LeukemiaInterfant06NCT00550992
Different Therapies in Treating Infants With Newly Diagnosed Acute Leukemia
A study testing anti-thymocyte globulin, asparaginase and busulfan in people with Leukemia, run by Dutch Childhood Oncology Group at 13 sites in 9 countries.
Trial summary
RATIONALE: Giving chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. Read more about this study
- Who is it for?
- Ages Up to 1 year
- Conditions the study is for
- Leukemia
- What is being tested?
- anti-thymocyte globulin, asparaginase and busulfan
- Type of treatment
- Surgery or procedure
- How many people
- 445 participants
- Where
- 13 sitesin 9 countries
- Study dates
- Jan 2006to Dec 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 1 year
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Diagnosis of acute lymphoblastic leukemia (ALL) or biphenotypic leukemia meeting the following criteria:
- Based on European Group for the Classification of Acute Leukemia (EGIL) diagnostic criteria
- Newly diagnosed disease
- Verified by morphology and confirmed by cytochemistry and immunophenotyping
- Trephine biopsy is recommended (unless diagnosis can be confirmed by peripheral blood examination) in the event that bone marrow aspiration results in a "dry tap"
- Must have MLL gene rearrangements documented by split-signal fluorescence in situ hybridization and meets 1 of the following risk criteria:
Show all 24Show fewer
- Low-risk disease, defined as all MLL germline cases
- Medium-risk disease, defined by 1 of the following criteria:
- MLL status unknown
- MLL rearranged AND age > 6 months
- MLL rearranged AND age < 6 months AND WBC < 300 x 10^9/L AND prednisone good response
- High-risk disease, defined by MLL rearrangement AND meets the following criteria:
- Age at diagnosis < 6 months (i.e., < 183 days)
- WBC ≥ 300 x 10^9/L AND/OR prednisone poor response
- Minimum donor and stem cell requirements for high-risk patients undergoing stem cell transplantation:
- Donor meeting 1 of the following criteria:
- HLA-identical sibling
- Very well-matched related or unrelated donor
- Must be HLA compatible in 10/10 or 9/10 alleles by 4 digit/allele high-resolution molecular genotyping
- Stem cell source
- Bone marrow (preferred source) OR peripheral blood stem cells of filgrastim [G-CSF]-stimulated donors OR cord blood
- Highly-matched unrelated umbilical cord blood (UCB) (> 7/8 matches identified by high-resolution typing) accepted if a sibling donor is not able to donate bone marrow AND UCB with a sufficient number of nucleated cells (NCs) (i.e., > 1.5 x 10^7/kg recipient body weight [BW]) is cryopreserved
- Must have ≥ 3 x 10^8 NCs/kg BW OR 3 x 10^6/kg BW CD34-positive cells available for transplantation
- CNS or testicular leukemia at diagnosis allowed
Who cannot join
- Mature B-ALL, defined by the immunophenotypical presence of surface immunoglobulins or t(8;14) and breakpoint as in B-ALL
- Presence of the t(9;22) (q34;q11) or bcr-abl fusion in the leukemic cells (if data are not known, patient still may be eligible)
- Relapsed ALL
- PATIENT CHARACTERISTICS:
- See Disease Characteristics
- PRIOR CONCURRENT THERAPY:
- More than 4 weeks since prior systemic corticosteroids
- Corticosteroids by aerosol are allowed
Trial locations and contacts
13 sites in 9 countries.
