A Phase 2 interventional study of RAPA-201 Autologous T cells in Relapsed, Refractory Multiple Myeloma, sponsored by Rapa Therapeutics LLC. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-05-15.
Sponsored by Rapa Therapeutics LLC · Phase 2, Interventional, and Treatment
RAPA-201-RRMM is an open-label, single-arm, non-randomized multicenter phase II study of RAPA-201 autologous T cells in adults with relapsed, refractory multiple myeloma who have received at least three (3) prior lines.
This clinical trial evaluates autologous rapamycin-resistant Th1/Tc1 (RAPA-201) cells for therapy of relapsed, refractory multiple myeloma (RRMM). The study population of RRMM patients is defined by: relapse after ≥ 3 prior regimens; exposure to ≥ 2 proteasome inhibitors (PI) (e.g. bortezomib), ≥ 2 immunomodulatory agents (IMiD) (e.g. lenalidomide), and ≥ 1 anti-CD38 monoclonal antibody (e.g., daratumumab); and refractory status to ≥ 1 PI agent and ≥ 1 IMiD agent. The primary study objective is to determine the overall response rate, as evaluated by IMWG criteria, of RAPA-201 cells and a pentostatin-cyclophosphamide (PC) host conditioning regimen in patients with RRMM. A sample size of 22 patients was selected to determine whether RAPA-201 therapy represents an active regimen in RRMM, as defined by a response rate (≥ partial remission) consistent with a 35% rate.
Multiple myeloma (MM) is an incurable cancer characterized by clonal proliferation of plasma cells. MM is the second most common form of hematologic malignancy in the United States, with approximately 11,000 individuals dying from the disease in 2014. Due in part to the aging population, MM prevalence will dramatically increase in the next few decades. MM management has many FDA-approved options for the up-front setting, maintenance therapy, and therapy at second or third relapse. For patients with relapsed MM, therapy typically consists of triplet regimens approved by the U.S. Food and Drug Administration (FDA), including the KRd, DRd, and DPd regimens. Although triplet regimens are improved relative to prior therapies, they typically provide a progression-free survival of less than two years and cause substantial toxicities. Few standard, effective options exist for patients with MM who have more advanced disease and higher levels of drug refractoriness. In contrast to drug and monoclonal antibody therapy, which are essentially non-curative, T cell therapy can cure MM, as evidenced by long- term survival in recipients of allogeneic hematopoietic cell transplantation. The promise of T cell therapy against MM is further exemplified by high response rates using gene-modified autologous CAR-T cell therapy directed against the BCMA target. However, CAR-T therapy is limited by variable tumor cell target expression, which compromises response durability leading to relapse. Furthermore, CAR-T cell products are expensive to manufacture, with the financial burden further complicated by frequent inpatient hospital monitoring and treatment of potentially lethal toxicities that include cytokine storm and neurologic damage. Thus, a great need exists to develop novel T cell therapies for RRMM that are safe, cost effective, and curative. We will evaluate one such promising candidate, namely, autologous rapamycin-resistant Th1/Tc1 cells (RAPA-201).
RAPA-201 cell therapy differs from existing approaches in several important categories. First, RAPA-201 cells are rendered rapamycin-resistant by proprietary ex vivo manufacturing that rapidly and cost effectively de- differentiates senescent patient T cells, which results in a therapeutic product enriched for the beneficial T central memory (TCM) subset and severely depleted of checkpoint inhibitory receptors that inhibit anti-cancer effects. This depth and breadth of T cell re-programming is not possible in vivo due to toxicity of pharmacologic agents, which can be rendered completely non-toxic through drug extracorporealization. Operating together, T cell rapamycin-resistance, TCM differentiation, and checkpoint removal promotes RAPA-201 T cell in vivo persistence and in vivo activity required for curative anti-tumor effects. Second, RAPA-201 cells are manufactured in a high, otherwise toxic dose of the critical anti-cancer cytokine IFN-α, which promotes a CD4+Th1 and CD8+Tc1 T cell phenotype that optimizes anti-tumor effects. Third, rapamycin-resistant T cells express a diverse T cell receptor repertoire that can address the complex biology of multiple myeloma, where tumor antigens are either not known or variable over time due to tumor genetic instability. Because polyclonal RAPA-201 T cells are capable of in vivo expansion to tumor antigens, RAPA-201 therapy can be applied not only to RRMM but also to other hematologic malignancies and common solid tumors, including lung cancer resistant to PD(L)-1 checkpoint therapy. And fourth, RAPA-201 cell therapy will be administered in combination with a novel host conditioning regimen consisting of pentostatin and low-dose, dose-adjusted cyclophosphamide (PC regimen). The PC regimen causes host lymphoid depletion while sparing host myeloid cells, thus permitting repeat therapeutic RAPA-201 cycles in the outpatient setting with reduced financial burden and without substantial neutropenia and associated opportunistic infection. As such, the PC regimen safely creates "immune space" in the RRMM patient, thereby potentiating the in vivo expansion and curative potential of RAPA-201 cells.
3,760 studies on the registry are indexed under Multiple Myeloma; 769 are open to participants now.
This study's enrollment of 15 is below the median of 41 across 3,005 interventional studies indexed under Multiple Myeloma.
Browse Multiple Myeloma studies →Rapa Therapeutics LLC is the lead sponsor of 6 studies on the registry; 3 are open to participants now.
Compared within Multiple Myeloma, 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.
Presence of secretory myeloma/, as defined by ONE of the following:
Exclusion Criteria:
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.
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.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
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.
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
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.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
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.
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
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.
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.
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.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
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.
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.
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.
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.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
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.
CTCAE grade
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
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.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
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.
Allogeneic and autologous transplant
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
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.
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.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
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.
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.
Biological: RAPA-201 Autologous T cells
Autologous rapamycin resistant Th1/Tc1 cells
Also known as: RAPA-201 cells
Overall response rate
To determine the overall response rate, as evaluated by IMWG criteria, in patients with relapse, refractory multiple myeloma (RRMM) treated with autologous RAPA-201 cells and a pentostatin-cyclophosphamide (PC) host conditioning regimen.
Time frame: One (1) year after last dose of RAPA-201 cells.
Effect of therapy on disease control
(1) To determine the effect of therapy on multiple myeloma disease control, including duration of response (DOR; time from initial tumor response to disease progression).
Time frame: One (1) year after the last dose of RAPA-201 cells.
Effect in Quality of Life
To evaluate the effect of therapy on quality of life (QOL) using the FACT-BMT survey.
Time frame: One (1) year after the last dose of RAPA-201 cells.
Immune reconstitution
Immune reconstitution of participants receiving RAPA-201 cells will be measured using flow cytometry to obtain the absolute number of circulating CD4+ and CD8+ T cells per microliter of blood.
Time frame: Screening; Day 1 of every treatment cycle; End of treatment; Day 1 of Months 1, 3, 9 and 12 of Follow-up.
Plan to share: No
No publications or documents are linked to this record.
This study is completed, as verified in May 2025. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Autologous rapamycin-resistant TH1/TC1 cells RAPA-201
Rapa Therapeutics LLC