An Early Phase 1 interventional study of Hyper-CVAD and Sirolimus in Lymphoid Malignancies (New or Relapsed), Acute Lymphoblastic Leukemia and Burkitt Lymphoma, sponsored by Sidney Kimmel Cancer Center at Thomas Jefferson University. Completed at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-05-04.
Sponsored by Sidney Kimmel Cancer Center at Thomas Jefferson University · Early Phase 1, Interventional, and Treatment
This is a pilot study, assessing the feasibility, safety and toxicity of an mTOR (mammalian target of Rapamycin) inhibitor (MTI), rapamycin, when administered with HyperCVAD (Hyperfractionated Cyclophosphamide, Vincristine, Doxorubicine and Dexamethasone), with an ultimate goal to perform a phase II study to evaluate response rates and survival in adults with Acute Lymphoblastic Leukemia (ALL) and aggressive lymphoid malignancies.
The primary objective of this trial is to characterize the feasibility, safety and tolerability of therapy with Hyper-CVAD and Rapamycin in adults with ALL and other aggressive lymphoid malignancies.
This study will evaluate the effectiveness of Rapamycin given in combination with Hyper-CVAD during A treatment cycles, and Methotrexate and Cytarabine in B treatment cycles. Both cycles will also contain the drug Rituximab if the patient has a B cell type of leukemia or lymphoma.
This combination of drugs are being studied to determine whether or not these drugs will have an effect in treating this disease.
Current therapeutic regimens for induction of remission in ALL are broadly similar. There is no single best regimen for induction therapy. The hyper-CVAD regimen is of particular interest because it does not include asparaginase as part of the therapeutic regimen and the results of induction are similar to other published regimens.
The HyperCVAD regimen with or without rituximab is also an accepted induction regimen for lymphoblastic lymphoma, Burkitt and Burkitt like lymphoma, Mantle Cell Lymphoma, and ALL in the elderly. The regimen has also been used as a salvage regimen in patients with the above diagnoses who have relapsed after another induction regimen.
This trial will add a novel agent, an mTOR inhibitor (MTI), rapamycin, to act synergistically with the HyperCVAD regimen. This is a pilot study, assessing the feasibility, safety and toxicity of this regimen, with an ultimate goal to perform a phase II study to evaluate response rates and survival.
This is a pilot study of the Hyper-CVAD regimen with Rapamycin for the treatment of adults with acute lymphoblastic leukemia or other aggressive lymphoid malignancies. The standard Hyper-CVAD regimen will be used, with the addition of the investigational agent, Rapamycin. Hyper-CVAD alone is one of the current standard induction and salvage regimens used to treat ALL and other aggressive lymphoid malignancies.
Subjects included will have either de novo, relapsed, or refractory ALL or another aggressive lymphoid malignancy.
Chemotherapy will consist of 4 'A' cycles alternating with 4 'B' cycles, every 21 days, or as count recovery allows (at least 14 days apart) as follows: 1A; 1B; 2A; 2B, 3A; 3B; 4A; 4B. This is dependent on white blood cell count recovery.
2,584 studies on the registry are indexed under Precursor Cell Lymphoblastic Leukemia-Lymphoma; 473 are open to participants now.
This study's enrollment of 7 is below the median of 40 across 1,952 interventional studies indexed under Precursor Cell Lymphoblastic Leukemia-Lymphoma.
Browse Precursor Cell Lymphoblastic Leukemia-Lymphoma studies →Sidney Kimmel Cancer Center at Thomas Jefferson University is the lead sponsor of 120 studies on the registry; none are open to participants now.
Of its 23 completed or terminated interventional studies of FDA-regulated products, 7 (30%) have results posted.
Compared within Precursor Cell Lymphoblastic Leukemia-Lymphoma, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Recurrence. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Patients must have a diagnosis of one of the following lymphoid (new or ):
Exclusion Criteria:
Patients taking any of the following drugs while on-study are not eligible:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hyper-CVAD and Sirolimus
Drug: Hyper-CVAD · Drug: Sirolimus
* Cycle A: Cyclophosphamide 300mg/m2 every 12 hours on days 3-5; Vincristine 2mg/day on days 6 and 13; Doxorubicin 50mg/m2 on day 6; Decadron 40mg/ day po on days 3-6 and 13-16; Methotrexate 12mg IT on day 4; Ara-C 100mg IT on day 9. * Cycle B: Methotrexate 1000mg/m2 on day 3; Leucovorin 50mg every 6 hours starting 24 hours from the beginning of the MTX infusion until MTX levels are \< 0.1 umol/L; Ara-C 3000mg/m2 every 12 hours on days 4 and 5; Methotrexate 12mg IT on day 4; Ara-C 100mg IT on day 9. * Rituximab (if given) will be 375 mg/m2 on Days 3 and 13 of Cycle A and on Days 4 and 9 of cycle B, for a total of 8 doses over the first 4 courses.