13 sites in 9 countries
United States4 sites, 4 recruiting
- Recruiting
Children's Hospital Boston
Boston, Massachusetts, 02215
Lewis B. Silverman, MD, 617-632-5285
- Recruiting
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, 77030-4009
Clinical Trials Office - M. D. Anderson Cancer Center at the U, 713-792-3245
- Recruiting
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Clinical Trials Office - St. Jude Children's Research Hospital, 901-595-4644
- Recruiting
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, 98105
Blythe Thomson, MD, 206-987-2106
Germany2 sites, 2 recruiting
- Recruiting
University Medical Center Hamburg - Eppendorf
Hamburg, D-20246
Gritta Janka-Schaub, 49-404-2803-2580
- Recruiting
Medizinische Hochschule Hannover
Hanover, D-30625
Martin Schrappe, MD, PhD, 49-511-532-6713
Austria1 site, 1 recruiting
- Recruiting
St. Anna Children's Hospital
Vienna, A-1090
Georg Mann, MD, 43-1-4017-1250
Belgium1 site, 1 recruiting
- Recruiting
Hopital Universitaire Des Enfants Reine Fabiola
Brussels, 1020
Alice Ferster, MD, 32-2-477-2678, aferster@ulb.ac.be
Czechia1 site, 1 recruiting
- Recruiting
University Hospital Motol
Prague, 150 06
Jan Stary, MD, 420-2-2443-6401, jan.stary@lfmotol.cuni.cz
France1 site, 1 recruiting
- Recruiting
CHR Hotel Dieu
Nantes, 44093
Francoise Mechinaud, MD, 33-1-4249-9046
Italy1 site, 1 recruiting
- Recruiting
Nuovo Ospedale San Gerardo at University of Milano-Bicocca
Monza, 20052
Andrea Biondi, MD, 39-039-233-3661, biondi@galactica.it
Netherlands1 site, 1 recruiting
- Recruiting
Erasmus MC - Sophia Children's Hospital
Rotterdam, 3015 GJ
Rob Pieters, MD, MSC, PhD, 31-88-97 26003, rpieters@prinsesmaximacentrum.nl
United Kingdom1 site, 1 recruiting
- Recruiting
Great Ormond Street Hospital for Children
London, England, WC1N 3JH
Phil Ancliff, MD, 44-20-7829-8831
About this study
Official title: International Collaborative Treatment Protocol for Infants Under One Year With Acute Lymphoblastic or Biphenotypic Leukemia
RATIONALE: Giving chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine, methotrexate, leucovorin, and antithymocyte globulin before and after transplant may stop this from happening. It is not yet known which treatment regimen is most effective in treating acute leukemia.
PURPOSE: This randomized clinical trial is studying how well different therapies work in treating infants with newly diagnosed acute leukemia.
Read the detailed description
OBJECTIVES:
Primary
- To compare an early intensification regimen comprising two "acute myeloid leukemia" induction therapy blocks with a standard protocol IB regimen administered directly after induction therapy in medium-risk (MR) and high-risk (HR) patients with newly diagnosed acute lymphoblastic or biphenotypic leukemia.
Secondary
- To compare through a randomized study the role of these regimens in treating these patients.
- To compare the overall outcome of the Interfant-06 study with outcomes in the historical control series, especially in the Interfant-99 study.
- To compare the outcomes of low-risk, MR, or HR patients in this study with those of patients in the historical control series Interfant-99 study.
- To study which factors have independent prognostic value in patients treated with these regimens.
- To assess the role of stem cell transplantation in HR patients.
OUTLINE: This is a multicenter study.
- Induction therapy:
- Prednisone phase: Patients receive prednisone orally or IV three times daily on days 1-7 and methotrexate (MTX) and prednisolone (PRDL) intrathecally (IT) on day 1. Patients then proceed to remission induction therapy.
- Remission induction phase: Patients receive dexamethasone (DEXA) IV or orally three times daily on days 8-28 followed by a taper to 0 over 1 week; vincristine (VCR) IV on days 8, 15, 22, and 29; cytarabine (ARA-C) IV over 30 minutes on days 8-21; daunorubicin hydrochloride (DNR) IV over 1 hour on days 8 and 9; asparaginase (ASP) IV over 1 hour or intramuscularly (IM) on days 15, 18, 22, 25, 29, and 33; MTX IT on days 1 and 29*; and ARA-C IT on day 15. Patients also receive PRDL or therapeutic hydrocortisone (HC) IT on days 1, 15, and 29.
NOTE: *Patients with CNS involvement at initial diagnosis also receive MTX IT on days 8 and 22. If CNS leukemia is still present at day 29, then patients receive weekly MTX IT until the CNS is free of leukemia.
