Lymphoblastic LymphomaPhase 2NCT01451515
NHL16: Study For Newly Diagnosed Patients With Acute Lymphoblastic Lymphoma
A Phase 2 study testing Prednisone, Vincristine and Daunorubicin in people with Lymphoblastic Lymphoma, run by St. Jude Children's Research Hospital at 2 sites in United States.
Trial summary
This is a phase II clinical trial using risk-adapted therapy. The treatment is acute lymphoblastic leukemia (ALL)-based therapy, using multi-agent regimens comprising of induction, consolidation, and continuation (maintenance) phases delivered over 24-30 months. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Lymphoblastic Lymphoma
- What is being tested?
- Prednisone, Vincristine and Daunorubicin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 2 sitesUnited States
- Study dates
- 25 May 2012to 31 May 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis of newly diagnosed lymphoblastic lymphoma (patients must have <25% tumor cells in bone marrow by morphology)
- Age ≤ 21 years
- Limited prior therapy, including systemic glucocorticoids for 1 week or less, 1 dose of vincristine, emergency radiation therapy to the mediastinum, and 1 dose of IT chemotherapy. Other circumstances must be cleared by PI or co-PI.
- Written, informed consent and assent following guidelines of the Institutional Review Board, National Cancer Institute (NCI), Food and Drug Administration (FDA), and Office of Human Research Protections (OHRP).
Who cannot join
- Participants with prior therapy, other than therapy specified in 3 above.
- Participants who are pregnant or lactating.
- Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Rady Children's Hospital San Diego
San Diego, California, 92123
About this study
This is a phase II clinical trial using risk-adapted therapy. The treatment is acute lymphoblastic leukemia (ALL)-based therapy, using multi-agent regimens comprising of induction, consolidation, and continuation (maintenance) phases delivered over 24-30 months. Participants will be classified into 3 treatment stratums, based on bone marrow/peripheral blood lymphoma cells involvement at diagnosis and day 8 for T-lymphoblastic lymphoma and bone marrow/peripheral blood lymphoma cells involvement at diagnosis for B-lymphoblastic lymphoma.
The Primary Objective of this study is:
Read more
To improve the outcome of children with lymphoblastic lymphoma (LL) who have minimal disseminated disease (MDD) equal to or more than 1% at diagnosis by using MDD- and minimal residual disease (MRD)- based risk-adapted therapy.
The Secondary Objectives of this study are:
- To estimate the event-free survival and overall survival of children with lymphoblastic lymphoma who are treated with MDD- or MRD-based risk- directed therapy.
- To evaluate the prognostic value of levels of MDD at diagnosis and MRD on day 8 of remission induction.
Read the detailed description
TREATMENT PLAN
Treatment will consist of 3 main phases: remission induction, consolidation [only for patients with any central nervous system (CNS) disease and/or testicular involvement], and continuation.
- Induction (6-7 weeks).
- Consolidation for participants with CNS involvement or those with testicular disease only (10 weeks).
- Reintensification - Participants with residual disease any time after induction therapy may receive 1-2 cycles of re-intensification therapy and may proceed to allogeneic stem cell transplant if suitable donor is available.
- Continuation Therapy (98-120 weeks).
- Intrathecal Chemotherapy (days 1 and 15; if needed also on days 8 and 22)
TREATMENT SCHEME
T lymphoblastic lymphoma: bone marrow/peripheral blood (BM/PB) involvement (MDD/MRD): Diagnosis: less than 1%; Day 8: +/- (Stratum 1)
- Induction
- Single dose of Cyclophosphamide
- Steroid: prednisone
- Continuation: 98 weeks
T lymphoblastic lymphoma: BM/PB involvement (MDD/MRD): Diagnosis: equal to or greater than 1%; Day 8: - (Stratum 2)
- Induction
- Fractionated Cyclophosphamide
- Steroid: prednisone
- Continuation : 98 weeks
T lymphoblastic lymphoma: BM/PB involvement (MDD/MRD): Diagnosis: equal to or greater than 1%; Day 8: + (Stratum 3)
- Induction
- Fractionated Cyclophosphamide
- Steroid: prednisone and dexamethasone
- Continuation: 120 weeks
B lymphoblastic lymphoma: Stage I-III (Stratum 1)
- Induction
- Single dose of Cyclophosphamide
- Steroid: prednisone
- Continuation: 98 weeks
B lymphoblastic lymphoma: Stage IV or testicular (Stratum 2)
- Induction
- Fractionated Cyclophosphamide
- Steroid: prednisone
- Continuation: 98 weeks
Patients with CNS or testicular involvement will receive Consolidation therapy prior to continuation therapy and receive extended maintenance therapy (120 weeks).
