Consortium study falls short of expectations

SAN FRANCISCO—A group’s effort to identify optimal front-line treatment for peripheral T-cell lymphomas (PTCLs) was not as successful as researchers anticipated.

The North American PTCL Consortium set out to find a treatment that could best CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone), as studies have suggested this regimen is inadequate for patients with PTCL.

So the group organized a trial testing

a potentially more promising regimen: cyclophosphamide, etoposide, vincristine, and prednisone, alternating with pralatrexate (CEOP-P).

However, CEOP-P elicited a complete response (CR) rate comparable to rates historically seen with CHOP, and progression-free survival rates with the new regimen were “not particularly encouraging.”

Ranjana Advani, MD, of Stanford University Medical Center in California, discussed this trial’s inception, execution, and results at the 6th Annual T-cell Lymphoma Forum.

Trial inception

It all began with the first meeting of the North American PTCL Consortium, which took place at the 2006 ASH Annual Meeting. Physicians from 17 centers gathered to discuss the state of PTCL research in North America.

The group realized there were too many open studies for such a rare disease, and efforts should be more focused. However, they could not agree publicly as to which studies should get priority, so they used an anonymous survey to obtain a consensus.

Survey responses were “all over the map,” Dr Advani said. But ultimately, the consensus was that ongoing trials were not sufficient, and a new trial was necessary.

The group decided to first lend their support to ongoing trials and then launch a new study. At the fourth and fifth meetings of the North American PTCL Consortium (both in 2009), they drafted the concept of a front-line trial testing CEOP-P.

“We decided to use [CEOP] as a backbone because there were reservations about anthracyclines having a role in PTCL, and there was data . . . in patients [with B-cell lymphomas] who were not anthracycline-eligible and did reasonably well when etoposide was substituted [for hydroxydaunorubicin],” Dr Advani said.

As for for the second “P” in CEOP-P, pralatrexate was the first drug approved for patients with relapsed PTCL, which provided the rationale for evaluating it in the front-line setting.

Execution and results

The primary aim of this study was to improve the CR rate from 40% to 60% with CEOP-P followed by optional transplant. A literature review had revealed that CRs with CHOP have been in the range of 40% to 50%.

The researchers enrolled a total of 34 patients, but 1 withdrew consent. Twenty-seven patients received at least 2 cycles of CEOP-P. Of the 6 patients who received a single cycle, 4 discontinued treatment due to early disease progression, and 2 discontinued because of adverse events.

Grade 3-4 adverse events associated with CEOP-P included anemia, thrombocytopenia, febrile neutropenia, mucositis, sepsis, increased creatinine, and liver transaminases.

The researchers had used a 2-stage Simon design (alpha=0.10, 90% power) to test the null hypothesis that the CR rate would be 40% or greater.

For the first stage of 20 evaluable patients, the trial would be terminated if 8 or fewer patients experienced a CR after course 2B of chemotherapy. For the second stage, 34 patients were required, and at least 17 had to achieve a CR at the end of therapy for the regimen to be considered useful.

At the end of stage 1, 50% of the patients (10/20) had achieved a CR. Ultimately, 52% of all patients (n=17) achieved a CR.

This suggests CEOP-P is a useful regimen, according to the study design. But the primary aim of improving CR from 40% to 60% was not met.

Furthermore, the estimated 1-year and 2-year progression-free survival rates were “not particularly encouraging,” according to Dr Advani. The rates were 50% and 34%, respectively. And the estimated 1-year and 2-year overall survival rate was 64%.

“So this was a lesson in working together and getting a trial from ground zero, to up and running, to a presentation, and publication underway,” Dr Advani said.

“And even though it took in all the ingredients of what everybody thought was important . . . , it’s not a regimen which has that much promise to move to a randomized setting. And so defining the optimal front-line therapy in PTCL continues to be a challenge and an unmet need.”

Now, the North American PTCL Consortium is working on a second front-line trial testing cyclophosphamide, hydroxydaunorubicin, vincristine, etoposide, and prednisone (CHOEP) plus lenalidomide in stage II, III, and IV PTCL. The final protocol has been circulated, and the group anticipates the first patient will be enrolled by June or July of this year.

Dr Advani and her colleagues also presented results of the CEOP-P trial at the 2013 ASH Annual Meeting as abstract 3044. (Information in the abstract differs from that presented at the T-cell Lymphoma Forum.)