After completion of induction therapy, patients are stratified according to risk group (low-risk [LR] vs medium-risk [MR] vs high-risk [HR]). Patients with low-risk disease are assigned to treatment arm I. Patients with MR or HR disease that is in complete remission (CR) on day 33 are randomized to 1 of 2 treatment arms. These patients are stratified according to status (MR with rearranged MLL vs MR with unknown MLL vs HR).
- Arm I (standard therapy):
- Protocol IB therapy (beginning on day 36 of induction therapy): Patients receive cyclophosphamide (CPM) IV over 1 hour on days 1 and 29 and oral mercaptopurine (MP) on days 1-28; ARA-C IV on days 3-6, 10-13, 17-20, and 24-27; ARA-C IT on day 10; and MTX IT on day 24. Patients also receive PRDL or therapeutic HC IT on days 10 and 24.
- MARMA therapy:
- Part I: Patients receive oral MP once daily on days 1-14; high-dose (HD) MTX IV over 24 hours on days 1 and 8; leucovorin calcium orally or IV at 42, 48, and 54 hours after each dose of MTX until MTX plasma levels are safe; and MTX IT on days 2 and 9. Patients also receive PRDL or therapeutic HC IT on days 2 and 9.
- Part II: Patients receive HD ARA-C IV over 3 hours twice daily with 12-hour intervals on days 15, 16, 22, and 23; and pegaspargase (PEG-ASP) IV over 1 hour or IM on day 23.
- OCTADA(D) reinduction therapy:
- Part I: At least 2 weeks after the completion of MARMA chemotherapy, patients receive oral dexamethasone (DEXA) three times daily on days 1-14, followed by a taper to 0 at day 21; oral thioguanine (TG) once daily on days 1-28; VCR IV on days 1, 8, 15, and 22; DNR IV over 1 hour on days 1, 8, 15, and 22; PEG-ASP IV over 1 hour or IM on day 1; ARA-C IV on days 2-5, 9-12, 16-19, and 23-26; and ARA-C IT on days 1 and 15. Patients also receive PRDL or therapeutic HC IT on days 1 and 15.
- Part II: Patients receive oral TG once daily on days 36-49; ARA-C IV once daily on days 37-40 and 45-48; and CPM IV over 1 hour on days 36 and 49.
- Maintenance therapy: At least 2 weeks after completion of the last course of OCTADA(D) chemotherapy, patients receive oral MP once daily; oral MTX once weekly; MTX IT in weeks 1 and 15; and ARA-C IT in week 8. Patients also receive PRDL or therapeutic HC IT in weeks 1, 8, and 15. Treatment continues for up to 104 weeks after initial diagnosis in the absence of disease progression or unacceptable toxicity.
- Arm II (experimental therapy):
- ADE therapy (beginning on day 36 of induction therapy: Patients receive ARA-C IV every 12 hours on days 1-10; DNR IV over 1 hour on days 1, 3, and 5; etoposide (VP-16) IV over 4 hours on days 1-5; and ARA-C IT on day 1. Patients also receive PRDL or therapeutic HC IT on day 1.
- MAE therapy: Patients receive ARA-C IV every 12 hours on days 1-10; mitoxantrone hydrochloride IV over 1 hour on days 1, 3, and 5; VP-16 IV over 4 hours on days 1-5; and MTX IT on day 1. Patients also receive PRDL or therapeutic HC IT on day 1.
- MARMA therapy:
- Part I: Patients receive oral MP once daily on days 1-14; high-dose (HD) MTX IV over 24 hours on days 1 and 8; leucovorin calcium orally or IV at 42, 48, and 54 hours after each dose of MTX until MTX plasma levels are safe; and MTX IT on days 2 and 9. Patients also receive PRDL or therapeutic HC IT on days 2 and 9.
- Part II: Patients receive HD ARA-C IV over 3 hours twice daily with 12-hour intervals on days 15, 16, 22, and 23; and pegaspargase (PEG-ASP) IV over 1 hour or IM on day 23.