Any patient with detectable disease (MRD, bone marrow or biopsy of residual mass) at the end of induction may be considered for reintensification and/or hematopoietic stem cell transplantation (HSCT).
- Conditions
- Lymphoblastic Lymphoma
- Being tested
- Prednisone, Vincristine, Daunorubicin, PEG-asparaginase, Erwinia asparaginase
- Keywords
- Lymphoblastic lymphoma
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PrednisoneDrug
Also called Prednisolone
Given orally (PO).
VincristineDrug
Also called Oncovin®, Vincristine sulfate
Given intravenously (IV).
DaunorubicinDrug
Also called Daunomycin, Cerubidine®
Given IV.
PEG-asparaginaseDrug
Also called Pegaspargase, Oncaspar®
Given intramuscularly (IM) or IV.
Erwinia asparaginaseDrug
Also called Erwinase®
Given IM or IV if allergy occurs with the first or second PEG-asparaginase dose.
DoxorubicinDrug
Also called Adriamycin®
Given IV.
CyclophosphamideDrug
Also called Cytoxan®
Given IV.
CytarabineDrug
Also called Ara-C, Cytosar-U®
Given IV or IT.
ThioguanineDrug
Also called Purine antimetabolite
Given PO.
ClofarabineDrug
Also called Cl-F-Ara-A, CAFdA, 2-Chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-9H-purin-6-amine, Clofarex
Given IV.
MethotrexateDrug
Also called MTX, High-dose methotrexate (HD-MTX)
Given IV, IM or IT.
MercaptopurineDrug
Also called 6-MP, Purinethol®
Given PO.
DexamethasoneDrug
Also called Decadron®
Given PO or IV.
HydrocortisoneDrug
Also called Cortef®
Given IT.
EtoposideDrug
Also called VP-16, Vepesid®
Given IV.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Patients will undergo treatment as described in the intervention section. Interventions include:
* Remission induction: prednisone, vincristine, daunorubicin, PEG-asparaginase (or Erwinia asparaginase), IT-MHA (Methotrexate, hydrocortisone, and cytarabine), cyclophosphamide, cytarabine, thioguanine
* Consolidation: PEG-asparaginase, High-dose methotrexate (HD-MTX), mercaptopurine
* Postremission continuation: Dexamethasone, doxorubicin, vincristine, mercaptopurine, PEG-asparaginase, cyclophosphamide, cytarabine, methotrexate
* Reintensification: dexamethasone, cytarabine, etoposide, PEG-asparaginase, clofarabine, cyclophosphamide
* All patients receive IT-MHA on days 1 and 15. Some patients also receive additional IT-MHA on days 8 and 22. Receives: Drug: Prednisone; Drug: Vincristine; Drug: Daunorubicin; Drug: PEG-asparaginase; Drug: Erwinia asparaginase; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Thioguanine; Drug: Clofarabine; Drug: Methotrexate; Drug: Mercaptopurine; Drug: Dexamethasone; Drug: Hydrocortisone; Drug: Etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Probability of Event-free Survival (EFS)
For EFS, relapse and second malignancies are considered as failures in addition to death in complete remission. The time to EFS will be set to 0 for patients who fail to achieve complete remission. Kaplan-Meier estimates of the OS and EFS curves are computed, along with estimates of standard errors by Peto's method.
Please note the unit of measurement of probabilities are percentages.
Measured: Two years post therapy.
Secondary outcomes (3)
Probability of Overall Survival (OS)
For OS, only deaths are considered failures for OS. Kaplan-Meier estimates of the OS curves are computed along with estimates of standard errors by Peto's method.
Please note the unit of measurement of probabilities are percentages.
Measured: Two years post therapy.
