUKOPENIA	Blood and lymphatic system disorders	—	—
CONSTIPATION	Gastrointestinal disorders	—	—
ASTHENIA	General disorders	—	—
PYREXIA	General disorders	—	—
NASOPHARYNGITIS	Infections and infestations	—	—
UPPER RESPIRATORY TRACT INFECTION	Infections and infestations	—	—
DECREASED APPETITE	Metabolism and nutrition disorders	—	—
COUGH	Respiratory, thoracic and mediastinal disorders	—	—
RASH	Skin and subcutaneous tissue disorders	—	—
NAUSEA	Gastrointestinal disorders	—	—
ABDOMINAL PAIN	Gastrointestinal disorders	—	—
OEDEMA PERIPHERAL	General disorders	—	—
BACK PAIN	Musculoskeletal and connective tissue disorders	—	—
BRONCHITIS	Infections and infestations	—	—
HYPOKALAEMIA	Metabolism and nutrition disorders	—	—
TUMOUR FLARE	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
PRURITUS	Skin and subcutaneous tissue disorders	—	—
HYPERTENSION	Vascular disorders	—	—
HEADACHE	Nervous system disorders	—	—
MUSCLE SPASMS	Musculoskeletal and connective tissue disorders	—	—
PAIN IN EXTREMITY	Musculoskeletal and connective tissue disorders	—	—
ARTHRALGIA	Musculoskeletal and connective tissue disorders	—	—
RESPIRATORY TRACT INFECTION	Infections and infestations	—	—
PARAESTHESIA	Nervous system disorders	—	—
DYSPNOEA	Respiratory, thoracic and mediastinal disorders	—	—
VERTIGO	Ear and labyrinth disorders	—	—
DYSPEPSIA	Gastrointestinal disorders	—	—
VOMITING	Gastrointestinal disorders	—	—
CONJUNCTIVITIS	Infections and infestations	—	—
INFLUENZA	Infections and infestations	—	—
HYPOALBUMINAEMIA	Metabolism and nutrition disorders	—	—
INSOMNIA	Psychiatric disorders	—	—
DERMATITIS ALLERGIC	Skin and subcutaneous tissue disorders	—	—
LYMPHOPENIA	Blood and lymphatic system disorders	—	—
ALANINE AMINOTRANSFERASE INCREASED	Investigations	—	—

Most-reported serious reactions: ANAEMIA, FEBRILE NEUTROPENIA, NEUTROPENIA, DIARRHOEA, PNEUMONIA, PULMONARY EMBOLISM, PYREXIA, THROMBOCYTOPENIA.

Data from ClinicalTrials.gov NCT00875667 adverse events section.

Sponsor's own description

To evaluate the safety and efficacy of lenalidomide versus investigator choice in patients with relapsed or refractory mantle cell lymphoma.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Lenalidomide versus investigator's choice in relapsed or refractory mantle cell lymphoma (MCL-002; SPRINT): a phase 2, randomised, multicentre trial.
   Trněný M, Lamy T, Walewski J, Belada D, et al · · 2016 · cited 119× · PMID 26899778 · DOI 10.1016/s1470-2045(15)00559-8
2. Activity of lenalidomide in mantle cell lymphoma can be explained by NK cell-mediated cytotoxicity.
   Hagner PR, Chiu H, Ortiz M, Apollonio B, et al · · 2017 · cited 40× · PMID 28771673 · DOI 10.1111/bjh.14866
3. Beyond Bruton's tyrosine kinase inhibitors in mantle cell lymphoma: bispecific antibodies, antibody-drug conjugates, CAR T-cells, and novel agents.
   Jain N, Mamgain M, Chowdhury SM, Jindal U, et al · · 2023 · cited 19× · PMID 37626420 · DOI 10.1186/s13045-023-01496-4
4. Local Investigators Significantly Overestimate Overall Response Rates Compared to Blinded Independent Central Reviews in Uncontrolled Oncology Trials: A Comprehensive Review of the Literature.
   Dello Russo C, Navarra P. · · 2022 · cited 8× · PMID 35652050 · DOI 10.3389/fphar.2022.858354
5. Prospective subgroup analyses of the randomized MCL-002 (SPRINT) study: lenalidomide versus investigator's choice in relapsed or refractory mantle cell lymphoma.
   Arcaini L, Lamy T, Walewski J, Belada D, et al · · 2018 · cited 8× · PMID 29193019 · DOI 10.1111/bjh.15025
6. Therapeutic Activity of Lenalidomide in Mantle Cell Lymphoma and Indolent Non-Hodgkin's Lymphomas.
   Gunnellini M, Falchi L. · · 2012 · cited 6× · PMID 22761620 · DOI 10.1155/2012/523842
7. Patients' and physicians' disagreement on patients' understanding of clinical cancer trial information: a pairwise pilot study of mirroring subjective assessments compared with objective measurements.
   Dellson P, Carlsson C, Nilbert M, Jernström H. · · 2019 · cited 4× · PMID 31142346 · DOI 10.1186/s13063-019-3416-2
8. Efficacy and safety of lenalidomide in the treatment of B-cell non-Hodgkin lymphoma.
   Liu Y, Li Y, Zhang C, Yang X, et al · · 2024 · cited 1× · PMID 38578513 · DOI 10.1007/s12672-024-00965-7