- OCTADA reinduction therapy:
- Part I: At least 2 weeks after the completion of MARMA chemotherapy, patients receive oral DEXA three times daily on days 1-14, followed by a taper to 0 at day 21; oral TG once daily on days 1-28; VCR IV on days 1, 8, 15, and 22; PEG-ASP IV over 1 hour or IM on day 1; ARA-C IV on days 2-5, 9-12, 16-19, and 23-26; and ARA-C IT on days 1 and 15. Patients also receive PRDL or therapeutic HC IT on days 1 and 15.
- Part II: Beginning 1 week after completion of part I, patients receive oral TG once daily on days 36-49; ARA-C IV once daily on days 37-40 and 45-48; and CPM IV over 1 hour on days 36 and 49.
- Maintenance therapy: At least 2 weeks after completion of the last course of OCTADA chemotherapy, patients receive oral MP once daily; oral MTX once weekly; MTX IT in weeks 1 and 15; and ARA-C IT in week 8. Patients also receive PRDL or therapeutic HC IT in weeks 1, 8, and 15. Treatment continues for up to 104 weeks after initial diagnosis in the absence of disease progression or unacceptable toxicity.
All HR patients with a suitably matched donor are scheduled for allogeneic stem cell transplantation (SCT) after MARMA or before or during OCTADA(D) chemotherapy, provided they are in CR1 and no more than 8 months have elapsed since initial diagnosis.
- Conditioning regimens for allogeneic SCT:
- Matched sibling donor (MSD): Patients receive oral busulfan (BU) every 6 hours on days -7 to -4; CPM IV over 1 hour on days -3 to -2; and melphalan (MEL) IV over 1 hour on day -1.
- Matched donors (MD): Patients receive oral BU every 6 hours on days -7 to -4; CPM IV over 1 hour on days -3 to -2; MEL IV over 1 hour on day -1; and anti-thymocyte globulin (ATG) IV over 4 hours on days -3 to -1.
- Graft-Versus-Host Disease (GVHD) prophylaxis and therapy:
- MSD: Patients receive cyclosporine (CsA) IV or orally twice daily beginning on day -1 and continuing to day 60 after SCT, followed by a taper in the absence of GVHD symptoms.
- MD: Patients receive CsA as in group MSD; MTX IV on days 1, 3, and 6; leucovorin calcium IV on days 2, 4, and 7; and ATG IV on days -3 to -1.
- Allogeneic SCT: Patients undergo infusion of bone marrow, peripheral blood, or cord blood hematopoietic stem cells on day 0.
After completion of study therapy, patients are followed periodically for up to 2 years.
- Conditions
- Leukemia
- Being tested
- anti-thymocyte globulin, asparaginase, busulfan, cyclophosphamide, cyclosporine
- Keywords
- untreated childhood acute lymphoblastic leukemia, T-cell childhood acute lymphoblastic leukemia, acute undifferentiated leukemia
- Medical subject headings
- Leukemia, Leukemia, Biphenotypic, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-thymocyte globulinBiological
asparaginaseDrug
busulfanDrug
cyclophosphamideDrug
cyclosporineDrug
cytarabineDrug
daunorubicin hydrochlorideDrug
etoposideDrug
melphalanDrug
mercaptopurineDrug
methotrexateDrug
mitoxantrone hydrochlorideDrug
pegaspargaseDrug
prednisoloneDrug
prednisoneDrug
therapeutic hydrocortisoneDrug
thioguanineDrug
allogeneic bone marrow transplantationProcedure or surgery
allogeneic hematopoietic stem cell transplantationProcedure or surgery
umbilical cord blood transplantationProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-free survival
Secondary outcomes (3)
Survival
Event-free survival
Event-free survival within each risk group (i.e., low-risk, medium-risk, or high-risk)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2007 (estimated)
- Study startJan 2006
- Primary completionDec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 445 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Dutch Childhood Oncology Group
- Sponsor type
- University, hospital or other
- Collaborators