Minimal Disseminated Disease (MDD)
Detectable disease in bone marrow or blood: A binary measure, positive (detectable), negative (non-detectable)
Measured: At Diagnosis
Minimal Residual Disease (MRD)
Detectable disease in bone marrow or blood: A binary measure, positive (detectable), negative (non-detectable)
Measured: Day 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2011 (estimated)
- Study start25 May 2012
- Primary completion8 May 2021
- Study completion31 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Lymphoblastic LymphomaStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National University of Singapore
- Responsible party
- Sponsor
- Investigators
- Hiroto Inaba, MD,PhD, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01451515
- Sponsor's protocol ID
- NHL16
- Other IDs
- NCI-2012-00496
- Status last verified
- Jun 2022
- First submitted
- 17 Aug 2011
- Last updated
- 28 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NHL16: Study For Newly Diagnosed Patients With Acute Lymphoblastic Lymphoma
- ClinicalTrials.gov ID
- NCT01451515
- Acronym / sponsor ID
- NHL16
- Conditions
- Lymphoblastic Lymphoma
- Keywords
- Lymphoblastic lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Collaborators
- National University of Singapore
- Study start
- 25 May 2012 (actual)
- Primary completion
- 8 May 2021 (actual)
- Study completion
- 31 May 2022 (actual)
- First posted
- 13 Oct 2011 (estimated)
- Results
- Posted 23 May 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase II clinical trial using risk-adapted therapy. The treatment is acute lymphoblastic leukemia (ALL)-based therapy, using multi-agent regimens comprising of induction, consolidation, and continuation (maintenance) phases delivered over 24-30 months. Participants will be classified into 3 treatment stratums, based on bone marrow/peripheral blood lymphoma cells involvement at diagnosis and day 8 for T-lymphoblastic lymphoma and bone marrow/peripheral blood lymphoma cells involvement at diagnosis for B-lymphoblastic lymphoma.
The Primary Objective of this study is:
To improve the outcome of children with lymphoblastic lymphoma (LL) who have minimal disseminated disease (MDD) equal to or more than 1% at diagnosis by using MDD- and minimal residual disease (MRD)- based risk-adapted therapy.
The Secondary Objectives of this study are:
- To estimate the event-free survival and overall survival of children with lymphoblastic lymphoma who are treated with MDD- or MRD-based risk- directed therapy.
- To evaluate the prognostic value of levels of MDD at diagnosis and MRD on day 8 of remission induction.
Detailed description
TREATMENT PLAN
Treatment will consist of 3 main phases: remission induction, consolidation [only for patients with any central nervous system (CNS) disease and/or testicular involvement], and continuation.
- Induction (6-7 weeks).
- Consolidation for participants with CNS involvement or those with testicular disease only (10 weeks).
- Reintensification - Participants with residual disease any time after induction therapy may receive 1-2 cycles of re-intensification therapy and may proceed to allogeneic stem cell transplant if suitable donor is available.
- Continuation Therapy (98-120 weeks).
- Intrathecal Chemotherapy (days 1 and 15; if needed also on days 8 and 22)
TREATMENT SCHEME
T lymphoblastic lymphoma: bone marrow/peripheral blood (BM/PB) involvement (MDD/MRD): Diagnosis: less than 1%; Day 8: +/- (Stratum 1)
- Induction
- Single dose of Cyclophosphamide
- Steroid: prednisone
- Continuation: 98 weeks
T lymphoblastic lymphoma: BM/PB involvement (MDD/MRD): Diagnosis: equal to or greater than 1%; Day 8: - (Stratum 2)
- Induction
- Fractionated Cyclophosphamide
- Steroid: prednisone
- Continuation : 98 weeks
T lymphoblastic lymphoma: BM/PB involvement (MDD/MRD): Diagnosis: equal to or greater than 1%; Day 8: + (Stratum 3)
- Induction
- Fractionated Cyclophosphamide
- Steroid: prednisone and dexamethasone
- Continuation: 120 weeks
B lymphoblastic lymphoma: Stage I-III (Stratum 1)
- Induction
- Single dose of Cyclophosphamide
- Steroid: prednisone
- Continuation: 98 weeks
B lymphoblastic lymphoma: Stage IV or testicular (Stratum 2)
- Induction
- Fractionated Cyclophosphamide
- Steroid: prednisone
- Continuation: 98 weeks
Patients with CNS or testicular involvement will receive Consolidation therapy prior to continuation therapy and receive extended maintenance therapy (120 weeks).