SAN FRANCISCO—A group’s effort to identify optimal front-line treatment for peripheral T-cell lymphomas (PTCLs) was not as successful as researchers anticipated.

The North American PTCL Consortium set out to find a treatment that could best CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone), as studies have suggested this regimen is inadequate for patients with PTCL.

So the group organized a trial testing

a potentially more promising regimen: cyclophosphamide, etoposide, vincristine, and prednisone, alternating with pralatrexate (CEOP-P).

However, CEOP-P elicited a complete response (CR) rate comparable to rates historically seen with CHOP, and progression-free survival rates with the new regimen were “not particularly encouraging.”

Ranjana Advani, MD, of Stanford University Medical Center in California, discussed this trial’s inception, execution, and results at the 6th Annual T-cell Lymphoma Forum.

Trial inception

It all began with the first meeting of the North American PTCL Consortium, which took place at the 2006 ASH Annual Meeting. Physicians from 17 centers gathered to discuss the state of PTCL research in North America.

The group realized there were too many open studies for such a rare disease, and efforts should be more focused. However, they could not agree publicly as to which studies should get priority, so they used an anonymous survey to obtain a consensus.

Survey responses were “all over the map,” Dr Advani said. But ultimately, the consensus was that ongoing trials were not sufficient, and a new trial was necessary.

The group decided to first lend their support to ongoing trials and then launch a new study. At the fourth and fifth meetings of the North American PTCL Consortium (both in 2009), they drafted the concept of a front-line trial testing CEOP-P.

“We decided to use [CEOP] as a backbone because there were reservations about anthracyclines having a role in PTCL, and there was data . . . in patients [with B-cell lymphomas] who were not anthracycline-eligible and did reasonably well when etoposide was substituted [for hydroxydaunorubicin],” Dr Advani said.

As for for the second “P” in CEOP-P, pralatrexate was the first drug approved for patients with relapsed PTCL, which provided the rationale for evaluating it in the front-line setting.

Execution and results

The primary aim of this study was to improve the CR rate from 40% to 60% with CEOP-P followed by optional transplant. A literature review had revealed that CRs with CHOP have been in the range of 40% to 50%.

The researchers enrolled a total of 34 patients, but 1 withdrew consent. Twenty-seven patients received at least 2 cycles of CEOP-P. Of the 6 patients who received a single cycle, 4 discontinued treatment due to early disease progression, and 2 discontinued because of adverse events.

Grade 3-4 adverse events associated with CEOP-P included anemia, thrombocytopenia, febrile neutropenia, mucositis, sepsis, increased creatinine, and liver transaminases.

The researchers had used a 2-stage Simon design (alpha=0.10, 90% power) to test the null hypothesis that the CR rate would be 40% or greater.

For the first stage of 20 evaluable patients, the trial would be terminated if 8 or fewer patients experienced a CR after course 2B of chemotherapy. For the second stage, 34 patients were required, and at least 17 had to achieve a CR at the end of therapy for the regimen to be considered useful.

At the end of stage 1, 50% of the patients (10/20) had achieved a CR. Ultimately, 52% of all patients (n=17) achieved a CR.

This suggests CEOP-P is a useful regimen, according to the study design. But the primary aim of improving CR from 40% to 60% was not met.

Furthermore, the estimated 1-year and 2-year progression-free survival rates were “not particularly encouraging,” according to Dr Advani. The rates were 50% and 34%, respectively. And the estimated 1-year and 2-year overall survival rate was 64%.

“So this was a lesson in working together and getting a trial from ground zero, to up and running, to a presentation, and publication underway,” Dr Advani said.

“And even though it took in all the ingredients of what everybody thought was important . . . , it’s not a regimen which has that much promise to move to a randomized setting. And so defining the optimal front-line therapy in PTCL continues to be a challenge and an unmet need.”

Now, the North American PTCL Consortium is working on a second front-line trial testing cyclophosphamide, hydroxydaunorubicin, vincristine, etoposide, and prednisone (CHOEP) plus lenalidomide in stage II, III, and IV PTCL. The final protocol has been circulated, and the group anticipates the first patient will be enrolled by June or July of this year.

Dr Advani and her colleagues also presented results of the CEOP-P trial at the 2013 ASH Annual Meeting as abstract 3044. (Information in the abstract differs from that presented at the T-cell Lymphoma Forum.)