- BFM Germany, CORS Monza Italy, Associazione Italiana Ematologia Oncologia Pediatrica, Australian and New Zealand Children's Oncology Group, BFM Austria, CLCG France Belgium Portugal, COALL Germany, CPH, Czech republic, DFCI consortium USA, FRALLE France, Hong Kong Government, MD Anderson USA, NOPHO Scandinavian countries, PINDA, Chile, PPLLSG Poland, Seattle USA, SJCRH USA, UKCCSG United Kingdom
- Responsible party
- Sponsor
- Investigators
- Rob Pieters, MD, MSC, PhD, Study chair, Prinses Maxima Centrum voor kinderoncologie UtrechtMartin Schrappe, MD, PhD, Study chair, University Hospital Schleswig-Holstein
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00550992
- Sponsor's protocol ID
- CDR0000570260
- Other IDs
- DCOG-INTERFANT-06, EUDRACT-2005-004599-19, CCLG-LK-2006-10
- Acronym
- Interfant06
- Status last verified
- Feb 2019
- First submitted
- 22 Oct 2007
- Last updated
- 30 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Stutterheim J, van der Sluis IM, de Lorenzo P, Alten J, Ancliffe P, Attarbaschi A, Brethon B, Biondi A, Campbell M, Cazzaniga G, Escherich G, Ferster A, Kotecha RS, Lausen B, Li CK, Lo Nigro L, Locatelli F, Marschalek R, Meyer C, Schrappe M, Stary J, Vora A, Zuna J, van der Velden VHJ, Szczepanski T, Valsecchi MG, Pieters R. Clinical Implications of Minimal Residual Disease Detection in Infants With KMT2A-Rearranged Acute Lymphoblastic Leukemia Treated on the Interfant-06 Protocol. J Clin Oncol. 2021 Feb 20;39(6):652-662. doi: 10.1200/JCO.20.02333. Epub 2021 Jan 6.
PubMed 33405950Pieters R, De Lorenzo P, Ancliffe P, Aversa LA, Brethon B, Biondi A, Campbell M, Escherich G, Ferster A, Gardner RA, Kotecha RS, Lausen B, Li CK, Locatelli F, Attarbaschi A, Peters C, Rubnitz JE, Silverman LB, Stary J, Szczepanski T, Vora A, Schrappe M, Valsecchi MG. Outcome of Infants Younger Than 1 Year With Acute Lymphoblastic Leukemia Treated With the Interfant-06 Protocol: Results From an International Phase III Randomized Study. J Clin Oncol. 2019 Sep 1;37(25):2246-2256. doi: 10.1200/JCO.19.00261. Epub 2019 Jul 8.
PubMed 31283407
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- International Collaborative Treatment Protocol for Infants Under One Year With Acute Lymphoblastic or Biphenotypic Leukemia
- ClinicalTrials.gov ID
- NCT00550992
- Acronym / sponsor ID
- Interfant06 / CDR0000570260
- Conditions
- Leukemia
- Keywords
- untreated childhood acute lymphoblastic leukemia, T-cell childhood acute lymphoblastic leukemia, acute undifferentiated leukemia
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 445 participants (estimated)
- Lead sponsor
- Dutch Childhood Oncology GroupUniversity, hospital or other
- Collaborators
- BFM Germany, CORS Monza Italy, Associazione Italiana Ematologia Oncologia Pediatrica, Australian and New Zealand Children's Oncology Group, BFM Austria, CLCG France Belgium Portugal, COALL Germany, CPH, Czech republic, DFCI consortium USA, FRALLE France, Hong Kong Government, MD Anderson USA, NOPHO Scandinavian countries, PINDA, Chile, PPLLSG Poland, Seattle USA, SJCRH USA, UKCCSG United Kingdom
- Study start
- Jan 2006 (actual)
- Primary completion
- Dec 2020 (estimated)
- First posted
- 30 Oct 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Giving chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine, methotrexate, leucovorin, and antithymocyte globulin before and after transplant may stop this from happening. It is not yet known which treatment regimen is most effective in treating acute leukemia.
PURPOSE: This randomized clinical trial is studying how well different therapies work in treating infants with newly diagnosed acute leukemia.
Detailed description
OBJECTIVES:
Primary
- To compare an early intensification regimen comprising two "acute myeloid leukemia" induction therapy blocks with a standard protocol IB regimen administered directly after induction therapy in medium-risk (MR) and high-risk (HR) patients with newly diagnosed acute lymphoblastic or biphenotypic leukemia.