Any patient with detectable disease (MRD, bone marrow or biopsy of residual mass) at the end of induction may be considered for reintensification and/or hematopoietic stem cell transplantation (HSCT).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: Prednisone, Drug: Vincristine, Drug: Daunorubicin, Drug: PEG-asparaginase, Drug: Erwinia asparaginase, Drug: Doxorubicin, Drug: Cyclophosphamide, Drug: Cytarabine, Drug: Thioguanine, Drug: Clofarabine, Drug: Methotrexate, Drug: Mercaptopurine, Drug: Dexamethasone, Drug: Hydrocortisone, Drug: EtoposidePatients will undergo treatment as described in the intervention section. Interventions include: * Remission induction: prednisone, vincristine, daunorubicin, PEG-asparaginase (or Erwinia asparaginase), IT-MHA (Methotrexate, hydrocortisone, and cytarabine), cyclophosphamide, cytarabine, thioguanine * Consolidation: PEG-asparaginase, High-dose methotrexate (HD-MTX), mercaptopurine * Postremission continuation: Dexamethasone, doxorubicin, vincristine, mercaptopurine, PEG-asparaginase, cyclophosphamide, cytarabine, methotrexate * Reintensification: dexamethasone, cytarabine, etoposide, PEG-asparaginase, clofarabine, cyclophosphamide * All patients receive IT-MHA on days 1 and 15. Some patients also receive additional IT-MHA on days 8 and 22. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Diagnosis of newly diagnosed lymphoblastic lymphoma (patients must have <25% tumor cells in bone marrow by morphology)
- Age ≤ 21 years
- Limited prior therapy, including systemic glucocorticoids for 1 week or less, 1 dose of vincristine, emergency radiation therapy to the mediastinum, and 1 dose of IT chemotherapy. Other circumstances must be cleared by PI or co-PI.
- Written, informed consent and assent following guidelines of the Institutional Review Board, National Cancer Institute (NCI), Food and Drug Administration (FDA), and Office of Human Research Protections (OHRP).
Key exclusion criteria (3 listed)
- Participants with prior therapy, other than therapy specified in 3 above.
- Participants who are pregnant or lactating.
- Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PrednisoneAlso: PrednisoloneGiven orally (PO). | Drug | Treatment |
| VincristineAlso: Oncovin®, Vincristine sulfateGiven intravenously (IV). | Drug | Treatment |
| DaunorubicinAlso: Daunomycin, Cerubidine®Given IV. | Drug | Treatment |
| PEG-asparaginaseAlso: Pegaspargase, Oncaspar®Given intramuscularly (IM) or IV. | Drug | Treatment |
| Erwinia asparaginaseAlso: Erwinase®Given IM or IV if allergy occurs with the first or second PEG-asparaginase dose. | Drug | Treatment |
| DoxorubicinAlso: Adriamycin®Given IV. | Drug | Treatment |
| CyclophosphamideAlso: Cytoxan®Given IV. | Drug | Treatment |
| CytarabineAlso: Ara-C, Cytosar-U®Given IV or IT. | Drug | Treatment |
| ThioguanineAlso: Purine antimetaboliteGiven PO. | Drug | Treatment |
| ClofarabineAlso: Cl-F-Ara-A, CAFdA, 2-Chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-9H-purin-6-amine, ClofarexGiven IV. | Drug | Treatment |
| MethotrexateAlso: MTX, High-dose methotrexate (HD-MTX)Given IV, IM or IT. | Drug | Treatment |
| MercaptopurineAlso: 6-MP, Purinethol®Given PO. | Drug | Treatment |
| DexamethasoneAlso: Decadron®Given PO or IV. | Drug | Treatment |
| HydrocortisoneAlso: Cortef®Given IT. | Drug | Treatment |
| EtoposideAlso: VP-16, Vepesid®Given IV. | Drug | Treatment |
Primary outcome
Probability of Event-free Survival (EFS)
Time frame: Two years post therapy.
For EFS, relapse and second malignancies are considered as failures in addition to death in complete remission. The time to EFS will be set to 0 for patients who fail to achieve complete remission. Kaplan-Meier estimates of the OS and EFS curves are computed, along with estimates of standard errors by Peto's method. Please note the unit of measurement of probabilities are percentages.
3 secondary outcomes
Probability of Overall Survival (OS)
Time frame: Two years post therapy.
Minimal Disseminated Disease (MDD)
Time frame: At Diagnosis
Minimal Residual Disease (MRD)
Time frame: Day 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- St. Jude Children's Research HospitalLink provided by the sponsor.
- Clinical Trials Open at St. JudeLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hiroto Inaba, MD,PhD principal investigator
St. Jude Children's Research Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Prednisone, Vincristine and Daunorubicin in people with Lymphoblastic Lymphoma, run by St. Jude Children's Research Hospital at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Probability of Event-free Survival (EFS) (time frame: Two years post therapy.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2022.