Also known as: Cytoxan, Endoxan, Neosar, Procytox, Revimmune, Cytophosphane, Oncovin, Leurocristine, Adriamycin, Hydroxydaunorubicin, MTX, Amethopterin
Sirolimus loading dose of 12mg on day 1 followed by a single daily dose of 4 mg/ day on days 2 through 7 (Cycle A) and on days 2 through 6 (Cycle B)
Also known as: Rapamycin
Number of Participants With Count Recovery That Allows for Starting a Phase II Study to Evaluate Response Rates and Survival
This will be assessed by evaluating the tolerability of this regimen compared to historical controls who received Hyper-CVAD or Hyper-CVAD/ Rituximab regimens. The treatment will be designated feasible for an individual subject if in 80% of chemotherapy cycles the subject has count recovery that allows for starting the subsequent cycle by Day 28. Count recovery is defined as ANC (absolute neutrophil count) of \> 0.5 x 10\^9/L and platelet count \> 50 x 10\^9/L. Hyper-CVAD/Rapamycin will be deemed acceptable if it is feasible to administer in 80% or more of subjects.
Time frame: 18 months
Induction Mortality
Induction mortality. Hyper-CVAD/ Rapamycin will be considered acceptable if induction mortality does not exceed 31% in patients older than 60, or 15% in those younger than 60
Time frame: 18 months
Complete Response
To describe response rates to hyper-CVAD and sirolimus in adults with ALL and other aggressive lymphoid malignancies. Bone marrow (\<5% blasts) with adequate bone marrow cellularity, no evidence of circulating blasts or extramedullary disease and normalization of peripheral blood counts except for platelets (neutrophil count =1,000/µL).
Time frame: Every 21 days or as count recovery allows (at least 14 days apart) up to 24 weeks
| Milestone | Hyper-CVAD and Sirolimus |
|---|---|
| Started | 7 |
| Completed | 7 |
| Not completed | 0 |
This will be assessed by evaluating the tolerability of this regimen compared to historical controls who received Hyper-CVAD or Hyper-CVAD/ Rituximab regimens. The treatment will be designated feasible for an individual subject if in 80% of chemotherapy cycles the subject has count recovery that allows for starting the subsequent cycle by Day 28. Count recovery is defined as ANC (absolute neutrophil count) of \> 0.5 x 10\^9/L and platelet count \> 50 x 10\^9/L. Hyper-CVAD/Rapamycin will be deemed acceptable if it is feasible to administer in 80% or more of subjects.
| participants | Hyper-CVAD and Sirolimus |
|---|---|
| Number of Participants With Count Recovery That Allows for Starting a Phase II Study to Evaluate Response Rates and Survival | 7 |
Induction mortality. Hyper-CVAD/ Rapamycin will be considered acceptable if induction mortality does not exceed 31% in patients older than 60, or 15% in those younger than 60
Results for this outcome have not been posted.
To describe response rates to hyper-CVAD and sirolimus in adults with ALL and other aggressive lymphoid malignancies. Bone marrow (\<5% blasts) with adequate bone marrow cellularity, no evidence of circulating blasts or extramedullary disease and normalization of peripheral blood counts except for platelets (neutrophil count =1,000/µL).
| participants | Hyper-CVAD and Sirolimus |
|---|---|
| Complete Response | 4 |
Non-serious events are listed at a 1% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Hyper-CVAD and Sirolimus | — | 6/7 (85.7%) | 7/7 (100%) |
| Event | Hyper-CVAD and Sirolimus |
|---|---|
| Febrile neutropeniaBlood and lymphatic system disorders | 5/7 |
| InfectionInfections and infestations | 2/7 |
| HypotensionBlood and lymphatic system disorders | 2/7 |
| EdemaSkin and subcutaneous tissue disorders | 1/7 |
| FeverGeneral disorders | 1/7 |
| AtaxiaNervous system disorders | 1/7 |
| Speech impairmentGeneral disorders | 1/7 |
| Gram negative sepsisImmune system disorders | 1/7 |
| Face painGeneral disorders | 1/7 |
| Shortness of breathRespiratory, thoracic and mediastinal disorders | 1/7 |
| Event | Hyper-CVAD and Sirolimus |
|---|---|
| FatigueGeneral disorders | 7/7 |
| WeaknessGeneral disorders | 7/7 |
| NauseaGeneral disorders | 6/7 |
| RashSkin and subcutaneous tissue disorders | 6/7 |
| EdemaSkin and subcutaneous tissue disorders | 5/7 |
| TachycardiaCardiac disorders | 5/7 |
| ChillsGeneral disorders | 5/7 |
| Shortness of breathRespiratory, thoracic and mediastinal disorders | 5/7 |
| FeverGeneral disorders | 5/7 |
| Poor appetiteGeneral disorders | 5/7 |
| Age, Categorical(Participants) | Hyper-CVAD and Sirolimus |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 6 |
| >=65 years | 1 |
| Age, Continuous(years) | Hyper-CVAD and Sirolimus |
|---|---|
| Mean | 41.68 ± 18.94 |
| Sex: Female, Male(Participants) | Hyper-CVAD and Sirolimus |
|---|---|
| Female | 2 |
| Male | 5 |
| Region of Enrollment(participants) | Hyper-CVAD and Sirolimus |
|---|---|
| United States | 7 |
This study is completed, as verified in May 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Sirolimus
Precursor Cell Lymphoblastic Leukemia-Lymphoma →
Sidney Kimmel Cancer Center at Thomas Jefferson University →