Secondary
- To compare through a randomized study the role of these regimens in treating these patients.
- To compare the overall outcome of the Interfant-06 study with outcomes in the historical control series, especially in the Interfant-99 study.
- To compare the outcomes of low-risk, MR, or HR patients in this study with those of patients in the historical control series Interfant-99 study.
- To study which factors have independent prognostic value in patients treated with these regimens.
- To assess the role of stem cell transplantation in HR patients.
OUTLINE: This is a multicenter study.
- Induction therapy:
- Prednisone phase: Patients receive prednisone orally or IV three times daily on days 1-7 and methotrexate (MTX) and prednisolone (PRDL) intrathecally (IT) on day 1. Patients then proceed to remission induction therapy.
- Remission induction phase: Patients receive dexamethasone (DEXA) IV or orally three times daily on days 8-28 followed by a taper to 0 over 1 week; vincristine (VCR) IV on days 8, 15, 22, and 29; cytarabine (ARA-C) IV over 30 minutes on days 8-21; daunorubicin hydrochloride (DNR) IV over 1 hour on days 8 and 9; asparaginase (ASP) IV over 1 hour or intramuscularly (IM) on days 15, 18, 22, 25, 29, and 33; MTX IT on days 1 and 29*; and ARA-C IT on day 15. Patients also receive PRDL or therapeutic hydrocortisone (HC) IT on days 1, 15, and 29.
NOTE: *Patients with CNS involvement at initial diagnosis also receive MTX IT on days 8 and 22. If CNS leukemia is still present at day 29, then patients receive weekly MTX IT until the CNS is free of leukemia.
After completion of induction therapy, patients are stratified according to risk group (low-risk [LR] vs medium-risk [MR] vs high-risk [HR]). Patients with low-risk disease are assigned to treatment arm I. Patients with MR or HR disease that is in complete remission (CR) on day 33 are randomized to 1 of 2 treatment arms. These patients are stratified according to status (MR with rearranged MLL vs MR with unknown MLL vs HR).
- Arm I (standard therapy):
- Protocol IB therapy (beginning on day 36 of induction therapy): Patients receive cyclophosphamide (CPM) IV over 1 hour on days 1 and 29 and oral mercaptopurine (MP) on days 1-28; ARA-C IV on days 3-6, 10-13, 17-20, and 24-27; ARA-C IT on day 10; and MTX IT on day 24. Patients also receive PRDL or therapeutic HC IT on days 10 and 24.
- MARMA therapy:
- Part I: Patients receive oral MP once daily on days 1-14; high-dose (HD) MTX IV over 24 hours on days 1 and 8; leucovorin calcium orally or IV at 42, 48, and 54 hours after each dose of MTX until MTX plasma levels are safe; and MTX IT on days 2 and 9. Patients also receive PRDL or therapeutic HC IT on days 2 and 9.
- Part II: Patients receive HD ARA-C IV over 3 hours twice daily with 12-hour intervals on days 15, 16, 22, and 23; and pegaspargase (PEG-ASP) IV over 1 hour or IM on day 23.
- OCTADA(D) reinduction therapy:
- Part I: At least 2 weeks after the completion of MARMA chemotherapy, patients receive oral dexamethasone (DEXA) three times daily on days 1-14, followed by a taper to 0 at day 21; oral thioguanine (TG) once daily on days 1-28; VCR IV on days 1, 8, 15, and 22; DNR IV over 1 hour on days 1, 8, 15, and 22; PEG-ASP IV over 1 hour or IM on day 1; ARA-C IV on days 2-5, 9-12, 16-19, and 23-26; and ARA-C IT on days 1 and 15. Patients also receive PRDL or therapeutic HC IT on days 1 and 15.
- Part II: Patients receive oral TG once daily on days 36-49; ARA-C IV once daily on days 37-40 and 45-48; and CPM IV over 1 hour on days 36 and 49.
- Maintenance therapy: At least 2 weeks after completion of the last course of OCTADA(D) chemotherapy, patients receive oral MP once daily; oral MTX once weekly; MTX IT in weeks 1 and 15; and ARA-C IT in week 8. Patients also receive PRDL or therapeutic HC IT in weeks 1, 8, and 15. Treatment continues for up to 104 weeks after initial diagnosis in the absence of disease progression or unacceptable toxicity.