SAN FRANCISCO—A group’s effort to identify optimal front-line treatment for peripheral T-cell lymphomas (PTCLs) was not as successful as researchers anticipated.

The North American PTCL Consortium set out to find a treatment that could best CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone), as studies have suggested this regimen is inadequate for patients with PTCL.

So the group organized a trial testing

a potentially more promising regimen: cyclophosphamide, etoposide, vincristine, and prednisone, alternating with pralatrexate (CEOP-P).

However, CEOP-P elicited a complete response (CR) rate comparable to rates historically seen with CHOP, and progression-free survival rates with the new regimen were “not particularly encouraging.”

Ranjana Advani, MD, of Stanford University Medical Center in California, discussed this trial’s inception, execution, and results at the 6th Annual T-cell Lymphoma Forum.

Trial inception

It all began with the first meeting of the North American PTCL Consortium, which took place at the 2006 ASH Annual Meeting. Physicians from 17 centers gathered to discuss the state of PTCL research in North America.

The group realized there were too many open studies for such a rare disease, and efforts should be more focused. However, they could not agree publicly as to which studies should get priority, so they used an anonymous survey to obtain a consensus.

Survey responses were “all over the map,” Dr Advani said. But ultimately, the consensus was that ongoing trials were not sufficient, and a new trial was necessary.

The group decided to first lend their support to ongoing trials and then launch a new study. At the fourth and fifth meetings of the North American PTCL Consortium (both in 2009), they drafted the concept of a front-line trial testing CEOP-P.

“We decided to use [CEOP] as a backbone because there were reservations about anthracyclines having a role in PTCL, and there was data . . . in patients [with B-cell lymphomas] who were not anthracycline-eligible and did reasonably well when etoposide was substituted [for hydroxydaunorubicin],” Dr Advani said.

As for for the second “P” in CEOP-P, pralatrexate was the first drug approved for patients with relapsed PTCL, which provided the rationale for evaluating it in the front-line setting.

Execution and results

The primary aim of this study was to improve the CR rate from 40% to 60% with CEOP-P followed by optional transplant. A literature review had revealed that CRs with CHOP have been in the range of 40% to 50%.

The researchers enrolled a total of 34 patients, but 1 withdrew consent. Twenty-seven patients received at least 2 cycles of CEOP-P. Of the 6 patients who received a single cycle, 4 discontinued treatment due to early disease progression, and 2 discontinued because of adverse events.

Grade 3-4 adverse events associated with CEOP-P included anemia, thrombocytopenia, febrile neutropenia, mucositis, sepsis, increased creatinine, and liver transaminases.

The researchers had used a 2-stage Simon design (alpha=0.10, 90% power) to test the null hypothesis that the CR rate would be 40% or greater.

For the first stage of 20 evaluable patients, the trial would be terminated if 8 or fewer patients experienced a CR after course 2B of chemotherapy. For the second stage, 34 patients were required, and at least 17 had to achieve a CR at the end of therapy for the regimen to be considered useful.

At the end of stage 1, 50% of the patients (10/20) had achieved a CR. Ultimately, 52% of all patients (n=17) achieved a CR.

This suggests CEOP-P is a useful regimen, according to the study design. But the primary aim of improving CR from 40% to 60% was not met.

Furthermore, the estimated 1-year and 2-year progression-free survival rates were “not particularly encouraging,” according to Dr Advani. The rates were 50% and 34%, respectively. And the estimated 1-year and 2-year overall survival rate was 64%.

“So this was a lesson in working together and getting a trial from ground zero, to up and running, to a presentation, and publication underway,” Dr Advani said.

“And even though it took in all the ingredients of what everybody thought was important . . . , it’s not a regimen which has that much promise to move to a randomized setting. And so defining the optimal front-line therapy in PTCL continues to be a challenge and an unmet need.”

Now, the North American PTCL Consortium is working on a second front-line trial testing cyclophosphamide, hydroxydaunorubicin, vincristine, etoposide, and prednisone (CHOEP) plus lenalidomide in stage II, III, and IV PTCL. The final protocol has been circulated, and the group anticipates the first patient will be enrolled by June or July of this year.

Dr Advani and her colleagues also presented results of the CEOP-P trial at the 2013 ASH Annual Meeting as abstract 3044. (Information in the abstract differs from that presented at the T-cell Lymphoma Forum.)