- Arm II (experimental therapy):
- ADE therapy (beginning on day 36 of induction therapy: Patients receive ARA-C IV every 12 hours on days 1-10; DNR IV over 1 hour on days 1, 3, and 5; etoposide (VP-16) IV over 4 hours on days 1-5; and ARA-C IT on day 1. Patients also receive PRDL or therapeutic HC IT on day 1.
- MAE therapy: Patients receive ARA-C IV every 12 hours on days 1-10; mitoxantrone hydrochloride IV over 1 hour on days 1, 3, and 5; VP-16 IV over 4 hours on days 1-5; and MTX IT on day 1. Patients also receive PRDL or therapeutic HC IT on day 1.
- MARMA therapy:
- Part I: Patients receive oral MP once daily on days 1-14; high-dose (HD) MTX IV over 24 hours on days 1 and 8; leucovorin calcium orally or IV at 42, 48, and 54 hours after each dose of MTX until MTX plasma levels are safe; and MTX IT on days 2 and 9. Patients also receive PRDL or therapeutic HC IT on days 2 and 9.
- Part II: Patients receive HD ARA-C IV over 3 hours twice daily with 12-hour intervals on days 15, 16, 22, and 23; and pegaspargase (PEG-ASP) IV over 1 hour or IM on day 23.
- OCTADA reinduction therapy:
- Part I: At least 2 weeks after the completion of MARMA chemotherapy, patients receive oral DEXA three times daily on days 1-14, followed by a taper to 0 at day 21; oral TG once daily on days 1-28; VCR IV on days 1, 8, 15, and 22; PEG-ASP IV over 1 hour or IM on day 1; ARA-C IV on days 2-5, 9-12, 16-19, and 23-26; and ARA-C IT on days 1 and 15. Patients also receive PRDL or therapeutic HC IT on days 1 and 15.
- Part II: Beginning 1 week after completion of part I, patients receive oral TG once daily on days 36-49; ARA-C IV once daily on days 37-40 and 45-48; and CPM IV over 1 hour on days 36 and 49.
- Maintenance therapy: At least 2 weeks after completion of the last course of OCTADA chemotherapy, patients receive oral MP once daily; oral MTX once weekly; MTX IT in weeks 1 and 15; and ARA-C IT in week 8. Patients also receive PRDL or therapeutic HC IT in weeks 1, 8, and 15. Treatment continues for up to 104 weeks after initial diagnosis in the absence of disease progression or unacceptable toxicity.
All HR patients with a suitably matched donor are scheduled for allogeneic stem cell transplantation (SCT) after MARMA or before or during OCTADA(D) chemotherapy, provided they are in CR1 and no more than 8 months have elapsed since initial diagnosis.
- Conditioning regimens for allogeneic SCT:
- Matched sibling donor (MSD): Patients receive oral busulfan (BU) every 6 hours on days -7 to -4; CPM IV over 1 hour on days -3 to -2; and melphalan (MEL) IV over 1 hour on day -1.
- Matched donors (MD): Patients receive oral BU every 6 hours on days -7 to -4; CPM IV over 1 hour on days -3 to -2; MEL IV over 1 hour on day -1; and anti-thymocyte globulin (ATG) IV over 4 hours on days -3 to -1.
- Graft-Versus-Host Disease (GVHD) prophylaxis and therapy:
- MSD: Patients receive cyclosporine (CsA) IV or orally twice daily beginning on day -1 and continuing to day 60 after SCT, followed by a taper in the absence of GVHD symptoms.
- MD: Patients receive CsA as in group MSD; MTX IV on days 1, 3, and 6; leucovorin calcium IV on days 2, 4, and 7; and ATG IV on days -3 to -1.
- Allogeneic SCT: Patients undergo infusion of bone marrow, peripheral blood, or cord blood hematopoietic stem cells on day 0.
After completion of study therapy, patients are followed periodically for up to 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- Up to 1 year
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (24 listed)
- Diagnosis of acute lymphoblastic leukemia (ALL) or biphenotypic leukemia meeting the following criteria:
- Must have MLL gene rearrangements documented by split-signal fluorescence in situ hybridization and meets 1 of the following risk criteria:
- Minimum donor and stem cell requirements for high-risk patients undergoing stem cell transplantation:
- CNS or testicular leukemia at diagnosis allowed
Key exclusion criteria (8 listed)
- Mature B-ALL, defined by the immunophenotypical presence of surface immunoglobulins or t(8;14) and breakpoint as in B-ALL
- Presence of the t(9;22) (q34;q11) or bcr-abl fusion in the leukemic cells (if data are not known, patient still may be eligible)
- Relapsed ALL
- See Disease Characteristics
- More than 4 weeks since prior systemic corticosteroids
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 |
|---|---|---|
| anti-thymocyte globulin | Biological | – |
| asparaginase | Drug | – |
| busulfan | Drug | – |
| cyclophosphamide | Drug | – |
| cyclosporine | Drug | – |
| cytarabine | Drug | – |
| daunorubicin hydrochloride | Drug | – |
| etoposide | Drug | – |
| leucovorin calcium | Drug | – |
| melphalan | Drug | – |
| mercaptopurine | Drug | – |
| methotrexate | Drug | – |
| mitoxantrone hydrochloride | Drug | – |
| pegaspargase | Drug | – |
| prednisolone | Drug | – |
| prednisone | Drug | – |
| therapeutic hydrocortisone | Drug | – |
| thioguanine | Drug | – |
| vincristine sulfate | Drug | – |
| allogeneic bone marrow transplantation | Procedure or surgery | – |
| allogeneic hematopoietic stem cell transplantation | Procedure or surgery | – |
| umbilical cord blood transplantation | Procedure or surgery | – |
Primary outcome
Disease-free survival
3 secondary outcomes
Survival
Event-free survival
Event-free survival within each risk group (i.e., low-risk, medium-risk, or high-risk)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2019.
- Derived from this study: PubMed 33405950Stutterheim J, van der Sluis IM, de Lorenzo P, Alten J, Ancliffe P, Attarbaschi A, Brethon B, Biondi A, Campbell M, Cazzaniga G, Escherich G, Ferster A, Kotecha RS, Lausen B, Li CK, Lo Nigro L, Locatelli F, Marschalek R, Meyer C, Schrappe M, Stary J, Vora A, Zuna J, van der Velden VHJ, Szczepanski T, Valsecchi MG, Pieters R. Clinical Implications of Minimal Residual Disease Detection in Infants With KMT2A-Rearranged Acute Lymphoblastic Leukemia Treated on the Interfant-06 Protocol. J Clin Oncol. 2021 Feb 20;39(6):652-662. doi: 10.1200/JCO.20.02333. Epub 2021 Jan 6.
- Derived from this study: PubMed 31283407Pieters R, De Lorenzo P, Ancliffe P, Aversa LA, Brethon B, Biondi A, Campbell M, Escherich G, Ferster A, Gardner RA, Kotecha RS, Lausen B, Li CK, Locatelli F, Attarbaschi A, Peters C, Rubnitz JE, Silverman LB, Stary J, Szczepanski T, Vora A, Schrappe M, Valsecchi MG. Outcome of Infants Younger Than 1 Year With Acute Lymphoblastic Leukemia Treated With the Interfant-06 Protocol: Results From an International Phase III Randomized Study. J Clin Oncol. 2019 Sep 1;37(25):2246-2256. doi: 10.1200/JCO.19.00261. Epub 2019 Jul 8.
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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.
Rob Pieters, MD, MSC, PhD study chair
Prinses Maxima Centrum voor kinderoncologie Utrecht
Martin Schrappe, MD, PhD study chair
University Hospital Schleswig-Holstein
13 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing anti-thymocyte globulin, asparaginase and busulfan in people with Leukemia, run by Dutch Childhood Oncology Group at 13 sites in 9 countries.
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 24 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 30 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, Germany, Austria, Belgium, Czechia and 4 more countries. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease-free survival. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00550992, which also lists 2 linked publications.
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 30 Jul 2019.